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c5a1b1cdbf45a3cb907f4f90c4e629b0899eaca2 | wikidoc | Congener | Congener
A congener (from Latin roots meaning "born together" or "within the same race or kind") has several different meanings depending on the field in which it is used. Colloquially, it is used to mean a person or thing like another in character or action.
# Biology
In biology, congeners are organisms within the same genus. Congeners within the same geographical region can compete with one another so many adaptations can be observed that mitigate this pressure on populations
# Chemistry
In chemistry, congeners are related chemicals, e.g., a derivative or an element in the same group of the periodic table
- There are 209 congeners of polychlorinated biphenyls (PCB) as well as 209 congeners of polybrominated diphenyl ethers (PBDE).
- Congeners of oleic acids can modify cell membrane behavior protecting against tumors or having effects on blood pressure.
# Fermentation
In the alcoholic beverage industry, congener refers to impurities produced during fermentation or to metals such as zinc, added to certain sweet liqueurs in order to enhance flavor. Congeners are responsible for most of the taste, aroma, and color of alcoholic beverages. It has been suggested that these substances also contribute to the symptoms of a hangover, although the more likely cause is a more complicated mix of ethanol, dehydration, and various other factors (see hangover for a more complete list).
# Genetics
In genetics, congenic organisms are organisms with very similar genomes, except for a small fraction. For example, recombinant congenic mice strains are produced in laboratories as a tool to study genetic disease. | Congener
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A congener (from Latin roots meaning "born together" or "within the same race or kind") has several different meanings depending on the field in which it is used. Colloquially, it is used to mean a person or thing like another in character or action.
# Biology
In biology, congeners are organisms within the same genus. Congeners within the same geographical region can compete with one another so many adaptations can be observed that mitigate this pressure on populations
# Chemistry
In chemistry, congeners are related chemicals, e.g., a derivative or an element in the same group of the periodic table
- There are 209 congeners of polychlorinated biphenyls (PCB) as well as 209 congeners of polybrominated diphenyl ethers (PBDE).
- Congeners of oleic acids can modify cell membrane behavior protecting against tumors or having effects on blood pressure.
# Fermentation
In the alcoholic beverage industry, congener refers to impurities produced during fermentation or to metals such as zinc, added to certain sweet liqueurs in order to enhance flavor. Congeners are responsible for most of the taste, aroma, and color of alcoholic beverages. It has been suggested that these substances also contribute to the symptoms of a hangover, although the more likely cause is a more complicated mix of ethanol, dehydration, and various other factors (see hangover for a more complete list).
# Genetics
In genetics, congenic organisms are organisms with very similar genomes, except for a small fraction. For example, recombinant congenic mice strains are produced in laboratories as a tool to study genetic disease. | https://www.wikidoc.org/index.php/Congener | |
4c692f4616ac32cf3786f075d4df7c38568f5d33 | wikidoc | Connexin | Connexin
Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions (an entirely different family of proteins, the innexins, form gap junctions in invertebrates). Each gap junction comprises 2 hemichannels, or "connexons", which are themselves each constructed out of 6 connexin molecules. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, and proper embryonic development. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.
# Structure
Connexins are four-pass transmembrane proteins with both C and N cytoplasmic termini, a cytoplasmic loop (CL) and two extra-cellular loops, (EL-1) and (EL-2). Connexins are assembled together in groups of 6 to form hemichannels, or connexons, and two hemichannels then combine to form a gap junction. The connexin gene family is diverse, with 21 identified members in the sequenced human genome, and 20 in the mouse (19 of which are orthologous pairs). They usually weigh between 26 and 60 kDa, and have an average length of 380 amino acids. The various connexins have been observed to combine into both homomeric and heteromeric gap junctions, each of which may exhibit different functional properties including pore conductance, size selectivity, charge selectivity, voltage gating, and chemical gating.
# Nomenclature
In recent literature, connexins are most commonly named according to their molecular weights, e.g. Cx26 is the connexin protein of 26 kDa. This can lead to confusion however when connexin genes from different species are compared, e.g. human Cx36 is homologous to zebrafish Cx35. A competing nomenclature is the Gja/Gjb system, where connexins are sorted by their α and β forms, then assigned an identifying number, e.g. Gja1 corresponds to Cx43. The nomenclature of the connexin genes and proteins is currently under review by the HUGO Gene Nomenclature Committee.
# Biosynthesis and Internalization
A remarkable aspect of connexins is that they have a relatively short half life of only a few hours. The result is the presence of a dynamic cycle by which connexins are synthesized and replaced. It has been suggested that this short life span allows for more finely regulated physiological processes to take place, such as in the myometrium.
## From the Nucleus to the Membrane
As they are being translated by ribosomes, connexins are inserted into the membrane of the endoplasmic reticulum (ER) (Bennett and Zukin, 2004). It is in the ER that connexins are properly folded, yielding two extracellular loops, EL-1 and EL-2. It is also in the ER that the oligomerization of connexin molecules into hemichannels begins, a process which may continue in the UR-Golgi intermediate compartment as well. The arrangements of these hemichannels can be homotypic, heterotypic, and combined heterotypic/heteromeric.
After exiting the ER and passing through the ERGIC, the folded connexins will usually enter the cis-Golgi network. However, some connexins, such as Cx26 may be transported independent of the Golgi.
## Gap Junction Assembly
After being inserted into the plasma membrane of the cell, the hemichannels freely diffuse within the lipid bilayer. Through the aid of specific proteins, mainly cadherins, the hemichannels are able to dock with hemichannels of adjacent cells forming gap junctions. Recent studies have shown the existence of communication between adherens junctions and gap junctions, suggesting a higher level of coordination than previously thought.
# Function
Connexin gap junctions are found only in vertebrates. A functionally analogous but genetically unrelated group of proteins, the pannexins are expressed in both vertebrate and invertebrate species. The innexin proteins, invertebrate gap junction proteins, are probably pannexins. They have a similar structure, but don't share any sequence homology.
# Pathologies
# List of Connexins | Connexin
Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions (an entirely different family of proteins, the innexins, form gap junctions in invertebrates).[1] Each gap junction comprises 2 hemichannels, or "connexons", which are themselves each constructed out of 6 connexin molecules. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, and proper embryonic development. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.
# Structure
Connexins are four-pass transmembrane proteins with both C and N cytoplasmic termini, a cytoplasmic loop (CL) and two extra-cellular loops, (EL-1) and (EL-2). Connexins are assembled together in groups of 6 to form hemichannels, or connexons, and two hemichannels then combine to form a gap junction. The connexin gene family is diverse, with 21 identified members in the sequenced human genome, and 20 in the mouse (19 of which are orthologous pairs). They usually weigh between 26 and 60 kDa, and have an average length of 380 amino acids. The various connexins have been observed to combine into both homomeric and heteromeric gap junctions, each of which may exhibit different functional properties including pore conductance, size selectivity, charge selectivity, voltage gating, and chemical gating.
# Nomenclature
In recent literature, connexins are most commonly named according to their molecular weights, e.g. Cx26 is the connexin protein of 26 kDa. This can lead to confusion however when connexin genes from different species are compared, e.g. human Cx36 is homologous to zebrafish Cx35. A competing nomenclature is the Gja/Gjb system, where connexins are sorted by their α and β forms, then assigned an identifying number, e.g. Gja1 corresponds to Cx43. The nomenclature of the connexin genes and proteins is currently under review by the HUGO Gene Nomenclature Committee.
# Biosynthesis and Internalization
A remarkable aspect of connexins is that they have a relatively short half life of only a few hours.[2] The result is the presence of a dynamic cycle by which connexins are synthesized and replaced. It has been suggested that this short life span allows for more finely regulated physiological processes to take place, such as in the myometrium.
## From the Nucleus to the Membrane
As they are being translated by ribosomes, connexins are inserted into the membrane of the endoplasmic reticulum (ER) (Bennett and Zukin, 2004). It is in the ER that connexins are properly folded, yielding two extracellular loops, EL-1 and EL-2. It is also in the ER that the oligomerization of connexin molecules into hemichannels begins, a process which may continue in the UR-Golgi intermediate compartment as well.[2] The arrangements of these hemichannels can be homotypic, heterotypic, and combined heterotypic/heteromeric.
After exiting the ER and passing through the ERGIC, the folded connexins will usually enter the cis-Golgi network.[3] However, some connexins, such as Cx26 may be transported independent of the Golgi.[4][5][6][7][8]
## Gap Junction Assembly
After being inserted into the plasma membrane of the cell, the hemichannels freely diffuse within the lipid bilayer.[9] Through the aid of specific proteins, mainly cadherins, the hemichannels are able to dock with hemichannels of adjacent cells forming gap junctions.[10] Recent studies have shown the existence of communication between adherens junctions and gap junctions,[11] suggesting a higher level of coordination than previously thought.
# Function
Connexin gap junctions are found only in vertebrates. A functionally analogous but genetically unrelated group of proteins, the pannexins are expressed in both vertebrate and invertebrate species. The innexin proteins, invertebrate gap junction proteins, are probably pannexins. They have a similar structure, but don't share any sequence homology.
# Pathologies
# List of Connexins | https://www.wikidoc.org/index.php/Connexin | |
7a906ff66be84eb456f8f58dd46b6b3f23f760cf | wikidoc | Momentum | Momentum
In classical mechanics, momentum (pl. momenta; SI unit kg·m/s, or, equivalently, N·s) is the product of the mass and velocity of an object (p=mv). For more accurate measures of momentum, see the section "modern definitions of momentum" on this page. It is sometimes referred to as linear momentum to distinguish it from the related subject of angular momentum. Linear momentum is a vector quantity, since it has a direction as well as a magnitude. Angular momentum is a pseudovector quantity because it gains an additional sign flip under an improper rotation. The total momentum of any group of objects remains the same unless outside forces act on the objects.
Momentum is a conserved quantity, meaning that the total momentum of any closed system (one not affected by external forces) cannot change.
# History of the concept
The word for the general concept of mōmentum was used in the Roman Republic primarily to mean "a movement, motion (as an indwelling force ...)." A fish was able to change velocity (velocitas) through the mōmentum of its tail. The word is formed by an accretion of suffices on the stem of Latin movēre, "to move." A movi-men- is the result of the movēre just as frag-men- is the result of frangere, "to break." Extension by -to- obtains mōvimentum and fragmentum, the former contracting to mōmentum.
The mōmentum was not merely the motion, which was mōtus, but was the power residing in a moving object, captured by today's mathematical definitions. A mōtus, "movement", was a stage in any sort of change, while velocitas, "swiftness", captured only speed. The Romans, due to limitations inherent in the Roman numeral system,Template:Clarifyme were unable to go further with the perception.
The concept of momentum in classical mechanics was originated by a number of great thinkers and experimentalists. The first of these was Ibn Sina (Avicenna) circa 1000, who referred to impetus as proportional to weight times velocity. René Descartes later referred to mass times velocity as the fundamental force of motion. Galileo in his Two New Sciences used the Italian word "impeto."
The question has been much debated as to what Sir Isaac Newton's contribution to the concept was. Apparently nothing, except to state more fully and with better mathematics what was already known. The first and second of Newton's Laws of Motion had already been stated by John Wallis in his 1670 work, Mechanica slive De Motu, Tractatus Geometricus: "the initial state of the body, either of rest or of motion, will persist" and "If the force is greater than the resistance, motion will result...." Wallis uses momentum and vis for force.
Newton's "Mathematical Principles of Natural History" when it first came out in 1686 showed a similar casting around for words to use for the mathematical momentum. His Definition II defines quantitas motus, "quantity of motion," as "arising from the velocity and quantity of matter conjointly", which identifies it as momentum. Thus when in Law II he refers to mutatio motus, "change of motion," being proportional to the force impressed, he is generally taken to mean momentum and not motion.
It remained only to assign a standard term to the quantity of motion. The first use of "momentum" in its proper mathematical sense is not clear but by the time of Jenning's Miscellanea in 1721, four years before the final edition of Newton's Principia Mathematica, momentum M or "quantity of motion" was being defined for students as "a rectangle", the product of Q and V where Q is "quantity of material" and V is "velocity", s/t.
# Linear momentum of a particle
If an object is moving in any reference frame, then it has momentum in that frame. It is important to note that momentum is frame dependent. That is, the same object may have a certain momentum in one frame of reference, but a different amount in another frame. For example, a moving object has momentum in a reference frame fixed to a spot on the ground, while at the same time having 0 momentum in a reference frame attached to the object's center of mass.
The amount of momentum that an object has depends on two physical quantities: the mass and the velocity of the moving object in the frame of reference. In physics, the usual symbol for momentum is a small bold p (bold because it is a vector); so this can be written:
where:
Example: a model airplane of 1 kg travelling due north at 1 m/s in straight and level flight has a momentum of 1 kg m/s due north measured from the ground. To the dummy pilot in the cockpit it has a velocity and momentum of zero.
According to Newton's second law the rate of change of the momentum of a particle is proportional to the resultant force acting on the particle and is in the direction of that force. In the case of constant mass, and velocities much less than the speed of light, this definition results in the equation
-r just simply
where F is understood to be the resultant.
Example: a model airplane of 1 kg accelerates from rest to a velocity of 1 m/s due north in 1 sec. The thrust required to produce this acceleration is 1 newton. The change in momentum is 1 kg-m/sec. To the dummy pilot in the cockpit there is no change of momentum. Its pressing backward in the seat is a reaction to the unbalanced thrust, shortly to be balanced by the drag.
# Linear momentum of a system of particles
## Relating to mass and velocity
The linear momentum of a system of particles is the vector sum of the momenta of all the individual objects in the system.
where
It can be shown that, in the center of mass frame the momentum of a system is zero. Additionally, the momentum in a frame of reference that is moving at a velocity vcm with respect to that frame is simply:
where:
## Relating to force- General equations of motion
The linear momentum of a system of particles can also be defined as the product of the total mass \ M of the system times the velocity of the center of mass \mathbf{v}_{cm}
This is commonly known as Newton's second law.
For a more general derivation using tensors, we consider a moving body (see Figure), assumed as a continuum, occupying a volume \ V at a time \ t, having a surface area \ S, with defined traction or surface forces \ T_i^{(n)} acting on every point of the body surface, body forces \ F_i per unit of volume on every point within the volume \ V, and a velocity field \ v_i prescribed throughout the body. Following the previous equation, The linear momentum of the system is:
By definition the stress vector is \ T_i^{(n)} =\sigma_{ij}n_j, then
Using the Gauss's divergency theorem to convert a surface integral to a volume integral gives
For an arbitrary volume the integrand vanishes, and we have the Cauchy's equations of motion
If a system is in equilibrium, the change in momentum with respect to time is equal to 0, as there is no acceleration.
-r using tensors,
These are the equilibrium equations which are used in solid mechanics for solving problems of linear elasticity.
In engineering notation, the equilibrium equations are expressed as
# Conservation of linear momentum
The law of conservation of linear momentum is a fundamental law of nature, and it states that the total momentum of a closed system of objects (which has no interactions with external agents) is constant. One of the consequences of this is that the center of mass of any system of objects will always continue with the same velocity unless acted on by a force from outside the system.
Conservation of momentum is a mathematical consequence of the homogeneity (shift symmetry) of space (position in space is the canonical conjugate quantity to momentum). So, momentum conservation can be philosophically stated as "nothing depends on location per se".
In an isolated system (one where external forces are absent) the total momentum will be constant: this is implied by Newton's first law of motion. Newton's third law of motion, the law of reciprocal actions, which dictates that the forces acting between systems are equal in magnitude, but opposite in sign, is due to the conservation of momentum.
Since position in space is a vector quantity, momentum (being the canonical conjugate of position) is a vector quantity as well - it has direction. Thus, when a gun is fired, the final total momentum of the system (the gun and the bullet) is the vector sum of the momenta of these two objects. Assuming that the gun and bullet were at rest prior to firing (meaning the initial momentum of the system was zero), the final total momentum must also equal 0.
In an isolated system with only two objects, the change in momentum of one object must be equal and opposite to the change in momentum of the other object. Mathematically,
\Delta \mathbf{p}_1 = -\Delta \mathbf{p}_2
Momentum has the special property that, in a closed system, it is always conserved, even in collisions and separations caused by explosive forces. Kinetic energy, on the other hand, is not conserved in collisions if they are inelastic. Since momentum is conserved it can be used to calculate an unknown velocity following a collision or a separation if all the other masses and velocities are known.
A common problem in physics that requires the use of this fact is the collision of two particles. Since momentum is always conserved, the sum of the momenta before the collision must equal the sum of the momenta after the collision:
where:
Usually, we either only know the velocities before or after a collision and would like to also find out the opposite. Correctly solving this problem means you have to know what kind of collision took place. There are two basic kinds of collisions, both of which conserve momentum:
- Elastic collisions conserve kinetic energy as well as total momentum before and after collision.
- Inelastic collisions don't conserve kinetic energy, but total momentum before and after collision is conserved.
### Elastic collisions
A collision between two Pool balls is a good example of an almost totally elastic collision. In addition to momentum being conserved when the two balls collide, the sum of kinetic energy before a collision must equal the sum of kinetic energy after:
Since the 1/2 factor is common to all the terms, it can be taken out right away.
In the case of two objects colliding head on we find that the final velocity
which can then easily be rearranged to
Special Case: m1>>m2
Now consider the case when the mass of one body, say m1, is far greater than that of the other, m2 (m1>>m2).
In that case m1+m2 is approximately equal to m1 and m1-m2 is approximately equal to m1.
Using these approximations, the above formula for v_{2,\mathrm{f}} reduces to v_{2,\mathrm{f}}=2v_{1,\mathrm{i}}-v_{2,\mathrm{i}}.
Its physical interpretation is that in the case of a collision between two bodies, one of which is much more massive than the other, the lighter body ends up moving in the opposite direction with twice the original speed of the more massive body.
Special Case: m1=m2
Another special case is when the collision is between two bodies of equal mass.
Say body m1 moving at velocity v1 strikes body m2 that is at rest (v2).
Putting this case in the equation derived above we will see that after the collision, the body that was moving (m1) will start moving with velocity v2 and the mass m2 will start moving with velocity v1. So there will be an exchange of velocities.
Now suppose one of the masses, say m2, was at rest. In that case after the collision the moving body, m1, will come to rest and the body that was at rest, m2, will start moving with the velocity that m1 had before the collision.
Note that all of these observations are for an elastic collision.
This phenomenon is demonstrated by Newton's cradle, one of the best known examples of conservation of momentum, a real life example of this special case.
In the case of objects colliding in more than one dimension, as in oblique collisions, the velocity is resolved into orthogonal components with one component perpendicular to the plane of collision and the other component or components in the plane of collision. The velocity components in the plane of collision remain unchanged, while the velocity perpendicular to the plane of collision is calculated in the same way as the one-dimensional case.
For example, in a two-dimensional collision, the momenta can be resolved into x and y components. We can then calculate each component separately, and combine them to produce a vector result. The magnitude of this vector is the final momentum of the isolated system.
See the elastic collision page for more details.
x=2a
### Inelastic collisions
A common example of a perfectly inelastic collision is when two snowballs collide and then stick together afterwards. This equation describes the conservation of momentum:
It can be shown that a perfectly inelastic collision is one in which the maximum amount of kinetic energy is converted into other forms. For instance, if both objects stick together after the collision and move with a final common velocity, one can always find a reference frame in which the objects are brought to rest by the collision and 100% of the kinetic energy is converted. This is true even in the relativistic case and utilized in particle accelerators to efficiently convert kinetic energy into new forms of mass-energy (i.e. to create massive particles).
In case of Inelastic collision, there is a parameter attached called coefficient of restitution (denoted by small 'e' or 'c' in many text books). It is defined as the ratio of relative velocity of separation to relative velocity of approach. It is a ratio hence it is a dimensionless quantity.
When we have an elastic collision the value of e (= coefficient of restitution) is 1, i.e. the relative velocity of approach is same as the relative velocity of separation of the colliding bodies. In an elastic collision the Kinetic energy of the system is conserved.
When a collision is not elastic (e<1) it is an inelastic collision. In case of a perfectly inelastic collision the relative velocity of separation of the centre of masses of the colliding bodies is 0. Hence after collision the bodies stick together after collision. In case of an inelastic collision the loss of Kinetic energy is maximum as stated above.
In all types of collision if no external force is acting on the system of colliding bodies, the momentum will always get preserved.
### Explosions
An explosion occurs when an object is divided into two or more fragments due to a release of energy.
Note that kinetic energy in a system of explosion is not conserved because it involves energy transformation. (i.e. kinetic energy changes into heat and sound energy)
In the exploding cannon demonstration, total system momentum is conserved. The system consists of two objects - a cannon and a tennis ball. Before the explosion, the total momentum of the system is zero since the cannon and the tennis ball located inside of it are both at rest. After the explosion, the total momentum of the system must still be zero. If the ball acquires 50 units of forward momentum, then the cannon acquires 50 units of backwards momentum. The vector sum of the individual momenta of the two objects is 0. Total system momentum is conserved.
See the inelastic collision page for more details.
# Modern definitions of momentum
## Momentum in relativistic mechanics
In relativistic mechanics, in order to be conserved, momentum must be defined as:
where
Relativistic momentum can also be written as invariant mass times the object's proper velocity, defined as the rate of change of object position in the observer frame with respect to time elapsed on object clocks (i.e. object proper time). Relativistic momentum becomes Newtonian momentum: m\mathbf{v} at low speed \big(\mathbf{v}/c \rightarrow 0 \big).
Relativistic four-momentum as proposed by Albert Einstein arises from the invariance of four-vectors under Lorentzian translation. The four-momentum is defined as:
where
The "length" of the vector is the mass times the speed of light, which is invariant across all reference frames:
Momentum of massless objects
Objects without a rest mass, such as photons, also carry momentum. The formula is:
where
Generalization of momentum
Momentum is the Noether charge of translational invariance. As such, even fields as well as other things can have momentum, not just particles. However, in curved space-time which is not asymptotically Minkowski, momentum isn't defined at all.
## Momentum in quantum mechanics
In quantum mechanics, momentum is defined as an operator on the wave function. The Heisenberg uncertainty principle defines limits on how accurately the momentum and position of a single observable system can be known at once. In quantum mechanics, position and momentum are conjugate variables.
For a single particle with no electric charge and no spin, the momentum operator can be written in the position basis as
where:
- \nabla is the gradient operator;
- \hbar is the reduced Planck constant;
- i = \sqrt{-1} is the imaginary unit.
This is a commonly encountered form of the momentum operator, though not the most general one.
## Momentum in electromagnetism
Electric and magnetic fields possess momentum regardless of whether they are static or
they change in time. It is a great surprise for freshmen who are introduced
to the well known fact of the pressure {P} of an electrostatic (magnetostatic) field upon a metal sphere,
cylindrical capacity or ferromagnetic bar:
where { W},
{\mathbf E}, {\mathbf B},
are electromagnetic energy density , electric and magnetic fields respectively.
The electromagnetic pressure {P}={W} may be sufficiently high to explode capacity.
Thus electric and magnetic fields do carry momentum.
Light (visible, UV, radio) is an electromagnetic wave and also has momentum. Even though photons (the particle aspect of light) have no mass, they still carry momentum. This leads to applications such as the solar sail.
Momentum is conserved in an electrodynamic system (it may change from momentum in the fields to mechanical momentum of moving parts). The treatment of the momentum of a field is usually accomplished by considering the so-called energy-momentum tensor and the change in time of the Poynting vector integrated over some volume. This is a tensor field which has components related to the energy density and the momentum density.
The definition canonical momentum corresponding to the momentum operator of quantum mechanics when it interacts with the electromagnetic field is, using the principle of least coupling:
instead of the customary
where: | Momentum
Template:Otheruses1
Template:Classical mechanics
In classical mechanics, momentum (pl. momenta; SI unit kg·m/s, or, equivalently, N·s) is the product of the mass and velocity of an object (p=mv). For more accurate measures of momentum, see the section "modern definitions of momentum" on this page. It is sometimes referred to as linear momentum to distinguish it from the related subject of angular momentum. Linear momentum is a vector quantity, since it has a direction as well as a magnitude. Angular momentum is a pseudovector quantity because it gains an additional sign flip under an improper rotation. The total momentum of any group of objects remains the same unless outside forces act on the objects.
Momentum is a conserved quantity, meaning that the total momentum of any closed system (one not affected by external forces) cannot change.
# History of the concept
The word for the general concept of mōmentum was used in the Roman Republic primarily to mean "a movement, motion (as an indwelling force ...)." A fish was able to change velocity (velocitas) through the mōmentum of its tail.[1] The word is formed by an accretion of suffices on the stem of Latin movēre, "to move." A movi-men- is the result of the movēre just as frag-men- is the result of frangere, "to break." Extension by -to- obtains mōvimentum and fragmentum, the former contracting to mōmentum.[2]
The mōmentum was not merely the motion, which was mōtus, but was the power residing in a moving object, captured by today's mathematical definitions. A mōtus, "movement", was a stage in any sort of change,[3] while velocitas, "swiftness", captured only speed. The Romans, due to limitations inherent in the Roman numeral system,Template:Clarifyme were unable to go further with the perception.[citation needed]
The concept of momentum in classical mechanics was originated by a number of great thinkers and experimentalists. The first of these was Ibn Sina (Avicenna) circa 1000, who referred to impetus as proportional to weight times velocity.[4] René Descartes later referred to mass times velocity as the fundamental force of motion. Galileo in his Two New Sciences used the Italian word "impeto."
The question has been much debated as to what Sir Isaac Newton's contribution to the concept was. Apparently nothing, except to state more fully and with better mathematics what was already known. The first and second of Newton's Laws of Motion had already been stated by John Wallis in his 1670 work, Mechanica slive De Motu, Tractatus Geometricus: "the initial state of the body, either of rest or of motion, will persist" and "If the force is greater than the resistance, motion will result...."[5] Wallis uses momentum and vis for force.
Newton's "Mathematical Principles of Natural History" when it first came out in 1686 showed a similar casting around for words to use for the mathematical momentum. His Definition II[6] defines quantitas motus, "quantity of motion," as "arising from the velocity and quantity of matter conjointly", which identifies it as momentum.[7] Thus when in Law II he refers to mutatio motus, "change of motion," being proportional to the force impressed, he is generally taken to mean momentum and not motion.[8]
It remained only to assign a standard term to the quantity of motion. The first use of "momentum" in its proper mathematical sense is not clear but by the time of Jenning's Miscellanea in 1721, four years before the final edition of Newton's Principia Mathematica, momentum M or "quantity of motion" was being defined for students as "a rectangle", the product of Q and V where Q is "quantity of material" and V is "velocity", s/t.[9]
# Linear momentum of a particle
If an object is moving in any reference frame, then it has momentum in that frame. It is important to note that momentum is frame dependent. That is, the same object may have a certain momentum in one frame of reference, but a different amount in another frame. For example, a moving object has momentum in a reference frame fixed to a spot on the ground, while at the same time having 0 momentum in a reference frame attached to the object's center of mass.
The amount of momentum that an object has depends on two physical quantities: the mass and the velocity of the moving object in the frame of reference. In physics, the usual symbol for momentum is a small bold p (bold because it is a vector); so this can be written:
where:
Example: a model airplane of 1 kg travelling due north at 1 m/s in straight and level flight has a momentum of 1 kg m/s due north measured from the ground. To the dummy pilot in the cockpit it has a velocity and momentum of zero.
According to Newton's second law the rate of change of the momentum of a particle is proportional to the resultant force acting on the particle and is in the direction of that force. In the case of constant mass, and velocities much less than the speed of light, this definition results in the equation
or just simply
where F is understood to be the resultant.
Example: a model airplane of 1 kg accelerates from rest to a velocity of 1 m/s due north in 1 sec. The thrust required to produce this acceleration is 1 newton. The change in momentum is 1 kg-m/sec. To the dummy pilot in the cockpit there is no change of momentum. Its pressing backward in the seat is a reaction to the unbalanced thrust, shortly to be balanced by the drag.
# Linear momentum of a system of particles
## Relating to mass and velocity
The linear momentum of a system of particles is the vector sum of the momenta of all the individual objects in the system.
where
It can be shown that, in the center of mass frame the momentum of a system is zero. Additionally, the momentum in a frame of reference that is moving at a velocity vcm with respect to that frame is simply:
where:
## Relating to force- General equations of motion
The linear momentum of a system of particles can also be defined as the product of the total mass <math>\ M</math> of the system times the velocity of the center of mass <math>\mathbf{v}_{cm}</math>
This is commonly known as Newton's second law.
For a more general derivation using tensors, we consider a moving body (see Figure), assumed as a continuum, occupying a volume <math>\ V</math> at a time <math>\ t</math>, having a surface area <math>\ S</math>, with defined traction or surface forces <math>\ T_i^{(n)}</math> acting on every point of the body surface, body forces <math>\ F_i</math> per unit of volume on every point within the volume <math>\ V</math>, and a velocity field <math>\ v_i</math> prescribed throughout the body. Following the previous equation, The linear momentum of the system is:
By definition the stress vector is <math>\ T_i^{(n)} =\sigma_{ij}n_j</math>, then
Using the Gauss's divergency theorem to convert a surface integral to a volume integral gives
For an arbitrary volume the integrand vanishes, and we have the Cauchy's equations of motion
If a system is in equilibrium, the change in momentum with respect to time is equal to 0, as there is no acceleration.
or using tensors,
These are the equilibrium equations which are used in solid mechanics for solving problems of linear elasticity.
In engineering notation, the equilibrium equations are expressed as
# Conservation of linear momentum
The law of conservation of linear momentum is a fundamental law of nature, and it states that the total momentum of a closed system of objects (which has no interactions with external agents) is constant. One of the consequences of this is that the center of mass of any system of objects will always continue with the same velocity unless acted on by a force from outside the system.
Conservation of momentum is a mathematical consequence of the homogeneity (shift symmetry) of space (position in space is the canonical conjugate quantity to momentum). So, momentum conservation can be philosophically stated as "nothing depends on location per se".
In an isolated system (one where external forces are absent) the total momentum will be constant: this is implied by Newton's first law of motion. Newton's third law of motion, the law of reciprocal actions, which dictates that the forces acting between systems are equal in magnitude, but opposite in sign, is due to the conservation of momentum.
Since position in space is a vector quantity, momentum (being the canonical conjugate of position) is a vector quantity as well - it has direction. Thus, when a gun is fired, the final total momentum of the system (the gun and the bullet) is the vector sum of the momenta of these two objects. Assuming that the gun and bullet were at rest prior to firing (meaning the initial momentum of the system was zero), the final total momentum must also equal 0.
In an isolated system with only two objects, the change in momentum of one object must be equal and opposite to the change in momentum of the other object. Mathematically,
<math>\Delta \mathbf{p}_1 = -\Delta \mathbf{p}_2</math>
Momentum has the special property that, in a closed system, it is always conserved, even in collisions and separations caused by explosive forces. Kinetic energy, on the other hand, is not conserved in collisions if they are inelastic. Since momentum is conserved it can be used to calculate an unknown velocity following a collision or a separation if all the other masses and velocities are known.
A common problem in physics that requires the use of this fact is the collision of two particles. Since momentum is always conserved, the sum of the momenta before the collision must equal the sum of the momenta after the collision:
where:
Usually, we either only know the velocities before or after a collision and would like to also find out the opposite. Correctly solving this problem means you have to know what kind of collision took place. There are two basic kinds of collisions, both of which conserve momentum:
- Elastic collisions conserve kinetic energy as well as total momentum before and after collision.
- Inelastic collisions don't conserve kinetic energy, but total momentum before and after collision is conserved.
### Elastic collisions
A collision between two Pool balls is a good example of an almost totally elastic collision. In addition to momentum being conserved when the two balls collide, the sum of kinetic energy before a collision must equal the sum of kinetic energy after:
Since the 1/2 factor is common to all the terms, it can be taken out right away.
In the case of two objects colliding head on we find that the final velocity
which can then easily be rearranged to
Special Case: m1>>m2
Now consider the case when the mass of one body, say m1, is far greater than that of the other, m2 (m1>>m2).
In that case m1+m2 is approximately equal to m1 and m1-m2 is approximately equal to m1.
Using these approximations, the above formula for <math>v_{2,\mathrm{f}}</math> reduces to <math>v_{2,\mathrm{f}}=2v_{1,\mathrm{i}}-v_{2,\mathrm{i}}</math>.
Its physical interpretation is that in the case of a collision between two bodies, one of which is much more massive than the other, the lighter body ends up moving in the opposite direction with twice the original speed of the more massive body.
Special Case: m1=m2
Another special case is when the collision is between two bodies of equal mass.
Say body m1 moving at velocity v1 strikes body m2 that is at rest (v2).
Putting this case in the equation derived above we will see that after the collision, the body that was moving (m1) will start moving with velocity v2 and the mass m2 will start moving with velocity v1. So there will be an exchange of velocities.
Now suppose one of the masses, say m2, was at rest. In that case after the collision the moving body, m1, will come to rest and the body that was at rest, m2, will start moving with the velocity that m1 had before the collision.
Note that all of these observations are for an elastic collision.
This phenomenon is demonstrated by Newton's cradle, one of the best known examples of conservation of momentum, a real life example of this special case.
In the case of objects colliding in more than one dimension, as in oblique collisions, the velocity is resolved into orthogonal components with one component perpendicular to the plane of collision and the other component or components in the plane of collision. The velocity components in the plane of collision remain unchanged, while the velocity perpendicular to the plane of collision is calculated in the same way as the one-dimensional case.
For example, in a two-dimensional collision, the momenta can be resolved into x and y components. We can then calculate each component separately, and combine them to produce a vector result. The magnitude of this vector is the final momentum of the isolated system.
See the elastic collision page for more details.
<math>x=2a</math>
### Inelastic collisions
A common example of a perfectly inelastic collision is when two snowballs collide and then stick together afterwards. This equation describes the conservation of momentum:
It can be shown that a perfectly inelastic collision is one in which the maximum amount of kinetic energy is converted into other forms. For instance, if both objects stick together after the collision and move with a final common velocity, one can always find a reference frame in which the objects are brought to rest by the collision and 100% of the kinetic energy is converted. This is true even in the relativistic case and utilized in particle accelerators to efficiently convert kinetic energy into new forms of mass-energy (i.e. to create massive particles).
In case of Inelastic collision, there is a parameter attached called coefficient of restitution (denoted by small 'e' or 'c' in many text books). It is defined as the ratio of relative velocity of separation to relative velocity of approach. It is a ratio hence it is a dimensionless quantity.
When we have an elastic collision the value of e (= coefficient of restitution) is 1, i.e. the relative velocity of approach is same as the relative velocity of separation of the colliding bodies. In an elastic collision the Kinetic energy of the system is conserved.
When a collision is not elastic (e<1) it is an inelastic collision. In case of a perfectly inelastic collision the relative velocity of separation of the centre of masses of the colliding bodies is 0. Hence after collision the bodies stick together after collision. In case of an inelastic collision the loss of Kinetic energy is maximum as stated above.
In all types of collision if no external force is acting on the system of colliding bodies, the momentum will always get preserved.
### Explosions
An explosion occurs when an object is divided into two or more fragments due to a release of energy.
Note that kinetic energy in a system of explosion is not conserved because it involves energy transformation. (i.e. kinetic energy changes into heat and sound energy)
http://www.glenbrook.k12.il.us/gbssci/phys/Class/momentum/u4l2e.html
In the exploding cannon demonstration, total system momentum is conserved. The system consists of two objects - a cannon and a tennis ball. Before the explosion, the total momentum of the system is zero since the cannon and the tennis ball located inside of it are both at rest. After the explosion, the total momentum of the system must still be zero. If the ball acquires 50 units of forward momentum, then the cannon acquires 50 units of backwards momentum. The vector sum of the individual momenta of the two objects is 0. Total system momentum is conserved.
See the inelastic collision page for more details.
# Modern definitions of momentum
## Momentum in relativistic mechanics
In relativistic mechanics, in order to be conserved, momentum must be defined as:
where
Relativistic momentum can also be written as invariant mass times the object's proper velocity, defined as the rate of change of object position in the observer frame with respect to time elapsed on object clocks (i.e. object proper time). Relativistic momentum becomes Newtonian momentum: <math> m\mathbf{v} </math> at low speed <math> \big(\mathbf{v}/c \rightarrow 0 \big)</math>.
Relativistic four-momentum as proposed by Albert Einstein arises from the invariance of four-vectors under Lorentzian translation. The four-momentum is defined as:
where
The "length" of the vector is the mass times the speed of light, which is invariant across all reference frames:
Momentum of massless objects
Objects without a rest mass, such as photons, also carry momentum. The formula is:
where
Generalization of momentum
Momentum is the Noether charge of translational invariance. As such, even fields as well as other things can have momentum, not just particles. However, in curved space-time which is not asymptotically Minkowski, momentum isn't defined at all.
## Momentum in quantum mechanics
In quantum mechanics, momentum is defined as an operator on the wave function. The Heisenberg uncertainty principle defines limits on how accurately the momentum and position of a single observable system can be known at once. In quantum mechanics, position and momentum are conjugate variables.
For a single particle with no electric charge and no spin, the momentum operator can be written in the position basis as
where:
- <math>\nabla</math> is the gradient operator;
- <math>\hbar</math> is the reduced Planck constant;
- <math> i = \sqrt{-1} </math> is the imaginary unit.
This is a commonly encountered form of the momentum operator, though not the most general one.
## Momentum in electromagnetism
Electric and magnetic fields possess momentum regardless of whether they are static or
they change in time. It is a great surprise for freshmen who are introduced
to the well known fact of the pressure <math>{P}</math> of an electrostatic (magnetostatic) field upon a metal sphere,
cylindrical capacity or ferromagnetic bar:
where <math>{ W}</math>,
<math>{\mathbf E}</math>, <math>{\mathbf B}</math>,
are electromagnetic energy density , electric and magnetic fields respectively.
The electromagnetic pressure <math>{P}={W}</math> may be sufficiently high to explode capacity.
Thus electric and magnetic fields do carry momentum.
Light (visible, UV, radio) is an electromagnetic wave and also has momentum. Even though photons (the particle aspect of light) have no mass, they still carry momentum. This leads to applications such as the solar sail.
Momentum is conserved in an electrodynamic system (it may change from momentum in the fields to mechanical momentum of moving parts). The treatment of the momentum of a field is usually accomplished by considering the so-called energy-momentum tensor and the change in time of the Poynting vector integrated over some volume. This is a tensor field which has components related to the energy density and the momentum density.
The definition canonical momentum corresponding to the momentum operator of quantum mechanics when it interacts with the electromagnetic field is, using the principle of least coupling:
instead of the customary
where: | https://www.wikidoc.org/index.php/Conservation_of_momentum | |
5119668fbb5c8b1f409d03bd7d68013aed252ca5 | wikidoc | Polyuria | Polyuria
# Overview
Polyuria is the passage of a large volume of urine in a given period (>= 2.5L/24 hours in adult humans). It often appears with increased thirst (polydipsia). Various causes of polyuria include
# Causes
- Central diabetes inispidus (CDI)
Idiopathic CDI: the most common cause of CDI
Familial CDI
Wolfram syndrome ( DIDOMAD syndrome)
Congenital hypopituitarism
Septo-optic dysplasia
Surgery/trauma
Cancer (lung cancer, leukemia, lymphoma)
Hypoxic encephalopathy
Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis)
Post-supraventricular tachycardia
Anorexia nervosa
- Idiopathic CDI: the most common cause of CDI
- Familial CDI
- Wolfram syndrome ( DIDOMAD syndrome)
- Congenital hypopituitarism
- Septo-optic dysplasia
- Surgery/trauma
- Cancer (lung cancer, leukemia, lymphoma)
- Hypoxic encephalopathy
- Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis)
- Post-supraventricular tachycardia
- Anorexia nervosa
- Nephrogenic diabetes inspidous (NDI)
Hereditary NDI
Lithium
Hypercalcemia
Hypokalemia
Renal disease:
Bilateral urinary tract obstruction
Medullary cystic kidney disease
Amyloidosis
Sjogren's syndrome
Autosomal dominant polycystic kidney disease
Sickle cell disease
Medications:
Cidofovir
Foscarnet
Amphotericin B
Demeclocycline
Ifosfamide
Ofloxacin
Orlistat
Didanosine
V2 receptor antagonists
Gestational diabetes insipidus
Craniopharyngioma surgery
Bardet-biedl syndrome
Bartter syndrome
Cystinosis
- Hereditary NDI
- Lithium
- Hypercalcemia
- Hypokalemia
- Renal disease:
Bilateral urinary tract obstruction
Medullary cystic kidney disease
Amyloidosis
Sjogren's syndrome
Autosomal dominant polycystic kidney disease
Sickle cell disease
- Bilateral urinary tract obstruction
- Medullary cystic kidney disease
- Amyloidosis
- Sjogren's syndrome
- Autosomal dominant polycystic kidney disease
- Sickle cell disease
- Medications:
Cidofovir
Foscarnet
Amphotericin B
Demeclocycline
Ifosfamide
Ofloxacin
Orlistat
Didanosine
V2 receptor antagonists
- Cidofovir
- Foscarnet
- Amphotericin B
- Demeclocycline
- Ifosfamide
- Ofloxacin
- Orlistat
- Didanosine
- V2 receptor antagonists
- Gestational diabetes insipidus
- Craniopharyngioma surgery
- Bardet-biedl syndrome
- Bartter syndrome
- Cystinosis
- Primary Polydipsia
- Osmotic diuresis: Diabetes mellitus
## Causes by Organ System
## Causes in Alphabetical Order
- 3,3-dichlorobenzidine
- Aceruloplasminemia
- Acid-base imbalance
- Acute tubular necrosis
- Adrenal adenoma
- Adrenal cancer
- Adrenal cortex neoplasms
- Adrenal gland hyperfunction
- Adrenal incidentaloma
- Adrenocortical carcinoma
- Aldosteronism
- Alsing syndrome
- Altitude diuresis
- Amelogenesis imperfeca
- Amitraz
- Anorexia nervosa
- Apparent mineralocorticoid excess
- Back tumor
- Bartter syndrome
- BCG vaccine
- Bendrofluazide
- Benign prostatic hyperplasia
- Bladder cancer
- Bladder compression
- Bladder diverticulum
- Boichis syndrome
- Bumetanide
- Caffeine poisoning
- Canagliflozin
- Cardiorespiratory disease
- Cerebral salt-wasting syndrome
- Chemotherapy-induced cystitis
- Chronic glomerulonephritis
- Chronic interstitial nephritis
- Chronic kidney disease
- Chronic renal failure
- Chronic wasting disease
- Combat stress reaction
- Congestive heart failure
- Conivaptan
- Conn-louis carcinoma
- Conn's adenoma
- Conn's syndrome
- Cushing syndrome
- Cushing's syndrome
- Cystinosis
- Cystitis
- Danubian endemic familial nephropathy
- Dapagliflozin
- Dend syndrome
- Diabetes insipidus
- Diabetes mellitus
- Diabetic nephropathy
- Diencephalic syndrome
- Diuretic therapY
- DKA
- Early chronic pyelonephritis
- East syndrome
- Ectopic ACTH syndrome
- Electrolyte abnormality
- Empagliflozin
- Eosinophilic cystitis
- Erdheim-chester syndrome
- Excessive riboflavin
- Excessive vitamin d
- Familial hypopituitarism
- Fanconi syndrome
- Foscarnet sodium
- Froelich's syndrome
- Frusemide
- Generalized anxiety disorder
- Gestational diabetes
- Gitelman syndrome
- Glomerulonephritis
- Gonococcal urethritis
- Goserelin
- Hair-an syndrome
- Heerfordt syndrome
- Hemochromatosis
- Hereditary primary fanconi disease
- Hhns
- Hip cancer
- Hormonal
- Hydrochlorothiazide
- Hyperadrenalism
- Hypercalcemia
- Hypercalcuria
- Hyperglycemia
- Hyperosmolar hyperglycemic nonketotic syndrome
- Hyperosmolarity
- Hyperparathyroidism
- Hyperthyroidism
- Hypervitaminosis a
- Hypervitaminosis d
- Hypokalemia
- Hypokalemic periodic paralysis
- Hypopituitarism
- Hypothalamic dysfunction
- Intermediate cystinosis
- Interstitial cystitis
- Isosorbide
- Juniper tar poisoning
- Juvenile nephronophthisis
- Langerhans cell histiocytosis
- Leukemia
- Lithium
- Machado-joseph disease
- Mannitol
- Medullary cystic kidney disease
- Megalocytic interstitial nephritis
- Membranoproliferative glomerulonephritis
- Migraine
- Multiple endocrine neoplasia
- Nabilone
- Nephrocalcinosis
- Nephrogenic diabetes insipidus
- Nephrolithiasis
- Nephronophthisis
- Nephronophthisis type 1
- Nephropathic cystinosis
- Neurologic damage
- Neurosarcoidosis
- Noctural polyuria syndrome
- Oak poisoning
- Oligomeganephronic renal hypoplasia
- Olivopontocerebellar atrophy type 3
- Osmotic diuresis
- Ovarian cysts
- Overactive bladder
- Panhypopituitarism
- Parathyroid cancer
- Paroxysmal tachycardia
- Pathological water intake
- Pelvic lipomatosis
- Phendimetrazine
- Pheochromocytoma
- Pituitary tumors
- Polycystic kidney disease
- Polydipsia
- Postobstructive uropathy
- Postural orthostatic tachycardia syndrome
- Premenstrual syndrome
- Primary hyperaldosteronism
- Primary tubular proximal acidosis
- Probenecid
- Prostate cancer
- Proximal renal tubular acidosis
- Proximal tubulopathy
- Psychogenic polydipsia
- Pyelonephritis
- Radiation cystitis
- Radiographic contrast media
- Reflux nephropathy
- Reiter’s syndrome
- Renal cell cancer
- Renal failure
- Renal tubular acidosis
- Renal tubular transport disorders
- Resolving hematoma
- Rib tumor
- Sassoon hospital syndrome
- Secondary bone cancer
- Seizures
- Senior-loken syndrome
- Serratia urinary tract infection
- Sicca syndrome
- Sickle-cell anemia
- Silicon dioxide
- Sodium ferrocyanide
- Sorbitol
- Streptococcal group b invasive disease
- Syndrome of inappropriate antidiuretic hormone
- Tiagabine
- Tolvaptan
- Toni-fanconi syndrome type 1
- Urethral cancer
- Urethritis
- Urinary outflow obstruction
- Urinary stones
- Urinary tract infection
- Uterine fibroids
- Uterine leiomyoma
- Vagina cancer
- Wandering spleen
- Wolfram's disease
# Differential Diagnosis of Polyuria
# Pathophysiology
## Central diabetes inspidus (CDI)
- Results from a deficiency in production, and release of functional AVP, hence respond to administration of exogenous AVP.
- CDI can be acquired or hereditary. ADH-producing cells' injury in hypothalamus/pituitary can be idiopathic, or due to trauma or infection.
- Hereditary forms of familial CDI can occur secondary to 66 different mutations of the genes encoding AVP-neurophysin II precursor.
## Nephrogenic diabetes insipidus (NDI)
- It results from an inappropriate renal response to AVP and usually reflects a functional defect in V2R or AQP2 protein.
- Administration of AVP, therefore is not sufficient to rectify the concentration defect. It is more commonly an acquired disease.
- Over 225 different mutations in AVPR2 represent almost 90% of hereditary NDI cases.
## Diabetes mellitus
- Glucose-induced osmotic diuresis is the major etiology of polyuria in patients with hyperglycemia.
## Primary polydipsia
- It is presumed that a central defect in thirst regulation has an important role in pathophysiology of polydipsia.
- In some polydipsia patients for example, the osmotic threshold for thirst is reduced below the threshold for release of AVP.
- AVP is suppressed by fall in plasma osmolality(because of excessive water intake), and causes rapid excretion of the excess water and continued stimulation of thirst.
# Complications
- Polyuria can result in dehydration, hypernatremia and electrolyte abnormalities if the etiology is solute diuresis. | Polyuria
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2] Luke Rusowicz-Orazem, B.S., Roshan Dinparasti Saleh M.D.To view a comprehensive algorithm of common findings of urine composition and urine output, click here
# Overview
Polyuria is the passage of a large volume of urine in a given period (>= 2.5L/24 hours in adult humans). It often appears with increased thirst (polydipsia). Various causes of polyuria include
# Causes
- Central diabetes inispidus (CDI)
Idiopathic CDI: the most common cause of CDI[1][2]
Familial CDI[3]
Wolfram syndrome ( DIDOMAD syndrome)[4]
Congenital hypopituitarism[5]
Septo-optic dysplasia[6]
Surgery/trauma[7]
Cancer (lung cancer, leukemia, lymphoma)[1]
Hypoxic encephalopathy[8]
Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis)[9][10]
Post-supraventricular tachycardia[11][12]
Anorexia nervosa[13]
- Idiopathic CDI: the most common cause of CDI[1][2]
- Familial CDI[3]
- Wolfram syndrome ( DIDOMAD syndrome)[4]
- Congenital hypopituitarism[5]
- Septo-optic dysplasia[6]
- Surgery/trauma[7]
- Cancer (lung cancer, leukemia, lymphoma)[1]
- Hypoxic encephalopathy[8]
- Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis)[9][10]
- Post-supraventricular tachycardia[11][12]
- Anorexia nervosa[13]
- Nephrogenic diabetes inspidous (NDI)
Hereditary NDI[14][15]
Lithium[16]
Hypercalcemia[17][18]
Hypokalemia[19][20]
Renal disease:
Bilateral urinary tract obstruction[21]
Medullary cystic kidney disease[22]
Amyloidosis[23]
Sjogren's syndrome[24]
Autosomal dominant polycystic kidney disease[22]
Sickle cell disease[25]
Medications:
Cidofovir[26]
Foscarnet[27]
Amphotericin B
Demeclocycline
Ifosfamide
Ofloxacin
Orlistat
Didanosine[28]
V2 receptor antagonists[29]
Gestational diabetes insipidus[30][31]
Craniopharyngioma surgery[32]
Bardet-biedl syndrome[33]
Bartter syndrome[34]
Cystinosis[35]
- Hereditary NDI[14][15]
- Lithium[16]
- Hypercalcemia[17][18]
- Hypokalemia[19][20]
- Renal disease:
Bilateral urinary tract obstruction[21]
Medullary cystic kidney disease[22]
Amyloidosis[23]
Sjogren's syndrome[24]
Autosomal dominant polycystic kidney disease[22]
Sickle cell disease[25]
- Bilateral urinary tract obstruction[21]
- Medullary cystic kidney disease[22]
- Amyloidosis[23]
- Sjogren's syndrome[24]
- Autosomal dominant polycystic kidney disease[22]
- Sickle cell disease[25]
- Medications:
Cidofovir[26]
Foscarnet[27]
Amphotericin B
Demeclocycline
Ifosfamide
Ofloxacin
Orlistat
Didanosine[28]
V2 receptor antagonists[29]
- Cidofovir[26]
- Foscarnet[27]
- Amphotericin B
- Demeclocycline
- Ifosfamide
- Ofloxacin
- Orlistat
- Didanosine[28]
- V2 receptor antagonists[29]
- Gestational diabetes insipidus[30][31]
- Craniopharyngioma surgery[32]
- Bardet-biedl syndrome[33]
- Bartter syndrome[34]
- Cystinosis[35]
- Primary Polydipsia
- Osmotic diuresis: Diabetes mellitus
## Causes by Organ System
## Causes in Alphabetical Order
- 3,3-dichlorobenzidine
- Aceruloplasminemia
- Acid-base imbalance
- Acute tubular necrosis
- Adrenal adenoma
- Adrenal cancer
- Adrenal cortex neoplasms
- Adrenal gland hyperfunction
- Adrenal incidentaloma
- Adrenocortical carcinoma
- Aldosteronism
- Alsing syndrome
- Altitude diuresis
- Amelogenesis imperfeca
- Amitraz
- Anorexia nervosa
- Apparent mineralocorticoid excess
- Back tumor
- Bartter syndrome
- BCG vaccine
- Bendrofluazide
- Benign prostatic hyperplasia
- Bladder cancer
- Bladder compression
- Bladder diverticulum
- Boichis syndrome
- Bumetanide
- Caffeine poisoning
- Canagliflozin
- Cardiorespiratory disease
- Cerebral salt-wasting syndrome
- Chemotherapy-induced cystitis
- Chronic glomerulonephritis
- Chronic interstitial nephritis
- Chronic kidney disease
- Chronic renal failure
- Chronic wasting disease
- Combat stress reaction
- Congestive heart failure
- Conivaptan
- Conn-louis carcinoma
- Conn's adenoma
- Conn's syndrome
- Cushing syndrome
- Cushing's syndrome
- Cystinosis
- Cystitis
- Danubian endemic familial nephropathy
- Dapagliflozin
- Dend syndrome
- Diabetes insipidus
- Diabetes mellitus
- Diabetic nephropathy
- Diencephalic syndrome
- Diuretic therapY
- DKA
- Early chronic pyelonephritis
- East syndrome
- Ectopic ACTH syndrome
- Electrolyte abnormality
- Empagliflozin
- Eosinophilic cystitis
- Erdheim-chester syndrome
- Excessive riboflavin
- Excessive vitamin d
- Familial hypopituitarism
- Fanconi syndrome
- Foscarnet sodium
- Froelich's syndrome
- Frusemide
- Generalized anxiety disorder
- Gestational diabetes
- Gitelman syndrome
- Glomerulonephritis
- Gonococcal urethritis
- Goserelin
- Hair-an syndrome
- Heerfordt syndrome
- Hemochromatosis
- Hereditary primary fanconi disease
- Hhns
- Hip cancer
- Hormonal
- Hydrochlorothiazide
- Hyperadrenalism
- Hypercalcemia
- Hypercalcuria
- Hyperglycemia
- Hyperosmolar hyperglycemic nonketotic syndrome
- Hyperosmolarity
- Hyperparathyroidism
- Hyperthyroidism
- Hypervitaminosis a
- Hypervitaminosis d
- Hypokalemia
- Hypokalemic periodic paralysis
- Hypopituitarism
- Hypothalamic dysfunction
- Intermediate cystinosis
- Interstitial cystitis
- Isosorbide
- Juniper tar poisoning
- Juvenile nephronophthisis
- Langerhans cell histiocytosis
- Leukemia
- Lithium
- Machado-joseph disease
- Mannitol
- Medullary cystic kidney disease
- Megalocytic interstitial nephritis
- Membranoproliferative glomerulonephritis
- Migraine
- Multiple endocrine neoplasia
- Nabilone
- Nephrocalcinosis
- Nephrogenic diabetes insipidus
- Nephrolithiasis
- Nephronophthisis
- Nephronophthisis type 1
- Nephropathic cystinosis
- Neurologic damage
- Neurosarcoidosis
- Noctural polyuria syndrome
- Oak poisoning
- Oligomeganephronic renal hypoplasia
- Olivopontocerebellar atrophy type 3
- Osmotic diuresis
- Ovarian cysts
- Overactive bladder
- Panhypopituitarism
- Parathyroid cancer
- Paroxysmal tachycardia
- Pathological water intake
- Pelvic lipomatosis
- Phendimetrazine
- Pheochromocytoma
- Pituitary tumors
- Polycystic kidney disease
- Polydipsia
- Postobstructive uropathy
- Postural orthostatic tachycardia syndrome
- Premenstrual syndrome
- Primary hyperaldosteronism
- Primary tubular proximal acidosis
- Probenecid
- Prostate cancer
- Proximal renal tubular acidosis
- Proximal tubulopathy
- Psychogenic polydipsia
- Pyelonephritis
- Radiation cystitis
- Radiographic contrast media
- Reflux nephropathy
- Reiter’s syndrome
- Renal cell cancer
- Renal failure
- Renal tubular acidosis
- Renal tubular transport disorders
- Resolving hematoma
- Rib tumor
- Sassoon hospital syndrome
- Secondary bone cancer
- Seizures
- Senior-loken syndrome
- Serratia urinary tract infection
- Sicca syndrome
- Sickle-cell anemia
- Silicon dioxide
- Sodium ferrocyanide
- Sorbitol
- Streptococcal group b invasive disease
- Syndrome of inappropriate antidiuretic hormone
- Tiagabine
- Tolvaptan
- Toni-fanconi syndrome type 1
- Urethral cancer
- Urethritis
- Urinary outflow obstruction
- Urinary stones
- Urinary tract infection
- Uterine fibroids
- Uterine leiomyoma
- Vagina cancer
- Wandering spleen
- Wolfram's disease
# Differential Diagnosis of Polyuria
# Pathophysiology
## Central diabetes inspidus (CDI)
- Results from a deficiency in production, and release of functional AVP, hence respond to administration of exogenous AVP.[53][54]
- CDI can be acquired or hereditary. ADH-producing cells' injury in hypothalamus/pituitary can be idiopathic, or due to trauma or infection.
- Hereditary forms of familial CDI can occur secondary to 66 different mutations of the genes encoding AVP-neurophysin II precursor.[55]
## Nephrogenic diabetes insipidus (NDI)
- It results from an inappropriate renal response to AVP and usually reflects a functional defect in V2R or AQP2 protein.[56]
- Administration of AVP, therefore is not sufficient to rectify the concentration defect. It is more commonly an acquired disease.[57]
- Over 225 different mutations in AVPR2 represent almost 90% of hereditary NDI cases.
## Diabetes mellitus
- Glucose-induced osmotic diuresis is the major etiology of polyuria in patients with hyperglycemia.[58]
## Primary polydipsia
- It is presumed that a central defect in thirst regulation has an important role in pathophysiology of polydipsia.
- In some polydipsia patients for example, the osmotic threshold for thirst is reduced below the threshold for release of AVP.[59]
- AVP is suppressed by fall in plasma osmolality(because of excessive water intake), and causes rapid excretion of the excess water and continued stimulation of thirst.[60]
# Complications
- Polyuria can result in dehydration, hypernatremia and electrolyte abnormalities if the etiology is solute diuresis. | https://www.wikidoc.org/index.php/Constant_urination | |
2d20921edca402db2918fee8de0390edf5b4b774 | wikidoc | Contempt | Contempt
Contempt is an intense feeling or attitude of regarding someone or something as inferior, base, or worthless—it is similar to scorn. Contempt is also defined as the state of being despised or dishonored; disgrace, and an open disrespect or willful disobedience of the authority of a court of law or legislative body.
One example of contempt could be seen in the character Ebenezer Scrooge from the Charles Dickens book A Christmas Carol. Scrooge was cold hearted, hating everything about Christmas and looked down upon everyone around him, especially the poor.
Professor Robert C. Solomon places contempt on the same line continuum as resentment and anger. According to him the differences between the three emotions are that:
- Resentment is directed toward a higher status individual
- Anger is directed toward an equal status individual
- Contempt is directed toward a lower status individual
Contempt is most often associated within the confines of the court, in law. However, there are many different forms of contempt including, but not limited to:
- Civil contempt
- Constructive contempt
- Criminal contempt
- Direct contempt
- Indirect contempt
- Contempt within fiction
- Contempt within marriage
# Etymology
The word contempt originated in about 1393, from the Latin word contemptus meaning “scorn.” It is the past participle of contemnere and from com- intens. prefix + temnere “to slight, scorn.” The origin is uncertain. Contemptuous appeared in 1529.
# Causes
Contempt is brought about by a combination of anger and disgust. Contempt is not a primary emotion but rather, according to Robert Plutchik’s circumplex model, contempt is actually a mixture of two of the primary emotions anger and disgust. Plutchik’s model shows that like colors, primary emotions can be expressed at different intensities and can mix with one another to form different emotions.
# Universality
Although contempt may not be a primary emotion as seen in Plutchik’s circumplex model, the argument for whether or not contempt is a ‘basic’ emotion (universally recognized) has been disputed and disagreed on for years. Paul Ekman, a widely recognized psychologist, found six emotions that were universally recognized: anger, disgust, fear, joy, sadness, and surprise. Findings on contempt are less clear, though there is at least some preliminary evidence that this emotion and its expression are universally recognized. Another study by Ekman and Karl G. Heider shows evidence for universality in a study across cultures in which the level of agreement about a contempt expression compared to the other six basic emotions (anger, disgust, fear, happiness, sadness, surprise) was greater than 75% in all samples.
# Characteristics
According to the analysis of Macalester Bell, contempt has four distinguishing features :
- Contempt requires a judgment concerning the status or standing of the object of contempt. In particular, contempt involves the judgment that, because of some moral or personal failing or defect, the contemned person has compromised his or her standing vis-à-vis an interpersonal standard that the contemnor treats as important. This may have not been done deliberately but by a lack of status. This lack of status may cause the contemptuous to classify the object of contempt as utterly worthless, or as not fully meeting a particular interpersonal standard. Therefore, contempt is a response to a perceived failure to meet an interpersonal standard.
- Contempt is also a particular way of regarding or attending to the object of contempt, and this form of regard has an unpleasant effective element. However, contempt may be experienced as a highly visceral emotion similar to disgust, or as cool disregard.
- Contempt has a certain comparative element. David Hume in his studies of contempt suggests that contempt essentially requires apprehending the “bad qualities” of someone “as they really are” while simultaneously making a comparison between this person and ourselves. Because of this reflexive element, contempt also involves what we might term a “positive self-feeling” of the contemptuous.
- A characteristic of contempt is the psychological withdrawal or distance one typically feels regarding the object of one’s contempt. This psychological distancing is an essential way of expressing one’s nonidentification with the object of one’s contempt and it precludes sympathetic identification with the object of contempt.
- Contempt for a person involves a way of negatively and comparatively regarding or attending to someone who has not fully lived up to an interpersonal standard that the person extending contempt thinks is important. This form of regard constitutes a psychological withdrawal from the object of contempt.
## Facial Expressions
Many research experiments have been conducted to decide if contempt is recognizable across cultures and some researchers believe contempt is too closely related to the emotion disgust. Even Darwin (1872) noted that contempt shares with sociomoral disgust several common features and one can be mistaken for the other. Both contempt and disgust can fit into the hostility triad, sharing the disapproval of others, and can also be included in the ‘CAD triad’ as they exhibit the common theme of violation of moral ethics.
It was Ekman and Friesen’s study that gave the first recorded percentages of more than 75% of all their samples distinguishing contempt over the other basic six emotions. Ekman and Friesen found the facial expression that universally signals contempt—a tightening and slight raising of the lip corner, primarily on one side of the face.
And although they were the ones who recognized that facial expression as the expression that signaled contempt, it was actually Darwin who first recognized the facial expression for this emotion. Darwin was even more detailed in his description of the facial expressions that occur when contempt is being portrayed. He describes that the nose may be slightly turned up, which apparently follows from the turning up of the upper lip; or the movement may be abbreviated into a mere wrinkling of the nose.
# Responses
The coping behaviors for contempt are neither labeled as withdrawal or approach (can be either). However, the main response of contempt lies within “publicized expression of low regard for the objects held in contempt” (Miller, C.H., 2008). By this reasoning, a person holding contempt would not have the urge to openly confront the person with whom they are at odds with, nor would they themselves try to remove the object of contempt; rather, one who holds contempt would have the tendency to:
- Hold the view that others should remove the object of contempt, or
- Hold the view that the object of contempt should remove itself
So while one would make their feelings known to others, the person with contempt would not necessarily want to directly deal with the situation at hand. One who is experiencing contempt would exhibit negative affective behaviors that may be labeled as “cold” – this simply meaning that one who is experiencing the emotion of contempt would tend to alienate those responsible.
# Cultural Contexts of Contempt
“Ekman and Friesen (1986) identified a specific facial expression that observers in each of 10 cultures, both Western and non-Western, agreed signaled contempt.” In this study, citizens of West Sumatra, Indonesia, were given photos of American, Japanese, and Indonesian peoples. Their ability to classify some facial expressions as contempt versus the other categorical emotions of anger, disgust, happiness, sadness, fear, or surprise (with the level of agreement equating to 75%) shows that generally, across cultures, contempt is universally understood.
“An expression in which the corner of the lip is tightened and raised slightly on one side of the face (or much more strongly on one side than the other) signaled contempt.” This study showed that contempt, as well as the outward expression of contempt, can be pointed out across Western and Non-Western peoples when contrasted with other primary emotions.
Another study by Ekman, Sorenson, and Friesen, published in 1969, studied “Pan-Cultural Elements in Facial Displays of Emotion.” Their findings suggest “that the pan-cultural element in facial displays of emotion is the association between facial muscular movements and discrete primary emotions, although cultures may still differ in what evokes an emotion, in rules for controlling the display of emotion, and in behavioral consequences.”
Although some cultures differ in terms of how emotions are learned, taught and controlled, Ekman, Sorenson, and Friesen have found that cross culturally, emotions can be recognized similarly.
# In law
Contempt in the courtroom is essentially seen as a form of disturbance that may impede the functionality of the court. The judge may impose fines and or jail time upon any person committing contempt of court. The person is usually let out upon their agreement to fulfill the wishes of the court. However, the judge is allowed to keep them there for up to six months without a trial by jury to officially convict them of contempt.
## Civil contempt
Acts of omission may also fall within the realm of contempt. The judge will make use of warnings in most any situation that may lead to a person being charged with contempt. It is relatively rare that a person is charged for contempt without first receiving at least one warning from the judge.
## Constructive contempt
Constructive contempt, also called consequential contempt is when a person fails to fulfill the will of the court as it applies to outside obligations of the person. In most cases, constructive contempt is considered to be in the realm of civil contempt because of its passive nature.
## Indirect Contempt
Indirect contempt is something that is associated with civil and constructive Contempt and involves a failure to follow court orders.
## Criminal contempt
This includes anything that could be called a disturbance such as repeatedly talking out of turn, bringing forth previously banned evidence, or harassment of any other party in the courtroom.
## Direct contempt
Direct contempt is an unacceptable act in the presence of the judge (in facie curiae), and generally begins with a warning, and may be accompanied by an immediate imposition of punishment.
# In popular culture
In 1964 a French film was released under the title of Contempt. It was based on an novel called “Il disprezzo” (1954) by Alberto Moravia. The film featured parallels to the Odyssey and works of Dante.
# Contempt in Marriage
Carstensen, Gottman, and Levenson (1995) found that “Negative emotional behavior, such as expressed anger, sadness, contempt, and other negative emotions, appears to be the best discriminator between satisfied and dissatisfied marriages”. This is a commonly agreed with idea, that contempt can play a large role in bringing down relationships. This is likely due to its destructive nature similar in some ways to greed or a grudge. Carstensen, Gottman, and Levenson (1995) also discovered that “In terms of speaker behaviors, wives were coded as showing more total emotion, negative emotion, anger, joy, contempt, whining, and sadness.”
This supports the stereotypy that women express more emotion than men both in general and in relationships. It also supports the idea that men are less expressive than women and tend to be more defensive minded in conversations.
In the book Blink: The Power of Thinking Without Thinking author Malcolm Gladwell discusses John Gottman's theories of how to predict which couples will stay married. Gottman's theory states that there are four major emotional reactions that are destructive to a marriage: defensiveness, stonewalling, criticism, and contempt. Among these four, Gottman considers contempt the most important of them all. | Contempt
Contempt is an intense feeling or attitude of regarding someone or something as inferior, base, or worthless—it is similar to scorn. Contempt is also defined as the state of being despised or dishonored; disgrace, and an open disrespect or willful disobedience of the authority of a court of law or legislative body.[1]
One example of contempt could be seen in the character Ebenezer Scrooge from the Charles Dickens book A Christmas Carol. Scrooge was cold hearted, hating everything about Christmas and looked down upon everyone around him, especially the poor.
Professor Robert C. Solomon places contempt on the same line continuum as resentment and anger. According to him the differences between the three emotions are that[2]:
- Resentment is directed toward a higher status individual
- Anger is directed toward an equal status individual
- Contempt is directed toward a lower status individual
Contempt is most often associated within the confines of the court, in law. However, there are many different forms of contempt including, but not limited to:
- Civil contempt
- Constructive contempt
- Criminal contempt
- Direct contempt
- Indirect contempt
- Contempt within fiction
- Contempt within marriage
# Etymology
The word contempt originated in about 1393, from the Latin word contemptus meaning “scorn.” It is the past participle of contemnere and from com- intens. prefix + temnere “to slight, scorn.” The origin is uncertain. Contemptuous appeared in 1529.[3]
# Causes
Contempt is brought about by a combination of anger and disgust.[4] Contempt is not a primary emotion but rather, according to Robert Plutchik’s circumplex model, contempt is actually a mixture of two of the primary emotions anger and disgust. Plutchik’s model shows that like colors, primary emotions can be expressed at different intensities and can mix with one another to form different emotions.[5]
# Universality
Although contempt may not be a primary emotion as seen in Plutchik’s circumplex model, the argument for whether or not contempt is a ‘basic’ emotion (universally recognized) has been disputed and disagreed on for years. Paul Ekman, a widely recognized psychologist, found six emotions that were universally recognized: anger, disgust, fear, joy, sadness, and surprise. Findings on contempt are less clear, though there is at least some preliminary evidence that this emotion and its expression are universally recognized.[6] Another study by Ekman and Karl G. Heider shows evidence for universality in a study across cultures in which the level of agreement about a contempt expression compared to the other six basic emotions (anger, disgust, fear, happiness, sadness, surprise) was greater than 75% in all samples.[7]
# Characteristics
According to the analysis of Macalester Bell, contempt has four distinguishing features[8] :
- Contempt requires a judgment concerning the status or standing of the object of contempt. In particular, contempt involves the judgment that, because of some moral or personal failing or defect, the contemned person has compromised his or her standing vis-à-vis an interpersonal standard that the contemnor treats as important. This may have not been done deliberately but by a lack of status. This lack of status may cause the contemptuous to classify the object of contempt as utterly worthless, or as not fully meeting a particular interpersonal standard. Therefore, contempt is a response to a perceived failure to meet an interpersonal standard.
- Contempt is also a particular way of regarding or attending to the object of contempt, and this form of regard has an unpleasant effective element. However, contempt may be experienced as a highly visceral emotion similar to disgust, or as cool disregard.
- Contempt has a certain comparative element. David Hume in his studies of contempt suggests that contempt essentially requires apprehending the “bad qualities” of someone “as they really are” while simultaneously making a comparison between this person and ourselves. Because of this reflexive element, contempt also involves what we might term a “positive self-feeling” of the contemptuous.
- A characteristic of contempt is the psychological withdrawal or distance one typically feels regarding the object of one’s contempt. This psychological distancing is an essential way of expressing one’s nonidentification with the object of one’s contempt and it precludes sympathetic identification with the object of contempt.
- Contempt for a person involves a way of negatively and comparatively regarding or attending to someone who has not fully lived up to an interpersonal standard that the person extending contempt thinks is important. This form of regard constitutes a psychological withdrawal from the object of contempt.
## Facial Expressions
Many research experiments have been conducted to decide if contempt is recognizable across cultures and some researchers believe contempt is too closely related to the emotion disgust. Even Darwin (1872) noted that contempt shares with sociomoral disgust several common features and one can be mistaken for the other. Both contempt and disgust can fit into the hostility triad, sharing the disapproval of others, and can also be included in the ‘CAD triad’ as they exhibit the common theme of violation of moral ethics.[9]
It was Ekman and Friesen’s study that gave the first recorded percentages of more than 75% of all their samples distinguishing contempt over the other basic six emotions. Ekman and Friesen found the facial expression that universally signals contempt—a tightening and slight raising of the lip corner, primarily on one side of the face.[10]
And although they were the ones who recognized that facial expression as the expression that signaled contempt, it was actually Darwin who first recognized the facial expression for this emotion. Darwin was even more detailed in his description of the facial expressions that occur when contempt is being portrayed. He describes that the nose may be slightly turned up, which apparently follows from the turning up of the upper lip; or the movement may be abbreviated into a mere wrinkling of the nose.[11]
# Responses
The coping behaviors for contempt are neither labeled as withdrawal or approach (can be either). However, the main response of contempt lies within “publicized expression of low regard for the objects held in contempt” (Miller, C.H., 2008). By this reasoning, a person holding contempt would not have the urge to openly confront the person with whom they are at odds with, nor would they themselves try to remove the object of contempt; rather, one who holds contempt would have the tendency to:
- Hold the view that others should remove the object of contempt, or
- Hold the view that the object of contempt should remove itself
So while one would make their feelings known to others, the person with contempt would not necessarily want to directly deal with the situation at hand. One who is experiencing contempt would exhibit negative affective behaviors that may be labeled as “cold” – this simply meaning that one who is experiencing the emotion of contempt would tend to alienate those responsible.[12]
# Cultural Contexts of Contempt
“Ekman and Friesen (1986) identified a specific facial expression that observers in each of 10 cultures, both Western and non-Western, agreed signaled contempt.” In this study, citizens of West Sumatra, Indonesia, were given photos of American, Japanese, and Indonesian peoples. Their ability to classify some facial expressions as contempt versus the other categorical emotions of anger, disgust, happiness, sadness, fear, or surprise (with the level of agreement equating to 75%) shows that generally, across cultures, contempt is universally understood.[13]
“An expression in which the corner of the lip is tightened and raised slightly on one side of the face (or much more strongly on one side than the other) signaled contempt.” This study showed that contempt, as well as the outward expression of contempt, can be pointed out across Western and Non-Western peoples when contrasted with other primary emotions.[14]
Another study by Ekman, Sorenson, and Friesen, published in 1969, studied “Pan-Cultural Elements in Facial Displays of Emotion.” Their findings suggest “that the pan-cultural element in facial displays of emotion is the association between facial muscular movements and discrete primary emotions, although cultures may still differ in what evokes an emotion, in rules for controlling the display of emotion, and in behavioral consequences.”[15]
Although some cultures differ in terms of how emotions are learned, taught and controlled, Ekman, Sorenson, and Friesen have found that cross culturally, emotions can be recognized similarly.[16]
# In law
Contempt in the courtroom is essentially seen as a form of disturbance that may impede the functionality of the court. The judge may impose fines and or jail time upon any person committing contempt of court. The person is usually let out upon their agreement to fulfill the wishes of the court. However, the judge is allowed to keep them there for up to six months without a trial by jury to officially convict them of contempt.[17]
## Civil contempt
Acts of omission may also fall within the realm of contempt. The judge will make use of warnings in most any situation that may lead to a person being charged with contempt. It is relatively rare that a person is charged for contempt without first receiving at least one warning from the judge.[18]
## Constructive contempt
Constructive contempt, also called consequential contempt is when a person fails to fulfill the will of the court as it applies to outside obligations of the person. In most cases, constructive contempt is considered to be in the realm of civil contempt because of its passive nature.
## Indirect Contempt
Indirect contempt is something that is associated with civil and constructive Contempt and involves a failure to follow court orders.
## Criminal contempt
This includes anything that could be called a disturbance such as repeatedly talking out of turn, bringing forth previously banned evidence, or harassment of any other party in the courtroom.[19]
## Direct contempt
Direct contempt is an unacceptable act in the presence of the judge (in facie curiae), and generally begins with a warning, and may be accompanied by an immediate imposition of punishment.
# In popular culture
In 1964 a French film was released under the title of Contempt. It was based on an novel called “Il disprezzo” (1954) by Alberto Moravia. The film featured parallels to the Odyssey and works of Dante.
# Contempt in Marriage
Carstensen, Gottman, and Levenson (1995) found that “Negative emotional behavior, such as expressed anger, sadness, contempt, and other negative emotions, appears to be the best discriminator between satisfied and dissatisfied marriages”. This is a commonly agreed with idea, that contempt can play a large role in bringing down relationships. This is likely due to its destructive nature similar in some ways to greed or a grudge. Carstensen, Gottman, and Levenson (1995) also discovered that “In terms of speaker behaviors, wives were coded as showing more total emotion, negative emotion, anger, joy, contempt, whining, and sadness.”
This supports the stereotypy that women express more emotion than men both in general and in relationships. It also supports the idea that men are less expressive than women and tend to be more defensive minded in conversations.[20]
In the book Blink: The Power of Thinking Without Thinking author Malcolm Gladwell discusses John Gottman's theories of how to predict which couples will stay married. Gottman's theory states that there are four major emotional reactions that are destructive to a marriage: defensiveness, stonewalling, criticism, and contempt. Among these four, Gottman considers contempt the most important of them all.
[21] | https://www.wikidoc.org/index.php/Contempt | |
9905e2e65f595d1d0aa01cbbc53187665cd30264 | wikidoc | Variable | Variable
In computer science and mathematics, a variable (Template:PronEng) (sometimes called an object or identifier in computer science) is a symbolic representation used to denote a quantity or expression. In mathematics, a variable often represents an "unknown" quantity that has the potential to change; in computer science, it represents a place where a quantity can be stored. Variables are often contrasted with constants, which are known and unchanging.
The term has a similar meaning in the physical sciences and engineering: a variable is a quantity whose value may vary over the course of an experiment (including simulations), across samples, or during the operation of a system. Variables are generally distinct from parameters, although what is a variable in one context may be a parameter in another. For more on this distinction, see the article on "parameter".
In applied statistics, a variable is a measurable factor, characteristic, or attribute of an individual or a system—in other words, something that might be expected to vary over time or between individuals. Random variables are an idealization of this in mathematical statistics, where they are defined as measurable functions from a probability space to a measurable space.
# History
\mathit{x} commonly represents an unknown variable. Even though any letter can be used, \mathit{x} is the most common choice. This usage can be traced back to the Arabic word šay' شيء = “thing”, which in translated algebra texts and similar was taken into Old Spanish with the pronunciation “šei”, which was written xei, which was soon habitually abbreviated to \mathit{x}. (The Spanish pronunciation of “x” has changed since.) But some sources say that this \mathit{x} is an abbreviation of Latin causa which was a translation of Arabic شيء. That started the habit of using letters to represent quantities in algebra. In mathematics, an “italicized x” (x\!) is often used to avoid potential confusion with the multiplication symbol. By extension beyond mathematics, “X” has come to represent a generic placeholder variable whose value is unknown or secret, as in project X or mister X.
# General overview
Variables are used in open sentences. For instance, in the formula x + 1 = 5, x is a variable which represents an "unknown" number. Variables are often represented by letters of the Roman alphabet, but are also represented by letters of other alphabets, such as the Greek alphabet, as well as various other symbols. In this sense, variables are used as a "fill-in-the-blank" within many fields (mathematics, linguistics, etc.)
## Variable Naming Conventions
The names of variables used within a discipline often following some naming convention.
In mathematics, very common letters for variables are "x", "y", "n", "a" and "b". "x" and "y" are often used because they correspond to the two axis on a graph, while "a" and "b" are used as the coefficients of x and y in the general form of a linear equation. "n" is often used in statistical analysis, eg, "n" being the number of subjects in a study.
# In mathematics
Variables are useful in mathematics because they allow instructions to be specified in a general way. If one were forced to use actual values, then the instructions would only apply in a more narrow set of situations. For example:
- double(1) = 1 + 1 = 2
- double(3) = 3 + 3 = 6
- double(55) = 55 + 55 = 110
- etc.
In the above example, the variable x is a "placeholder" for any number. One important thing we are assuming is that the value of each occurrence of x is the same—that x does not get a new value between the first x and the second x.
(Note that in computer programming languages without referential transparency, changes such as this can occur. Variables in computer programming are also useful for this reason. The term "variable", as used by programmers, is different from the meaning of "variable" as used by mathematicians.)
## In applied statistics
In statistics, variables refer to measurable attributes, as these typically vary over time or between individuals. Variables can be discrete (taking values from a finite or countable set), continuous (having a continuous distribution function), or neither. This is referred to as the level of measurement. Temperature is a continuous variable, while the number of legs of an animal is a discrete variable. This concept of a variable is widely used in the natural, medical and social sciences.
In causal models, a distinction is made between "independent variables" and "dependent variables", the latter being expected to vary in value in response to changes in the former. In other words, an independent variable is presumed to potentially affect a dependent one. In experiments, independent variables include factors that can be altered or chosen by the researcher independent of other factors.
For example, in an experiment to test whether or not the boiling point of water changes with altitude, the altitude is under direct control and is the independent variable, and the boiling point is presumed to depend upon it and is therefore the dependent variable. The collection of results from an experiment, or information to be used to draw conclusions, is known as data. It is often important to consider which variables to allow for, or to directly control or eliminate, in the design of experiments.
There are also quasi-independent variables, which are those variables that are used by researcher as a grouping mechanism, without manipulating the variable. An example of this would be separating people into groups by their gender. Gender cannot be manipulated, but it is used as a way to group. Another example would be separating people on the amount of coffee they drank before beginning an experiment. The researcher cannot change the past, but can use it to differentiate the groups.
While independent variables can refer to quantities and qualities that are under experimental control, they can also include extraneous factors that influence results in a confusing or undesired manner.
In general, if strongly confounding variables exist that can substantially affect the result, then this makes it more difficult to interpret the results. For example, a study into the incidence of cancer with age will also have to take into account variables such as income (poorer people may have less healthy lives), location (some cancers vary depending on diet and sunlight), stress and lifestyle issues (cancer may be related to these more than age), and so on. Failure to at least consider these factors can lead to grossly inaccurate deductions. For this reason, controlling unwanted variables is important in research.
# In computer programming
Variables in computer programming are very different from variables in mathematics and the apparent similarity is source of much confusion. Variables in most of mathematics (those that are extensional and referentially transparent) are time-independent unknowns, while in programming a variable can associate with different values at different times (as they are intensional).
In computer programming a variable is a special value (also often called a reference) that has the property of being able to be associated with another value (or not). What is variable across time is the association. Obtaining the value associated with a variable is often called dereferencing, and creating or changing the association is called assignment.
Variables are usually named by an identifier, but they can be anonymous, and variables can be associated with other variables.
In the computing context, variable identifiers often consist of alphanumeric strings. These identifiers are then used to refer to values in computer memory. This convention of matching identifiers to values is but one of several alternative programmatic conventions for accessing values in computer memory (see also: reflection (computer science)).
## Variable naming conventions
In some programming languages, specific characters (known as sigils) are prefixed or appended to variable identifiers to indicate the variable's type. For example:
- in BASIC, the suffix $ on a variable name indicates that its value is a string;
- in Perl, the sigils $, @, %, and & indicate scalar, array, hash, and subroutine variables, respectively.
- in spreadsheets variables can refer to cells (e.g. $A$2), named ranges, or values in associated source code or functions.
## Variables in source code
In computer source code, a variable name is one way to bind a variable to a memory location; the corresponding value is stored as a data object in that location so that the object can be accessed and manipulated later via the variable's name.
## Variables in spreadsheets
In a spreadsheet, a cell may contain a formula with references to other cells. Such a cell reference is a kind of variable; its value is the value of the referenced cell (see also: reference (computer science)).
## Scope and extent
The scope of a variable describes where in a program's text, the variable may be used, while the extent (or lifetime) describes when in a program's execution a variable has a value. The scope of a variable is actually a property of the name of the variable, and the extent is a property of the variable itself.
A variable name's scope affects its extent.
Scope is a lexical aspect of a variable. Most languages define a specific scope for each variable (as well as any other named entity), which may differ within a given program. The scope of a variable is the portion of the program code for which the variable's name has meaning and for which the variable is said to be "visible". Entrance into that scope typically begins a variable's lifetime and exit from that scope typically ends its lifetime. For instance, a variable with "lexical scope" is meaningful only within a certain block of statements or subroutine. A "global variable", or one with indefinite scope, may be referred to anywhere in the program. It is erroneous to refer to a variable where it is out of scope. Lexical analysis of a program can determine whether variables are used out of scope. In compiled languages, such analysis can be performed statically at compile time.
Extent, on the other hand, is a runtime (dynamic) aspect of a variable. Each binding of a variable to a value can have its own extent at runtime. The extent of the binding is the portion of the program's execution time during which the variable continues to refer to the same value or memory location. A running program may enter and leave a given extent many times, as in the case of a closure.
In portions of code, a variable in scope may never have been given a value, or its value may have been destroyed. Such variables are described as "out of extent" or "unbound". In many languages, it is an error to try to use the value of a variable when it is out of extent. In other languages, doing so may yield unpredictable results. Such a variable may, however, be assigned a new value, which gives it a new extent. By contrast, it is permissible for a variable binding to extend beyond its scope, as occurs in Lisp closures and C static variables. When execution passes back into the variable's scope, the variable may once again be used.
For space efficiency, a memory space needed for a variable may be allocated only when the variable is first used and freed when it is no longer needed. A variable is only needed when it is in scope, but beginning each variable's lifetime when it enters scope may give space to unused variables. To avoid wasting such space, compilers often warn programmers if a variable is declared but not used.
It is considered good programming practice to make the scope of variables as narrow as feasible so that different parts of a program do not accidentally interact with each other by modifying each other's variables. Doing so also prevents action at a distance. Common techniques for doing so are to have different sections of a program use different namespaces, or to make individual variables "private" through either dynamic variable scoping or lexical variable scoping.
Many programming languages employ a reserved value (often named null or nil) to indicate an invalid or uninitialized variable.
## Typed and untyped variables
In statically-typed languages such as Java or ML, a variable also has a type, meaning that only values of a given class (or set of classes) can be stored in it. A variable of a primitive type holds a value of that exact primitive type. A variable of a class type can hold a null reference or a reference to an object whose type is that class type or any subclass of that class type. A variable of an interface type can hold a null reference or a reference to an instance of any class that implements the interface. A variable of an array type can hold a null reference or a reference to an array.
In dynamically-typed languages such as Python, it is values, not variables, which carry type. In Common Lisp, both situations exist simultaneously: a variable is given a type (if undeclared, it is assumed to be T, the universal supertype) which exists at compile time. Values also have types, which can be checked and queried at runtime. See type system.
Typing of variables also allows polymorphisms to be resolved at compile time. However, this is different from the polymorphism used in object-oriented function calls (referred to as virtual functions in C++) which resolves the call based on the value type as opposed to the supertypes the variable is allowed to have.
Variables often store simple data-like integers and literal strings, but some programming languages allow a variable to store values of other datatypes as well. Such languages may also enable functions to be parametric polymorphic. These functions operate like variables to represent data of multiple types. For example, a function named length may determine the length of a list. Such a length function may be parametric polymorphic by including a type variable in its type signature, since the amount of elements in the list is independent of the elements' types.
## Parameters
The formal parameters of functions are also referred to as variables. For instance, in this Python code segment,
and its equivalent code segment in Lisp,
the variable named x is a parameter because it is given a value when the function is called. The integer 5 is the argument which gives x its value. In most languages, function parameters have local scope. This specific variable named x can only be referred to within the addtwo function (though of course other functions can also have variables called x).
## Memory allocation
The specifics of variable allocation and the representation of their values vary widely, both among programming languages and among implementations of a given language. Many language implementations allocate space for local variables, whose extent lasts for a single function call on the call stack, and whose memory is automatically reclaimed when the function returns. (More generally, in name binding, the name of a variable is bound to the address of some particular block (contiguous sequence) of bytes in memory, and operations on the variable manipulate that block. Referencing is more common for variables whose values have large or unknown sizes when the code is compiled. Such variables reference the location of the value instead of the storing value itself, which is allocated from a pool of memory called the heap.
Bound variables have values. A value, however, is an abstraction, an idea; in implementation, a value is represented by some data object, which is stored somewhere in computer memory. The program, or the runtime environment, must set aside memory for each data object and, since memory is finite, ensure that this memory is yielded for reuse when the object is no longer needed to represent some variable's value.
Objects allocated from the heap must be reclaimed specially when the objects are no longer needed. In a garbage-collected language (such as C#, Java, and Lisp), the runtime environment automatically reclaims objects when extant variables can no longer refer to them. In non-garbage-collected languages, such as C, the program (and thus the programmer) must explicitly allocate memory, and then later free it, to reclaim its memory. Failure to do so leads to memory leaks, in which the heap is depleted as the program runs, risking eventual failure from exhausting available memory.
When a variable refers to a data structure created dynamically, some of its components may be only indirectly accessed through the variable. In such circumstances, garbage collectors (or analogous program features in languages that lack garbage collectors) must deal with a case where only a portion of the memory reachable from the variable needs to be reclaimed.
## Constants
A constant is a datum whose value cannot be changed once it is initially bound to a value. In other words, constants cannot be assigned to. In purely functional programming, all data are constant, because there is no assignment.
Although a constant value is specified only once, the constant can be referenced multiple times in a program. Using a constant instead of specifying a value multiple times in the program can not only simplify code maintenance, but it can also supply a meaningful name for it and consolidate such constant assignments to a standard code location (for example, at the beginning).
Programming languages provide one of two kinds of constant variables:
For variables which are references, do not confuse constant references with immutable objects. For example, when a non-constant reference references an immutable object, that reference can be changed so that it references a different object, but the object it originally pointed to cannot be changed (i.e. other references that reference it still see the same information).
Conversely, a constant reference may reference a mutable object. In this case, the reference will always reference the same object (the reference cannot be changed); however, the object that the reference references can still be changed (and other references that also reference that object will see the change), as shown in the following example:
The above code produces the following output:
In languages where a variable can be an object (i.e. C++), such a variable being constant is equivalent to the immutability of that object.
## Variable interpolation
Variable interpolation (also variable substitution, variable expansion) is the process of evaluating an expression or string literal containing one or more variables, yielding a result in which the variables are replaced with their corresponding values in memory. It is a specialized instance of concatenation.
Languages that support variable interpolation include Perl, PHP, Ruby, and most Unix shells. In these languages, variable interpolation only occurs when the string literal is double-quoted, but not when it is single-quoted. The variables are recognized because variables start with a sigil (typically "$") in these languages. Ruby uses the "#" symbol for interpolation, and lets you interpolate any expression, not just variables.
For example, the following Perl code:
$name = "Nancy";
print "$name said Hello World to the crowd of people.";
produces the output: | Variable
In computer science and mathematics, a variable (Template:PronEng) (sometimes called an object or identifier in computer science) is a symbolic representation used to denote a quantity or expression. In mathematics, a variable often represents an "unknown" quantity that has the potential to change; in computer science, it represents a place where a quantity can be stored. Variables are often contrasted with constants, which are known and unchanging.
The term has a similar meaning in the physical sciences and engineering: a variable is a quantity whose value may vary over the course of an experiment (including simulations), across samples, or during the operation of a system. Variables are generally distinct from parameters, although what is a variable in one context may be a parameter in another. For more on this distinction, see the article on "parameter".
In applied statistics, a variable is a measurable factor, characteristic, or attribute of an individual or a system—in other words, something that might be expected to vary over time or between individuals. Random variables are an idealization of this in mathematical statistics, where they are defined as measurable functions from a probability space to a measurable space.
# History
<math>\mathit{x}</math> commonly represents an unknown variable. Even though any letter can be used, <math>\mathit{x}</math> is the most common choice. This usage can be traced back to the Arabic word šay' شيء = “thing”, which in translated algebra texts and similar was taken into Old Spanish with the pronunciation “šei”, which was written xei, which was soon habitually abbreviated to <math>\mathit{x}</math>. (The Spanish pronunciation of “x” has changed since.) But some sources say that this <math>\mathit{x}</math> is an abbreviation of Latin causa which was a translation of Arabic شيء. That started the habit of using letters to represent quantities in algebra. In mathematics, an “italicized x” (<math>x\!</math>) is often used to avoid potential confusion with the multiplication symbol. By extension beyond mathematics, “X” has come to represent a generic placeholder variable whose value is unknown or secret, as in project X or mister X.
# General overview
Variables are used in open sentences. For instance, in the formula x + 1 = 5, x is a variable which represents an "unknown" number. Variables are often represented by letters of the Roman alphabet, but are also represented by letters of other alphabets, such as the Greek alphabet, as well as various other symbols. In this sense, variables are used as a "fill-in-the-blank" within many fields (mathematics, linguistics, etc.)
## Variable Naming Conventions
The names of variables used within a discipline often following some naming convention.
In mathematics, very common letters for variables are "x", "y", "n", "a" and "b". "x" and "y" are often used because they correspond to the two axis on a graph, while "a" and "b" are used as the coefficients of x and y in the general form of a linear equation. "n" is often used in statistical analysis, eg, "n" being the number of subjects in a study.
# In mathematics
Variables are useful in mathematics because they allow instructions to be specified in a general way. If one were forced to use actual values, then the instructions would only apply in a more narrow set of situations. For example:
- double(1) = 1 + 1 = 2
- double(3) = 3 + 3 = 6
- double(55) = 55 + 55 = 110
- etc.
In the above example, the variable x is a "placeholder" for any number. One important thing we are assuming is that the value of each occurrence of x is the same—that x does not get a new value between the first x and the second x.
(Note that in computer programming languages without referential transparency, changes such as this can occur. Variables in computer programming are also useful for this reason. The term "variable", as used by programmers, is different from the meaning of "variable" as used by mathematicians.)
## In applied statistics
In statistics, variables refer to measurable attributes, as these typically vary over time or between individuals. Variables can be discrete (taking values from a finite or countable set), continuous (having a continuous distribution function), or neither. This is referred to as the level of measurement. Temperature is a continuous variable, while the number of legs of an animal is a discrete variable. This concept of a variable is widely used in the natural, medical and social sciences.
In causal models, a distinction is made between "independent variables" and "dependent variables", the latter being expected to vary in value in response to changes in the former. In other words, an independent variable is presumed to potentially affect a dependent one. In experiments, independent variables include factors that can be altered or chosen by the researcher independent of other factors.
For example, in an experiment to test whether or not the boiling point of water changes with altitude, the altitude is under direct control and is the independent variable, and the boiling point is presumed to depend upon it and is therefore the dependent variable. The collection of results from an experiment, or information to be used to draw conclusions, is known as data. It is often important to consider which variables to allow for, or to directly control or eliminate, in the design of experiments.
There are also quasi-independent variables, which are those variables that are used by researcher as a grouping mechanism, without manipulating the variable. An example of this would be separating people into groups by their gender. Gender cannot be manipulated, but it is used as a way to group. Another example would be separating people on the amount of coffee they drank before beginning an experiment. The researcher cannot change the past, but can use it to differentiate the groups.
While independent variables can refer to quantities and qualities that are under experimental control, they can also include extraneous factors that influence results in a confusing or undesired manner.
In general, if strongly confounding variables exist that can substantially affect the result, then this makes it more difficult to interpret the results. For example, a study into the incidence of cancer with age will also have to take into account variables such as income (poorer people may have less healthy lives), location (some cancers vary depending on diet and sunlight), stress and lifestyle issues (cancer may be related to these more than age), and so on. Failure to at least consider these factors can lead to grossly inaccurate deductions. For this reason, controlling unwanted variables is important in research.
# In computer programming
Variables in computer programming are very different from variables in mathematics and the apparent similarity is source of much confusion. Variables in most of mathematics (those that are extensional and referentially transparent) are time-independent unknowns, while in programming a variable can associate with different values at different times (as they are intensional).
In computer programming a variable is a special value (also often called a reference) that has the property of being able to be associated with another value (or not). What is variable across time is the association. Obtaining the value associated with a variable is often called dereferencing, and creating or changing the association is called assignment.
Variables are usually named by an identifier, but they can be anonymous, and variables can be associated with other variables.
In the computing context, variable identifiers often consist of alphanumeric strings. These identifiers are then used to refer to values in computer memory. This convention of matching identifiers to values is but one of several alternative programmatic conventions for accessing values in computer memory (see also: reflection (computer science)).
## Variable naming conventions
In some programming languages, specific characters (known as sigils) are prefixed or appended to variable identifiers to indicate the variable's type. For example:
- in BASIC, the suffix $ on a variable name indicates that its value is a string;
- in Perl, the sigils $, @, %, and & indicate scalar, array, hash, and subroutine variables, respectively.
- in spreadsheets variables can refer to cells (e.g. $A$2), named ranges, or values in associated source code or functions.
## Variables in source code
In computer source code, a variable name is one way to bind a variable to a memory location; the corresponding value is stored as a data object in that location so that the object can be accessed and manipulated later via the variable's name.
## Variables in spreadsheets
In a spreadsheet, a cell may contain a formula with references to other cells. Such a cell reference is a kind of variable; its value is the value of the referenced cell (see also: reference (computer science)).
## Scope and extent
The scope of a variable describes where in a program's text, the variable may be used, while the extent (or lifetime) describes when in a program's execution a variable has a value. The scope of a variable is actually a property of the name of the variable, and the extent is a property of the variable itself.
A variable name's scope affects its extent.
Scope is a lexical aspect of a variable. Most languages define a specific scope for each variable (as well as any other named entity), which may differ within a given program. The scope of a variable is the portion of the program code for which the variable's name has meaning and for which the variable is said to be "visible". Entrance into that scope typically begins a variable's lifetime and exit from that scope typically ends its lifetime. For instance, a variable with "lexical scope" is meaningful only within a certain block of statements or subroutine. A "global variable", or one with indefinite scope, may be referred to anywhere in the program. It is erroneous to refer to a variable where it is out of scope. Lexical analysis of a program can determine whether variables are used out of scope. In compiled languages, such analysis can be performed statically at compile time.
Extent, on the other hand, is a runtime (dynamic) aspect of a variable. Each binding of a variable to a value can have its own extent at runtime. The extent of the binding is the portion of the program's execution time during which the variable continues to refer to the same value or memory location. A running program may enter and leave a given extent many times, as in the case of a closure.
In portions of code, a variable in scope may never have been given a value, or its value may have been destroyed. Such variables are described as "out of extent" or "unbound". In many languages, it is an error to try to use the value of a variable when it is out of extent. In other languages, doing so may yield unpredictable results. Such a variable may, however, be assigned a new value, which gives it a new extent. By contrast, it is permissible for a variable binding to extend beyond its scope, as occurs in Lisp closures and C static variables. When execution passes back into the variable's scope, the variable may once again be used.
For space efficiency, a memory space needed for a variable may be allocated only when the variable is first used and freed when it is no longer needed. A variable is only needed when it is in scope, but beginning each variable's lifetime when it enters scope may give space to unused variables. To avoid wasting such space, compilers often warn programmers if a variable is declared but not used.
It is considered good programming practice to make the scope of variables as narrow as feasible so that different parts of a program do not accidentally interact with each other by modifying each other's variables. Doing so also prevents action at a distance. Common techniques for doing so are to have different sections of a program use different namespaces, or to make individual variables "private" through either dynamic variable scoping or lexical variable scoping.
Many programming languages employ a reserved value (often named null or nil) to indicate an invalid or uninitialized variable.
## Typed and untyped variables
In statically-typed languages such as Java or ML, a variable also has a type, meaning that only values of a given class (or set of classes) can be stored in it. A variable of a primitive type holds a value of that exact primitive type. A variable of a class type can hold a null reference or a reference to an object whose type is that class type or any subclass of that class type. A variable of an interface type can hold a null reference or a reference to an instance of any class that implements the interface. A variable of an array type can hold a null reference or a reference to an array.
In dynamically-typed languages such as Python, it is values, not variables, which carry type. In Common Lisp, both situations exist simultaneously: a variable is given a type (if undeclared, it is assumed to be T, the universal supertype) which exists at compile time. Values also have types, which can be checked and queried at runtime. See type system.
Typing of variables also allows polymorphisms to be resolved at compile time. However, this is different from the polymorphism used in object-oriented function calls (referred to as virtual functions in C++) which resolves the call based on the value type as opposed to the supertypes the variable is allowed to have.
Variables often store simple data-like integers and literal strings, but some programming languages allow a variable to store values of other datatypes as well. Such languages may also enable functions to be parametric polymorphic. These functions operate like variables to represent data of multiple types. For example, a function named length may determine the length of a list. Such a length function may be parametric polymorphic by including a type variable in its type signature, since the amount of elements in the list is independent of the elements' types.
## Parameters
The formal parameters of functions are also referred to as variables. For instance, in this Python code segment,
and its equivalent code segment in Lisp,
the variable named x is a parameter because it is given a value when the function is called. The integer 5 is the argument which gives x its value. In most languages, function parameters have local scope[citation needed]. This specific variable named x can only be referred to within the addtwo function (though of course other functions can also have variables called x).
## Memory allocation
The specifics of variable allocation and the representation of their values vary widely, both among programming languages and among implementations of a given language. Many language implementations allocate space for local variables, whose extent lasts for a single function call on the call stack, and whose memory is automatically reclaimed when the function returns. (More generally, in name binding, the name of a variable is bound to the address of some particular block (contiguous sequence) of bytes in memory, and operations on the variable manipulate that block. Referencing is more common for variables whose values have large or unknown sizes when the code is compiled. Such variables reference the location of the value instead of the storing value itself, which is allocated from a pool of memory called the heap.
Bound variables have values. A value, however, is an abstraction, an idea; in implementation, a value is represented by some data object, which is stored somewhere in computer memory. The program, or the runtime environment, must set aside memory for each data object and, since memory is finite, ensure that this memory is yielded for reuse when the object is no longer needed to represent some variable's value.
Objects allocated from the heap must be reclaimed specially when the objects are no longer needed. In a garbage-collected language (such as C#, Java, and Lisp), the runtime environment automatically reclaims objects when extant variables can no longer refer to them. In non-garbage-collected languages, such as C, the program (and thus the programmer) must explicitly allocate memory, and then later free it, to reclaim its memory. Failure to do so leads to memory leaks, in which the heap is depleted as the program runs, risking eventual failure from exhausting available memory.
When a variable refers to a data structure created dynamically, some of its components may be only indirectly accessed through the variable. In such circumstances, garbage collectors (or analogous program features in languages that lack garbage collectors) must deal with a case where only a portion of the memory reachable from the variable needs to be reclaimed.
## Constants
A constant is a datum whose value cannot be changed once it is initially bound to a value. In other words, constants cannot be assigned to. In purely functional programming, all data are constant, because there is no assignment.
Although a constant value is specified only once, the constant can be referenced multiple times in a program. Using a constant instead of specifying a value multiple times in the program can not only simplify code maintenance, but it can also supply a meaningful name for it and consolidate such constant assignments to a standard code location (for example, at the beginning).
Programming languages provide one of two kinds of constant variables:
For variables which are references, do not confuse constant references with immutable objects. For example, when a non-constant reference references an immutable object, that reference can be changed so that it references a different object, but the object it originally pointed to cannot be changed (i.e. other references that reference it still see the same information).
Conversely, a constant reference may reference a mutable object. In this case, the reference will always reference the same object (the reference cannot be changed); however, the object that the reference references can still be changed (and other references that also reference that object will see the change), as shown in the following example:
The above code produces the following output:
In languages where a variable can be an object (i.e. C++), such a variable being constant is equivalent to the immutability of that object.
## Variable interpolation
Variable interpolation (also variable substitution, variable expansion) is the process of evaluating an expression or string literal containing one or more variables, yielding a result in which the variables are replaced with their corresponding values in memory. It is a specialized instance of concatenation.
Languages that support variable interpolation include Perl, PHP, Ruby, and most Unix shells. In these languages, variable interpolation only occurs when the string literal is double-quoted, but not when it is single-quoted. The variables are recognized because variables start with a sigil (typically "$") in these languages. Ruby uses the "#" symbol for interpolation, and lets you interpolate any expression, not just variables.
For example, the following Perl code:
<source lang="perl">
$name = "Nancy";
print "$name said Hello World to the crowd of people.";
</source>
produces the output: | https://www.wikidoc.org/index.php/Continuous_variable | |
913c402b61bcb54b138930385a36c57b0b3afc32 | wikidoc | Copeptin | Copeptin
Copeptin (also known as CT-proAVP) is a 39-amino acid-long peptide derived from the C-terminus of pre-pro-hormone of arginine vasopressin, neurophysin II and copeptin. Arginine vasopressin (AVP), also known as the antidiuretic hormone (ADH), is involved in multiple cardiovascular and renal pathways and abnormal level of AVP are associated with various diseases. Hence measurement of AVP would useful, but not commonly carried out in clinical practice because of its very short half-life making it difficult to quantify. In contrast, copeptin can be immunologically tested with ease and therefore can be used as a vasopressin surrogate marker.
# Synthesis and secretion
Copeptin is a 39-amino acid-long, glycosylated peptide. It is synthesized mainly in the paraventricular neurons of the hypothalamus and in the supraoptical nucleus. During axonal transport, pre-pro-AVP is proteolytically cleaved into vasopressin, neurophysin II and copeptin. These molecules are then stored in secretory granules in the posterior pituitary and released upon osmotic or non-osmotic (hemodynamical; stress-related) stimuli.
# Function
Once secreted into the bloodstream, there is no known biological role for copeptin. However, when pre-pro-vasopressin is processed during the axonal transport, copeptin may contribute to the 3D folding of vasopressin.
# Blood levels
The concentration of copeptin in the blood circulation ranges from 1 to 12 pmol/L in healthy individuals. The levels of copeptin are slightly higher in men than in women and are not influenced by age. In response to serum osmolality fluctuations, the kinetics of copeptin are comparable to those of vasopressin. For example, patients with an electrolyte disorders such as diabetes insipidus with very low vasopressin concentrations also show very low copeptin concentrations in blood plasma. On the other hand, patients suffering from syndrome of inappropriate antidiuretic hormone secretion show high concentrations of both vasopressin and copeptin.
Fenske found the following normal values for levels in blood change changes during an osmostic load from hypertonic saline infusion:
- Level during euvolemia: 2 and 38 pmol/L". Another view is "Median copeptin levels were significantly higher in the male volunteers compared with the females and levels are modulated by gender (higher in males), eGFR higher when eGFR lower), left atrial size (higher when LA larger), and longer echocardiographic deceleration times (prolonged ventricular filling).
- Slope of change during hypertonic saline infusion: "slope of 0.74 pmol/L and mOsM/kg H2O ... (95% confidence interval , 0.66 to 0.83)"
# Surrogate vasopressin marker
The size and half-life of copeptin permit an easier immunological testing, compared to vasopressin, and hence copeptin is proposed as a reliable AVP surrogate.
The clinical interest in copeptin testing is closely linked to the pathophysiological pathways in which vasopressin is involved: polydipsia-polyuria syndrome, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH) as well as heart failure and acute coronary syndrome.
## Acute myocardial infarction
Several studies have shown that copeptin is released very early during the onset of an acute myocardial infarction (AMI), raising the question of its potential value in the diagnosis of AMI and particularly in ruling-out AMI. Indeed, copeptin is released much earlier than troponin, given that copeptin is actively released from the hypothalamus, while troponin occurs in the bloodstream as a breakdown product from dying cardiomyocytes, making the interpretation of their complementary kinetics a useful tool to rule-out AMI. It has been shown that the combination of a negative result of troponin together with a negative result of copeptin can rule out AMI at emergency department presentation with a negative predictive value ranging from 95% to 100%.
These results have been confirmed in a randomised controlled trial.
## Cardiogenic shock
High concentrations of vasopressin during cardiogenic shock have been widely described. It has been shown that the kinetics of copeptin are similar to vasopressin in that context.
## Heart failure
The prognostic value of vasopressin for prediction of outcome in patients suffering from heart failure has been known since the nineties. Patients presenting with high levels of vasopressin have a worsened outcome. Recently, a similar interest has been demonstrated for copeptin in heart failure. | Copeptin
Copeptin (also known as CT-proAVP) is a 39-amino acid-long peptide derived from the C-terminus of pre-pro-hormone of arginine vasopressin, neurophysin II and copeptin. Arginine vasopressin (AVP), also known as the antidiuretic hormone (ADH), is involved in multiple cardiovascular and renal pathways and abnormal level of AVP are associated with various diseases. Hence measurement of AVP would useful, but not commonly carried out in clinical practice because of its very short half-life making it difficult to quantify. In contrast, copeptin can be immunologically tested with ease and therefore can be used as a vasopressin surrogate marker.
# Synthesis and secretion
Copeptin is a 39-amino acid-long, glycosylated peptide.[1] It is synthesized mainly in the paraventricular neurons of the hypothalamus and in the supraoptical nucleus.[2] During axonal transport, pre-pro-AVP is proteolytically cleaved into vasopressin, neurophysin II and copeptin.[3] These molecules are then stored in secretory granules in the posterior pituitary and released upon osmotic or non-osmotic (hemodynamical; stress-related) stimuli.[2]
# Function
Once secreted into the bloodstream, there is no known biological role for copeptin. However, when pre-pro-vasopressin is processed during the axonal transport, copeptin may contribute to the 3D folding of vasopressin.[2]
# Blood levels
The concentration of copeptin in the blood circulation ranges from 1 to 12 pmol/L in healthy individuals.[4] The levels of copeptin are slightly higher in men than in women[4] and are not influenced by age.[4] In response to serum osmolality fluctuations, the kinetics of copeptin are comparable to those of vasopressin.[4][5] For example, patients with an electrolyte disorders such as diabetes insipidus with very low vasopressin concentrations also show very low copeptin concentrations in blood plasma.[6] On the other hand, patients suffering from syndrome of inappropriate antidiuretic hormone secretion show high concentrations of both vasopressin and copeptin.[7]
Fenske[8] found the following normal values for levels in blood change changes during an osmostic load from hypertonic saline infusion:
- Level during euvolemia: 2 and 38 pmol/L"[8]. Another view is "Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4-44.3) compared with 3.2 (1.0-14.8) pmol/l"[9] and levels are modulated by gender (higher in males), eGFR higher when eGFR lower), left atrial size (higher when LA larger), and longer echocardiographic deceleration times (prolonged ventricular filling)[9].
- Slope of change during hypertonic saline infusion: "slope of 0.74 pmol/L and mOsM/kg H2O ... (95% confidence interval [95% CI], 0.66 to 0.83)"[8]
# Surrogate vasopressin marker
The size and half-life of copeptin permit an easier immunological testing, compared to vasopressin, and hence copeptin is proposed as a reliable AVP surrogate.[10][11]
The clinical interest in copeptin testing is closely linked to the pathophysiological pathways in which vasopressin is involved: polydipsia-polyuria syndrome, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH) as well as heart failure and acute coronary syndrome.[4]
## Acute myocardial infarction
Several studies have shown that copeptin is released very early during the onset of an acute myocardial infarction (AMI),[12][13] raising the question of its potential value in the diagnosis of AMI and particularly in ruling-out AMI.[13][14][15] Indeed, copeptin is released much earlier than troponin, given that copeptin is actively released from the hypothalamus, while troponin occurs in the bloodstream as a breakdown product from dying cardiomyocytes,[16] making the interpretation of their complementary kinetics a useful tool to rule-out AMI.[13][14] It has been shown that the combination of a negative result of troponin together with a negative result of copeptin can rule out AMI at emergency department presentation with a negative predictive value ranging from 95% to 100%.[13][14][15]
These results have been confirmed in a randomised controlled trial.[17][18][19]
## Cardiogenic shock
High concentrations of vasopressin during cardiogenic shock have been widely described.[20][21] It has been shown that the kinetics of copeptin are similar to vasopressin in that context.[22]
## Heart failure
The prognostic value of vasopressin for prediction of outcome in patients suffering from heart failure has been known since the nineties. Patients presenting with high levels of vasopressin have a worsened outcome.[23][24] Recently, a similar interest has been demonstrated for copeptin in heart failure.[12][25][26][27] | https://www.wikidoc.org/index.php/Copeptin | |
074176fed59331fc3b392be94f94657f3022fc65 | wikidoc | Cordlife | Cordlife
CordLife Ltd. is a cord blood banking group based in Singapore and listed on the Australian Stock Exchange. It currently has three cord blood processing and storage facilities, in Singapore, Hong Kong, Jakarta, Indonesia and in Sydney, Australia.
The company was founded in May 2001 as one of the first private cord blood banks in Southeast Asia and the first in Singapore. In December 2002, the company assisted in the first cord blood transplant from a privately banked source in Singapore. In April 2003, the company acquired the Massachusetts-based company, Cytomatrix LLC. In June 2004, the company restructured itself as CyGenics Ltd (ASX:CYN) and listed on the Australian Stock Exchange..
The company proceeded to expand its operations in Southeast Asia and in North Asia with the opening of its facility in Hong Kong in March 2005. In September 2005, the Singapore facility was granted AABB Accreditation. It is currently the only private bank to be so accredited in the region.
In November 2005, the company expanded into Australia by acquiring a majority stake in BioCell Pty Ltd. In January 2006, the company established its presence in Kolkata, India. The occasion was graced by the Singapore Senior Minister Goh Chok Tong. In September 2006, the company announced plans to set up another facility in Jakarta, Indonesia. The Jakarta facility was officially opened in September 2007 and the Kolkata facility is expected to be opened by end 2007. The company also intends to open a larger facility in Singapore.
In December 2006, the company was awarded Technology Pioneer 2007 status by the World Economic Forum. In March 2007, the company renamed itself to CordLife Ltd, to better reflect its focus on cord blood banking. | Cordlife
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
CordLife Ltd. is a cord blood banking group based in Singapore and listed on the Australian Stock Exchange. It currently has three cord blood processing and storage facilities, in Singapore, Hong Kong, Jakarta, Indonesia and in Sydney, Australia.
The company was founded in May 2001 as one of the first private cord blood banks in Southeast Asia and the first in Singapore.[1] In December 2002, the company assisted in the first cord blood transplant from a privately banked source in Singapore.[2] In April 2003, the company acquired the Massachusetts-based company, Cytomatrix LLC.[3] In June 2004, the company restructured itself as CyGenics Ltd (ASX:CYN) and listed on the Australian Stock Exchange.[4].
The company proceeded to expand its operations in Southeast Asia and in North Asia with the opening of its facility in Hong Kong in March 2005.[5] In September 2005, the Singapore facility was granted AABB Accreditation. It is currently the only private bank to be so accredited in the region.
In November 2005, the company expanded into Australia by acquiring a majority stake in BioCell Pty Ltd. In January 2006, the company established its presence in Kolkata, India. The occasion was graced by the Singapore Senior Minister Goh Chok Tong. In September 2006, the company announced plans to set up another facility in Jakarta, Indonesia. The Jakarta facility was officially opened in September 2007[6] and the Kolkata facility is expected to be opened by end 2007. The company also intends to open a larger facility in Singapore.
In December 2006, the company was awarded Technology Pioneer 2007 status by the World Economic Forum.[7] In March 2007, the company renamed itself to CordLife Ltd, to better reflect its focus on cord blood banking. | https://www.wikidoc.org/index.php/Cordlife | |
630ea73dd7d574e026f534375a0d5fd82b647806 | wikidoc | Corundum | Corundum
Corundum (from Tamil kurundam குருந்தம் or kuruvindam குருவிந்தம்) is a crystalline form of aluminium oxide and one of the rock-forming minerals. It is naturally clear, but can have different colors when impurities are present. Transparent specimens are used as gems, called ruby if red, while all other colors are called sapphire. A pinkish-orange sapphire is called padparadscha.
Due to corundum's hardness (pure corundum is defined to have 9.0 Mohs), it can scratch almost every other mineral, leaving behind a streak of white on the other mineral. It is commonly used as an abrasive, on everything from sandpaper to large machines used in machining metals, plastics and wood. Some emery is a mix of corundum and other substances, and the mix is less abrasive, with a lower average Mohs hardness near 8.0.
In addition to its hardness, corundum is unusual for its high density of 4.02 g/cm³, which is very high for a transparent mineral composed of the low atomic mass elements aluminium and oxygen.
Corundum occurs as a mineral in mica schist, gneiss, and some marbles in metamorphic terranes. It also occurs in low silica igneous syenite and nepheline syenite intrusives. Other occurrences are as masses adjacent to ultramafic intrusives, associated with lamprophyre dikes and as large crystals in pegmatites. Because of its hardness and resistance to weathering, it commonly occurs as a detrital mineral in stream and beach sands.
Corundum for abrasives is mined in Zimbabwe, Russia, and India. Historically it was mined from deposits associated with dunites in North Carolina and from a nepheline syenite in Craigmont, Ontario. Emery grade corundum is found on the Greek island of Naxos and near Peekskill, New York. Abrasive corundum is synthetically manufactured from bauxite.
# Synthetic corundum
In 1837 Gaudin made the first synthetic rubies by fusing alumina at a high temperature with a little chromium as a pigment. In 1847 Edelman made white sapphire by fusing alumina in boric acid. In 1877 Frenic and Freil made crystal corundum from which small stones could be cut. Frimy and Auguste Verneuil manufactured artificial ruby by fusing BaF2 and Al2O3 with a little Chromium at temperatures above 2000°C. In 1903 Verneuil announced he could produce synthetic rubies on a commercial scale using this flame fusion process.
The Verneuil process allows the production of flawless single-crystal sapphire, rubies and other corundum gems of much larger size than normally found in nature. It is also possible to grow gem-quality synthetic corundum by flux-growth and hydrothermal synthesis. Because of the simplicity of the methods involved in corundum synthesis, large quantities of these crystals have become available on the market causing a significant reduction of price in recent years. Apart from ornamental uses, synthetic corundum is also used to produce mechanical parts (tubes, rods, bearings, and other machined parts), scratch-resistant watch crystals and windows for optical equipment, spacecraft as well as for lasers. | Corundum
Template:Infobox mineral
Corundum (from Tamil kurundam குருந்தம் or kuruvindam குருவிந்தம்) is a crystalline form of aluminium oxide and one of the rock-forming minerals. It is naturally clear, but can have different colors when impurities are present. Transparent specimens are used as gems, called ruby if red, while all other colors are called sapphire. A pinkish-orange sapphire is called padparadscha.
Due to corundum's hardness (pure corundum is defined to have 9.0 Mohs), it can scratch almost every other mineral, leaving behind a streak of white on the other mineral. It is commonly used as an abrasive, on everything from sandpaper to large machines used in machining metals, plastics and wood. Some emery is a mix of corundum and other substances, and the mix is less abrasive, with a lower average Mohs hardness near 8.0.
In addition to its hardness, corundum is unusual for its high density of 4.02 g/cm³, which is very high for a transparent mineral composed of the low atomic mass elements aluminium and oxygen.
Corundum occurs as a mineral in mica schist, gneiss, and some marbles in metamorphic terranes. It also occurs in low silica igneous syenite and nepheline syenite intrusives. Other occurrences are as masses adjacent to ultramafic intrusives, associated with lamprophyre dikes and as large crystals in pegmatites. Because of its hardness and resistance to weathering, it commonly occurs as a detrital mineral in stream and beach sands.
Corundum for abrasives is mined in Zimbabwe, Russia, and India. Historically it was mined from deposits associated with dunites in North Carolina and from a nepheline syenite in Craigmont, Ontario. Emery grade corundum is found on the Greek island of Naxos and near Peekskill, New York. Abrasive corundum is synthetically manufactured from bauxite.
# Synthetic corundum
In 1837 Gaudin made the first synthetic rubies by fusing alumina at a high temperature with a little chromium as a pigment. In 1847 Edelman made white sapphire by fusing alumina in boric acid. In 1877 Frenic and Freil made crystal corundum from which small stones could be cut. Frimy and Auguste Verneuil manufactured artificial ruby by fusing BaF2 and Al2O3 with a little Chromium at temperatures above 2000°C. In 1903 Verneuil announced he could produce synthetic rubies on a commercial scale using this flame fusion process. [1]
The Verneuil process allows the production of flawless single-crystal sapphire, rubies and other corundum gems of much larger size than normally found in nature. It is also possible to grow gem-quality synthetic corundum by flux-growth and hydrothermal synthesis. Because of the simplicity of the methods involved in corundum synthesis, large quantities of these crystals have become available on the market causing a significant reduction of price in recent years. Apart from ornamental uses, synthetic corundum is also used to produce mechanical parts (tubes, rods, bearings, and other machined parts), scratch-resistant watch crystals and windows for optical equipment, spacecraft as well as for lasers. | https://www.wikidoc.org/index.php/Corundum | |
d2efd1d69b869e8a7a89c29dbfa2d7a08cad0f2f | wikidoc | Corvalol | Corvalol
Corvalol is a barbiturate-based heart medication and a mild tranquilizer, popular in Eastern Europe and the former Soviet Union. It is a transparent liquid with a characteristic strong aroma.
A single dose of Corvalol ( 1 ml ) contains:
- Phenobarbital - 16 mg
- Bromisovalum ( derivative of bromine and valeric acid ) - 20 mg
- Peppermint oil - 1.5 mg
as well as inactive ingredients:
- Sodium hydroxide ( to convert poorly soluble phenobarbital into phenobarbital sodium )
- Ethanol and water as solutes
Corvalol is nearly identical in both composition and effects to Valocordin, main difference being that Corvalolis manufactured in Eastern Europe, whereas Valocordin is manufactured in Germany. The word "Valocordin" itself is a registered trademark of the German pharmaceutical company Krewel Meuselbach GmbH.
In Eastern Europe, Corvalol is believed to be safe enough to use in recommended doses without prescription. However, both primary ingredients of Corvalol may be considered controlled substances in other countries. For example, it is illegal to import this drug into United States ( see Health Hazard with Unapproved Imported Drug from Russia ).
Corvalol produced by
Farmak JSC
63 Frunze Str
Kyiev, UKR
The ingredients on the side are as follows:
Ethyl ester of a-isovaleric acid 20 g/L
Methyl Valerate, 55 g/L
Peppermint oil, 1.42 g/L
Hop oil 0.2 g/L
sodium acetate 5.98 g/l
acetic acid, 3 mL/L
ethyl alcohol 713.5 mL/L
water up to 1 L
Slightly different than the above recipe.
Phenobarbutal is not listed there, but is present.
So, it is illegal for travelers to bring a flask or two when they go to Europe. | Corvalol
Corvalol is a barbiturate-based heart medication and a mild tranquilizer, popular in Eastern Europe and the former Soviet Union. It is a transparent liquid with a characteristic strong aroma.
A single dose of Corvalol ( 1 ml ) contains:
- Phenobarbital - 16 mg
- Bromisovalum ( derivative of bromine and valeric acid ) - 20 mg
- Peppermint oil - 1.5 mg
as well as inactive ingredients:
- Sodium hydroxide ( to convert poorly soluble phenobarbital into phenobarbital sodium )
- Ethanol and water as solutes
Corvalol is nearly identical in both composition and effects to Valocordin, main difference being that Corvalolis manufactured in Eastern Europe, whereas Valocordin is manufactured in Germany. The word "Valocordin" itself is a registered trademark of the German pharmaceutical company Krewel Meuselbach GmbH.
In Eastern Europe, Corvalol is believed to be safe enough to use in recommended doses without prescription. However, both primary ingredients of Corvalol may be considered controlled substances in other countries. For example, it is illegal to import this drug into United States ( see Health Hazard with Unapproved Imported Drug from Russia ).
Corvalol produced by
Farmak JSC
63 Frunze Str
Kyiev, UKR
The ingredients on the side are as follows:
Ethyl ester of a-isovaleric acid 20 g/L
Methyl Valerate, 55 g/L
Peppermint oil, 1.42 g/L
Hop oil 0.2 g/L
sodium acetate 5.98 g/l
acetic acid, 3 mL/L
ethyl alcohol 713.5 mL/L
water up to 1 L
Slightly different than the above recipe.
Phenobarbutal is not listed there, but is present.
So, it is illegal for travelers to bring a flask or two when they go to Europe.
Template:Pharma-stub
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Corvalol | |
07d7f1a115dd9ec72409606efb08a4e968fe85ee | wikidoc | Cotinine | Cotinine
Cotinine is a metabolite of nicotine. Cotinine typically remains in the blood between 48 and 96 hours. The level of cotinine in the blood is proportionate to the amount of exposure to tobacco smoke, so it is a valuable indicator of tobacco smoke exposure, including secondary smoke. Women who smoke menthol cigarettes retain cotinine in the blood for a longer period. Race may also play a role, as black people routinely register higher blood cotinine levels than white people. Several variable factors, such as menthol cigarette preference and puff size, suggest that the explanation for this difference may be more complex than gender or race.
Drug tests can detect cotinine in the blood, urine, or saliva.
The word 'cotinine' is an anagram of 'nicotine'.
There is some research being done on the effects of cotinine on memory and cognition. Some studies have suggested that cotinine (as well as nicotine) improves memory and prevents neuron death. For this reason it has been studied for effectiveness in treating schizophrenia, Alzheimer's and Parkinson's diseases. There is research, however, which also suggests that nicotine and cotinine contribute to Alzheimer's disease in other ways which counter and maybe even negate the possible positive effects they might have | Cotinine
Template:Chembox new
Cotinine is a metabolite of nicotine. Cotinine typically remains in the blood between 48 and 96 hours. The level of cotinine in the blood is proportionate to the amount of exposure to tobacco smoke, so it is a valuable indicator of tobacco smoke exposure, including secondary smoke. Women who smoke menthol cigarettes retain cotinine in the blood for a longer period.[1] Race may also play a role, as black people routinely register higher blood cotinine levels than white people.[2] Several variable factors, such as menthol cigarette preference and puff size, suggest that the explanation for this difference may be more complex than gender or race.
Drug tests can detect cotinine in the blood, urine, or saliva.
The word 'cotinine' is an anagram of 'nicotine'.
There is some research being done on the effects of cotinine on memory and cognition. Some studies have suggested that cotinine (as well as nicotine) improves memory and prevents neuron death. For this reason it has been studied for effectiveness in treating schizophrenia, Alzheimer's and Parkinson's diseases[3]. There is research, however, which also suggests that nicotine and cotinine contribute to Alzheimer's disease in other ways which counter and maybe even negate the possible positive effects they might have[4] | https://www.wikidoc.org/index.php/Cotinine | |
c2e5e1ea42023588261db7c8412216416f6ab2c6 | wikidoc | Coumarin | Coumarin
Coumarin is a chemical compound; a toxin found in many plants, notably in high concentration in the tonka bean, woodruff, and bison grass. It has a sweet scent, readily recognised as the scent of newly-mown hay. It has clinical value as the precursor for several anticoagulants, notably warfarin. It is also used as a gain medium in some dye lasers.
The name comes from a French word, coumarou, for the tonka bean.
# Synthesis
The biosynthesis of coumarin in plants is via hydroxylation, glycolysis and cyclization of cinnamic acid. Coumarin can be prepared in a laboratory in a Perkin reaction between salicylaldehyde and acetic anhydride.
The Pechmann condensation provides another synthesis of coumarin and its derivatives.
# Derivatives
Some naturally occurring coumarin derivatives include umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin), herniarin (7-methoxycoumarin), psoralen and imperatorin. Coumarin and its derivatives are all considered phenylpropanoids.
# Coumarin toxicity
Coumarin is often found in tobacco products and artificial vanilla substitutes, though it has been banned as a food additive in numerous countries since the mid-20th century because it is moderately toxic to the liver and kidneys, with an LD50 of 275 mg/kg - low compared to related compounds. Although only somewhat dangerous to humans, coumarin is a potent rodenticide: rats and other rodents largely metabolize it to 3,4-coumarin epoxide, a toxic compound that can cause internal hemorrhage and death. Humans largely metabolize it to 7-hydroxycoumarin, a compound of lower toxicity.
Coumarin was banned as a food additive in the United States in 1978. OSHA considers this compound to be only a lung-specific carcinogen, and "not classifiable as to its carcinogenicity to humans" . Coumarin was banned as an adulterant in cigarettes by tobacco companies in 1997, but due to the lack of reporting requirements to the US Department of Health and Human Services it was still being used as a flavoring additive in pipe tobacco. Coumarin is currently listed by the United States Food and Drug Administration (FDA) among "Substances Generally Prohibited From Direct Addition or Use as Human Food", according to 21 CFR 189.130 , but some natural additives containing coumarin (such as sweet woodruff) are allowed "in alcoholic beverages only" (21 CFR 172.510 ). In Europe, such beverages are very popular, for example Maiwein (white wine with woodruff) and Żubrówka (vodka flavored with bison grass).
European health agencies have warned against consuming high amounts of cassia bark, one of the four species of cinnamon, because of its coumarin content.
Coumarin should be avoided by people with perfume allergy.
Flexitral (Chantilly, VA) has developed an allergen replacement product called Coumane(TM), GRAS. .
# Compounds
Compounds within the coumarin family include:
- brodifacoum,
- bromadiolone,
- coumafuryl, and
- difenacoum.
- Ensaculin
- warfarin
Several of the above compounds are used as rodenticides. | Coumarin
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Coumarin is a chemical compound; a toxin found in many plants, notably in high concentration in the tonka bean, woodruff, and bison grass. It has a sweet scent, readily recognised as the scent of newly-mown hay. It has clinical value as the precursor for several anticoagulants, notably warfarin. It is also used as a gain medium in some dye lasers.
The name comes from a French word, coumarou, for the tonka bean.
# Synthesis
The biosynthesis of coumarin in plants is via hydroxylation, glycolysis and cyclization of cinnamic acid. Coumarin can be prepared in a laboratory in a Perkin reaction between salicylaldehyde and acetic anhydride.
The Pechmann condensation provides another synthesis of coumarin and its derivatives.
# Derivatives
Some naturally occurring coumarin derivatives include umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin), herniarin (7-methoxycoumarin), psoralen and imperatorin. Coumarin and its derivatives are all considered phenylpropanoids.
# Coumarin toxicity
Coumarin is often found in tobacco products and artificial vanilla substitutes, though it has been banned as a food additive in numerous countries since the mid-20th century because it is moderately toxic to the liver and kidneys, with an LD50 of 275 mg/kg - low compared to related compounds. Although only somewhat dangerous to humans, coumarin is a potent rodenticide: rats and other rodents largely metabolize it to 3,4-coumarin epoxide, a toxic compound that can cause internal hemorrhage and death. Humans largely metabolize it to 7-hydroxycoumarin, a compound of lower toxicity.
Coumarin was banned as a food additive in the United States in 1978. OSHA considers this compound to be only a lung-specific carcinogen, and "not classifiable as to its carcinogenicity to humans" [2]. Coumarin was banned as an adulterant in cigarettes by tobacco companies in 1997, but due to the lack of reporting requirements to the US Department of Health and Human Services it was still being used as a flavoring additive in pipe tobacco. Coumarin is currently listed by the United States Food and Drug Administration (FDA) among "Substances Generally Prohibited From Direct Addition or Use as Human Food", according to 21 CFR 189.130 [3][4], but some natural additives containing coumarin (such as sweet woodruff) are allowed "in alcoholic beverages only" (21 CFR 172.510 [5]). In Europe, such beverages are very popular, for example Maiwein (white wine with woodruff) and Żubrówka (vodka flavored with bison grass).
European health agencies have warned against consuming high amounts of cassia bark, one of the four species of cinnamon, because of its coumarin content.[1]
Coumarin should be avoided by people with perfume allergy[2].
Flexitral (Chantilly, VA) has developed an allergen replacement product called Coumane(TM), GRAS. [3].
# Compounds
Compounds within the coumarin family include:
- brodifacoum,[4][5]
- bromadiolone,[6]
- coumafuryl,[7] and
- difenacoum.[8]
- Ensaculin
- warfarin
Several of the above compounds are used as rodenticides. | https://www.wikidoc.org/index.php/Coumarin | |
a38693db90a73c553d8869517826ba2f918f15c5 | wikidoc | Cow dung | Cow dung
# Overview
Cow dung is a term used for the feces of the bovine species. The species includes the cow, buffalo, ox and bullock. Cow dung is basically the digested residue of herbivorous matter which is acted upon by symbiotic bacteria residing within the animal's rumen. The resultant faecal matter is rich in minerals. Colour ranges from greenish to blackish. In due course, the resulting matter turns yellow due to chemical changes caused by sunlight.
# Uses
In many parts of the developing world, cow dung is used as a fertilizer and fuel. Caked and dried cow dung is used as a fuel to cook food in many parts of Asia and Africa. Especially in India where it is known as gobar, cow dung is also used as manure.
In recent times, the dung is collected and used as biogas used to generate electricity and heat. The gas is a rich source of methane and is used in rural areas of India to provide a renewable and stable source of electricity.
Cow dung is also used to line the floor and walls of buildings owing to its insect repellent properties. In cold places, cow dung is used to line the walls of rustic houses as is a cheap thermal insulator. Cow dung has an excellent mosquito repellent property and is used by many companies to produce repellents.
It was also used extensively on Indian Railways to seal smokeboxes on steam locomotives.
Cow dung is also an optional ingredient in the manufacture of adobe mud brick housing depending on the availability of materials at hand.
# Colloquialisms
Cow dung goes by many terms around the world, virtually all of which are colloquial or slang in nature. Cow dung usually appears in a rounded pile and many many of the terms refer to the shape. They include:
- cow pat (used in England; said to originate from the sound made as the faeces drops to the ground)
- cow patty
- cow plop
- pasture patty
- cow chip, (refers to dried cow dung)
- meadow muffin
- cow pie
- country pancake
- buffalo pancake
- landmine | Cow dung
# Overview
Cow dung is a term used for the feces of the bovine species. The species includes the cow, buffalo, ox and bullock. Cow dung is basically the digested residue of herbivorous matter which is acted upon by symbiotic bacteria residing within the animal's rumen. The resultant faecal matter is rich in minerals. Colour ranges from greenish to blackish. In due course, the resulting matter turns yellow due to chemical changes caused by sunlight.
# Uses
In many parts of the developing world, cow dung is used as a fertilizer and fuel. Caked and dried cow dung is used as a fuel to cook food in many parts of Asia and Africa. Especially in India where it is known as gobar, cow dung is also used as manure.
In recent times, the dung is collected and used as biogas used to generate electricity and heat. The gas is a rich source of methane and is used in rural areas of India to provide a renewable and stable source of electricity.
Cow dung is also used to line the floor and walls of buildings owing to its insect repellent properties. In cold places, cow dung is used to line the walls of rustic houses as is a cheap thermal insulator. Cow dung has an excellent mosquito repellent property and is used by many companies to produce repellents.
It was also used extensively on Indian Railways to seal smokeboxes on steam locomotives.
Cow dung is also an optional ingredient in the manufacture of adobe mud brick housing depending on the availability of materials at hand.[1]
# Colloquialisms
Cow dung goes by many terms around the world, virtually all of which are colloquial or slang in nature. Cow dung usually appears in a rounded pile and many many of the terms refer to the shape. They include:
- cow pat (used in England; said to originate from the sound made as the faeces drops to the ground)
- cow patty
- cow plop
- pasture patty
- cow chip, (refers to dried cow dung)
- meadow muffin
- cow pie
- country pancake
- buffalo pancake
- landmine | https://www.wikidoc.org/index.php/Cow_dung | |
274d0933c221c2d979329227b7028de0edfc91ac | wikidoc | Crawling | Crawling
Crawling is a form of animal locomotion generally involving slow movement along the ground, such as that seen in snakes, snails and earthworms. Various mechanisms are involved, for example earthworms move by peristalsis, while snakes undulate their body from side to side. This form of terrestrial locomotion involves much higher levels of friction than running, hopping etc.
# Human crawling
For humans it usually means moving on knees and hands, with support from the toes. Except for using a vehicle or being carried by an animal, it is the main alternative to walking and running. Crawling is used mainly:
- When he/she cannot walk because of being an infant or due to disability or being wounded or sick.
- In very low places (caves, under a table, in a mine, etc.). Sometimes underground miners need to crawl long distances during their work.
- When searching for something on the ground.
- To get down to the ground in gardening
- For stealth (camouflage and quietness)
- To lower the field of vision
- For fun or comical purposes.
- When gun fire or other projectiles are flying over, crawling reduces the risk of being hit.
# Crawling sensation
Crawling, in terms of pain sensations, refers to feeling as if covered with crawling things (i.e., ants). | Crawling
Crawling is a form of animal locomotion generally involving slow movement along the ground, such as that seen in snakes, snails and earthworms. Various mechanisms are involved, for example earthworms move by peristalsis, while snakes undulate their body from side to side.[1] This form of terrestrial locomotion involves much higher levels of friction than running, hopping etc.
# Human crawling
For humans it usually means moving on knees and hands, with support from the toes. Except for using a vehicle or being carried by an animal, it is the main alternative to walking and running. Crawling is used mainly:
- When he/she cannot walk because of being an infant or due to disability or being wounded or sick.
- In very low places (caves, under a table, in a mine, etc.). Sometimes underground miners need to crawl long distances during their work.
- When searching for something on the ground.
- To get down to the ground in gardening
- For stealth (camouflage and quietness)
- To lower the field of vision
- For fun or comical purposes.
- When gun fire or other projectiles are flying over, crawling reduces the risk of being hit.
# Crawling sensation
Crawling, in terms of pain sensations, refers to feeling as if covered with crawling things (i.e., ants). | https://www.wikidoc.org/index.php/Crawling | |
a7a327fbe7000a62694b39e467920869ce317478 | wikidoc | Creatine | Creatine
Creatine is nitrogenous organic acid which naturally occurs in vertebrates and helps to supply energy to muscle and nerve cells. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle which he later named creatine after the Greek word for flesh, Kreas.
# Function
Creatine by way of conversion to and from phosphocreatine is present and functions in all vertebrates, as well as some invertebrates, in conjunction with the enzyme creatine kinase. A similar system based on arginine/phosphoarginine operates in many invertebrates via the action of Arginine Kinase. The presence of this energy buffer system keeps the ATP/ADP ratio high at subcellular places where ATP is needed, which ensures that the free energy of ATP remains high and minimizes the loss of adenosine nucleotides, which would cause cellular dysfunction. Such high-energy phosphate buffers in the form of phosphocreatine or phosphoarginine are known as phosphagens. In addition, due to the presence of subcompartmentalized Creatine Kinase Isoforms at specific sites of the cell, the phosphocreatine/creatine kinase system also acts as an intracellular energy transport system from those places where ATP is generated (mitochondria and glycolysis) to those places where energy is needed and used, e.g. at the myofibrils for muscle contraction, at the sarcoplasmic reticulum (SR) for calcium pumping and many more biological processes which depend on ATP.
# Biosynthesis
In the human body, approximately half of the daily creatine is biosynthesized mainly in the vertebrates by the use of parts from three different amino acids - arginine, glycine, and methionine. The rest is taken in by alimentary sources mainly from fresh fish and meat. 95% of it is later stored in the skeletal muscles, with the rest in the brain, heart, testes, inner ear hair cells and other organs and cells.
The enzyme GAMT (NOTE: image states "GATM" which is incorrect!) (guanidinoacetate N-methyltransferase, also known as L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.
The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas.
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.
# Controversy
Creatine use in sports as a purported performance enhancer is controversial. Though its effectiveness is not proven, many believe creatine should be banned for athletes as a performance enhancing substance, but due to the legal ingredients it still remains a commonly used substance.
# Sources
In humans, approximately half of stored creatine originates from food (mainly from fresh meat and fish). Since vegetables do not contain creatine, vegetarians clearly show lower levels of muscle creatine which rise upon creatine supplementation more than meat-eaters.
# Creatine and the treatment of muscular diseases
Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neurological and neuromuscular diseases (arthritis, congestive heart failure, parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).
Two studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study demonstrated that creatine was twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway which leads to cell death.
Secondly, creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders. | Creatine
Template:Chembox new
Creatine is nitrogenous organic acid which naturally occurs in vertebrates and helps to supply energy to muscle and nerve cells. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle which he later named creatine after the Greek word for flesh, Kreas.
# Function
Creatine by way of conversion to and from phosphocreatine is present and functions in all vertebrates, as well as some invertebrates, in conjunction with the enzyme creatine kinase. A similar system based on arginine/phosphoarginine operates in many invertebrates via the action of Arginine Kinase. The presence of this energy buffer system keeps the ATP/ADP ratio high at subcellular places where ATP is needed, which ensures that the free energy of ATP remains high and minimizes the loss of adenosine nucleotides, which would cause cellular dysfunction. Such high-energy phosphate buffers in the form of phosphocreatine or phosphoarginine are known as phosphagens. In addition, due to the presence of subcompartmentalized Creatine Kinase Isoforms at specific sites of the cell, the phosphocreatine/creatine kinase system also acts as an intracellular energy transport system from those places where ATP is generated (mitochondria and glycolysis) to those places where energy is needed and used, e.g. at the myofibrils for muscle contraction, at the sarcoplasmic reticulum (SR) for calcium pumping and many more biological processes which depend on ATP.
# Biosynthesis
In the human body, approximately half of the daily creatine is biosynthesized mainly in the vertebrates by the use of parts from three different amino acids - arginine, glycine, and methionine. The rest is taken in by alimentary sources mainly from fresh fish and meat. 95% of it is later stored in the skeletal muscles, with the rest in the brain, heart, testes, inner ear hair cells and other organs and cells.
The enzyme GAMT (NOTE: image states "GATM" which is incorrect!) (guanidinoacetate N-methyltransferase, also known as L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas[1].
The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas[2].
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects[3].
# Controversy
Creatine use in sports as a purported performance enhancer is controversial.[citation needed] Though its effectiveness is not proven, many believe creatine should be banned for athletes as a performance enhancing substance, but due to the legal ingredients it still remains a commonly used substance.[citation needed]
# Sources
In humans, approximately half of stored creatine originates from food (mainly from fresh meat and fish). Since vegetables do not contain creatine, vegetarians clearly show lower levels of muscle creatine which rise upon creatine supplementation more than meat-eaters.[1]
# Creatine and the treatment of muscular diseases
Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neurological and neuromuscular diseases (arthritis, congestive heart failure, parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).
Two studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study demonstrated that creatine was twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease)[2]. The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway which leads to cell death.
Secondly, creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders[3]. | https://www.wikidoc.org/index.php/Creatine | |
5a57e3da3446926f983edf6d45e3a6d67dcf1b58 | wikidoc | Creosote | Creosote
Creosote is the name used for a variety of products including wood creosote and coal tar creosote. Wood creosote is created by high temperature treatment of beech and other woods, or from the resin of the Creosote bush.
The term creosote, however, is most commonly used to refer to coal tar creosote. Coal tar creosote is is an EPA-registered wood preservative. It is distilled from crude coke oven tar, and is mainly composed of polycyclic aromatic hydrocarbons (PAHs), but also contains phenols and cresols.
The term is also used to refer to the buildup of carbon materials in chimneys from wood-burning fires.
# Wood creosote
Wood creosote is a colorless to yellowish greasy liquid with a smoky odor and burned taste.
Wood creosote has been used as a disinfectant, a laxative, and a cough treatment, but these have mostly been replaced by newer medicines.
The popular Japanese anti-diarrheic Seirogan has 133 mg creosote (from beech, maple or oak wood) per adult dose as its primary ingredient.
# Coal tar creosote
When most people use the term creosote, they are referring to coal tar creosote. Coal tar creosote is the most widely used wood preservative in the United States. It is a thick, oily liquid typically amber to black in color. The American Wood Preservers' association states that creosote "shall be a distillate derived entirely from tars produced from the carbonization of bituminous coal." Coal tar used for certain applications may be a mixture of coal tar distillate and coal tar. See, AWPA Standards
The prevailing use of creosote in the United States is to preserve wooden utilities/telephone poles, railroad cross ties, switch ties and bridge timbers from decay. It is registered with USEPA for this purpose. Coal tar products are also used in medicines to treat diseases such as psoriasis, and as animal and bird repellents, insecticides, animal dips, and fungicides. Some over the counter anti-dandruff shampoos contain coal tar solutions.
# Chimney creosote and chimney fires
The type of creosote that builds up in the chimney of a wood burning fireplace is distinct from wood creosote and coal tar creosote. Fireplace creosote is actually condensed flue gas, consisting of steam and vaporized but unburned carbon materials present in the wood. Flue gas has fairly high ignition temperature, and most wood stoves utilizing natural air convection do not have a high enough combustion temperature to ignite the vapors. Consequently, flue gas floats up the exhaust pipe, and then condenses onto the cool interior lining of the chimney forming what is often referred to as creosote. Burning a large hot fire helps prevent creosote buildup that could lead to a chimney fire because the continued heat output from the fire eventually warms up the lining of the chimney sufficiently to revaporize the deposited creosote. Chimney fires can be volcanic and have been known to spread to roofs, destroying homes. It is important to remove chimney creosote as it builds up.
# Health effects of coal tar creosote
According to the Agency for Toxic Substances and Disease Registry (ATSDR), eating food or drinking water contaminated with high levels of coal tar creosote may cause a burning in the mouth and throat, and stomach pains.
ATDSR also states that brief direct contact with large amounts of coal tar creosote may result in a rash or severe irritation of the skin, chemical burns of the surfaces of the eyes, convulsions and mental confusion, kidney or liver problems, unconsciousness, and even death. Longer direct skin contact with low levels of creosote mixtures or their vapors can result in increased light sensitivity, damage to the cornea, and skin damage. Longer exposure to creosote vapors can cause irritation of the respiratory tract.
The International Agency for Research on Cancer (IARC) has determined that coal tar creosote is probably carcinogenic to humans, based on adequate animal evidence and limited human evidence. It is instructive to note that the animal testing relied upon by IARC involved the continuous application of creosote to the shaved skin of rodents. After weeks of creosote application, the animals developed cancerous skin lesions and in one test, lesions of the lung. The United States Environmental Protection Agency has stated that coal tar creosote is a possible human carcinogen.
There is no unique exposure pathway of children to creosote. Children exposed to creosote will probably experience the same health effects seen in adults exposed to creosote. It is unknown whether children differ from adults in their susceptibility to health effects from creosote.
A 2005 mortality study of creosote workers found no evidence supporting an increased risk of cancer death as a result of exposure to creosote. Based on the findings of the largest mortality study to date of workers employed in creosote wood treating plants, there is no evidence that employment at creosote wood-treating plants or exposure to creosote-based preservatives was associated with any significant mortality increase from either site-specific cancers or non-malignant diseases. The study consisted of 2,179 employees at eleven plants in the United States where wood was treated with creosote preservatives. Some workers began work in the 1940s to 1950s. The observation period of the study covered 1979- 2001. The average length of employment was 12.5 years. One third of the study subjects was employed for over 15 years. | Creosote
Creosote is the name used for a variety of products including wood creosote and coal tar creosote. Wood creosote is created by high temperature treatment of beech and other woods, or from the resin of the Creosote bush.
The term creosote, however, is most commonly used to refer to coal tar creosote. Coal tar creosote is is an EPA-registered wood preservative. It is distilled from crude coke oven tar, and is mainly composed of polycyclic aromatic hydrocarbons (PAHs), but also contains phenols and cresols.
The term is also used to refer to the buildup of carbon materials in chimneys from wood-burning fires.
# Wood creosote
Wood creosote is a colorless to yellowish greasy liquid with a smoky odor and burned taste.
Wood creosote has been used as a disinfectant, a laxative, and a cough treatment, but these have mostly been replaced by newer medicines.
The popular Japanese anti-diarrheic Seirogan has 133 mg creosote (from beech, maple or oak wood) per adult dose as its primary ingredient. [1]
# Coal tar creosote
When most people use the term creosote, they are referring to coal tar creosote. Coal tar creosote is the most widely used wood preservative in the United States. It is a thick, oily liquid typically amber to black in color. The American Wood Preservers' association states that creosote "shall be a distillate derived entirely from tars produced from the carbonization of bituminous coal." Coal tar used for certain applications may be a mixture of coal tar distillate and coal tar. See, AWPA Standards
The prevailing use of creosote in the United States is to preserve wooden utilities/telephone poles, railroad cross ties, switch ties and bridge timbers from decay. It is registered with USEPA for this purpose. Coal tar products are also used in medicines to treat diseases such as psoriasis, and as animal and bird repellents, insecticides, animal dips, and fungicides. Some over the counter anti-dandruff shampoos contain coal tar solutions.
# Chimney creosote and chimney fires
The type of creosote that builds up in the chimney of a wood burning fireplace is distinct from wood creosote and coal tar creosote. Fireplace creosote is actually condensed flue gas, consisting of steam and vaporized but unburned carbon materials present in the wood. Flue gas has fairly high ignition temperature, and most wood stoves utilizing natural air convection do not have a high enough combustion temperature to ignite the vapors. Consequently, flue gas floats up the exhaust pipe, and then condenses onto the cool interior lining of the chimney forming what is often referred to as creosote. Burning a large hot fire helps prevent creosote buildup that could lead to a chimney fire because the continued heat output from the fire eventually warms up the lining of the chimney sufficiently to revaporize the deposited creosote. Chimney fires can be volcanic and have been known to spread to roofs, destroying homes. It is important to remove chimney creosote as it builds up.
# Health effects of coal tar creosote
According to the Agency for Toxic Substances and Disease Registry (ATSDR), eating food or drinking water contaminated with high levels of coal tar creosote may cause a burning in the mouth and throat, and stomach pains.
ATDSR also states that brief direct contact with large amounts of coal tar creosote may result in a rash or severe irritation of the skin, chemical burns of the surfaces of the eyes, convulsions and mental confusion, kidney or liver problems, unconsciousness, and even death. Longer direct skin contact with low levels of creosote mixtures or their vapors can result in increased light sensitivity, damage to the cornea, and skin damage. Longer exposure to creosote vapors can cause irritation of the respiratory tract.
The International Agency for Research on Cancer (IARC) has determined that coal tar creosote is probably carcinogenic to humans, based on adequate animal evidence and limited human evidence. It is instructive to note that the animal testing relied upon by IARC involved the continuous application of creosote to the shaved skin of rodents. After weeks of creosote application, the animals developed cancerous skin lesions and in one test, lesions of the lung. The United States Environmental Protection Agency has stated that coal tar creosote is a possible human carcinogen.
There is no unique exposure pathway of children to creosote. Children exposed to creosote will probably experience the same health effects seen in adults exposed to creosote. It is unknown whether children differ from adults in their susceptibility to health effects from creosote.
A 2005 mortality study of creosote workers found no evidence supporting an increased risk of cancer death as a result of exposure to creosote. Based on the findings of the largest mortality study to date of workers employed in creosote wood treating plants, there is no evidence that employment at creosote wood-treating plants or exposure to creosote-based preservatives was associated with any significant mortality increase from either site-specific cancers or non-malignant diseases. The study consisted of 2,179 employees at eleven plants in the United States where wood was treated with creosote preservatives. Some workers began work in the 1940s to 1950s. The observation period of the study covered 1979- 2001. The average length of employment was 12.5 years. One third of the study subjects was employed for over 15 years.[1] | https://www.wikidoc.org/index.php/Creosote | |
b7e9339ccdf4cd184f18b7ac01b1053777daff7c | wikidoc | Crepitus | Crepitus
# Overview
Crepitus is a medical term to describe the grating, crackling or popping sounds and sensations experienced under the skin and joints. The sound can be created when two rough surfaces in the human body come into contact - for example, in osteoarthritis when the cartilage around joints has eroded away and the joint ends grind against one another, or when the fracture surfaces of two broken bones rub together.
In soft tissues, crepitus can be produced when gas is introduced into an area where it normally isn't present. The term can also be used when describing the sounds produced by lung conditions such as interstitial lung disease - these are also referred to as "rales". Crepitus is often loud enough to be heard by the human ear, although a stethoscope may be needed to detect instances caused by respiratory diseases.
In times of poor surgical practice, post-surgical complications involved anaerobic infection by Clostridium perfringens strains, which can cause gas gangrene in tissues, also giving rise to crepitus. | Crepitus
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Crepitus is a medical term to describe the grating, crackling or popping sounds and sensations experienced under the skin and joints. The sound can be created when two rough surfaces in the human body come into contact - for example, in osteoarthritis when the cartilage around joints has eroded away and the joint ends grind against one another, or when the fracture surfaces of two broken bones rub together.
In soft tissues, crepitus can be produced when gas is introduced into an area where it normally isn't present. The term can also be used when describing the sounds produced by lung conditions such as interstitial lung disease - these are also referred to as "rales". Crepitus is often loud enough to be heard by the human ear, although a stethoscope may be needed to detect instances caused by respiratory diseases.
In times of poor surgical practice, post-surgical complications involved anaerobic infection by Clostridium perfringens strains, which can cause gas gangrene in tissues, also giving rise to crepitus.
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Crepitus | |
eb7abc55f6230168de73fb44a41aa8e2a6f976d7 | wikidoc | Crucible | Crucible
A crucible is a cup-shaped piece of laboratory equipment used to contain chemical compounds when heating them to very high temperatures. Crucibles are available in several sizes and typically come with a crucible cover (or lid).
# Crucible materials and description
Crucibles and their covers are made of high temperature-resistant materials, usually porcelain or an inert metal. One of the earliest uses of platinum was to make crucibles. More recently, metals such as nickel and zirconium have been used. The lids are typically loose-fitting to allow gases to escape during heating of a sample inside. Crucibles and their lids can come in high form and low form shapes (see Ext. Link 2 below) and in various sizes, but rather small 10–15 ml size porcelain crucibles are commonly used for gravimetric chemical analysis. These small size crucibles and their covers made of porcelain are quite cheap when sold in quantity to laboratories, and the crucibles are sometimes disposed of after use in precise quantitative chemical analysis. There is usually a large mark-up when they are sold individually in hobby shops.
A crucible is also a container in which metals are melted, usually for temperatures above 500 °C. These crucibles are usually made of graphite with clay as a binder. These crucibles are very durable and resist temperatures to over 1600 °C. A crucible is placed into a furnace and, after the melting, the liquid metal is taken out of the furnace and poured into the mold. Some furnaces (usually electric or induction) have an embedded crucible and are tilted when the metal is poured out.
Early crucibles were used by alchemists who attempted to turn base metals into gold.
# Use in chemical analysis
In the area of chemical analysis, crucibles are used in quantitative gravimetric chemical analysis (analysis by measuring mass of an analyte). Common crucible use may be as follows. A residue or precipitate in a chemical analysis method can be collected or filtered from some sample or solution on special "ashless" filter paper. The crucible and lid to be used are pre-weighed very accurately on an analytical balance. After some possible washing and/or pre-drying of this filtrate, the residue on the filter paper can be placed in the crucible and fired (heated at very high temperature) until all the volatiles and moisture are driven out of the sample residue in the crucible. The "ashless" filter paper is completely burned up in this process. The crucible with the sample and lid is allowed to cool in a desiccator. The crucible and lid with the sample inside is weighed very accurately again only after it has completely cooled to room temperature (higher temperature would cause air currents around the balance giving inaccurate results). The mass of the empty, pre-weighed crucible and lid is subtracted from this result to yield the mass of the completely dried residue in the crucible.
A crucible with a bottom perforated with small holes which is designed specifically for use in filtration, especially for gravimetric analysis as just described, is called a Gooch crucible after its inventor, Frank Austen Gooch.
For completely accurate results, the crucible is handled with clean tongs because fingerprints can add weighable mass to the crucible. Porcelain crucibles are hygroscopic, i. e. they absorb a bit of weighable moisture from the air. For this reason, the porcelain crucible and lid is also pre-fired (pre-heating to high temperature) to constant mass before the pre-weighing. This determines the mass of the completely dry crucible and lid. At least two firings, coolings, and weighings resulting in exactly the same mass are needed to confirm constant (completely dry) mass of the crucible and lid and similarly again for the crucible, lid, and sample residue inside. Since the mass of every crucible and lid is different, the pre-firing/pre-weighing must be done for every new crucible/lid used. The desiccator contains desiccant to absorb moisture from the air inside, so the air inside will be completely dry.
## Use in ash content determination
Ash is the completely unburnable inorganic salts in a sample. A crucible can be similarly used to determine the percentage of ash contained in an otherwise burnable sample of material such as coal, wood, or oil. A crucible and its lid are pre-weighed at constant mass as described above. The sample is added to the completely dry crucible and lid and together they are weighed to determine the mass of the sample by difference. The crucible, lid, and sample are then fired to constant mass to completely burn up the sample, leaving behind only the completely unburnable ash. After cooling in dryness, the crucible, lid, and remaining ash are weighed to find the mass of the ash from the sample by difference. | Crucible
A crucible is a cup-shaped piece of laboratory equipment used to contain chemical compounds when heating them to very high temperatures. Crucibles are available in several sizes and typically come with a crucible cover (or lid).
# Crucible materials and description
Crucibles and their covers are made of high temperature-resistant materials, usually porcelain or an inert metal. One of the earliest uses of platinum was to make crucibles. More recently, metals such as nickel and zirconium have been used. The lids are typically loose-fitting to allow gases to escape during heating of a sample inside. Crucibles and their lids can come in high form and low form shapes (see Ext. Link 2 below) and in various sizes, but rather small 10–15 ml size porcelain crucibles are commonly used for gravimetric chemical analysis. These small size crucibles and their covers made of porcelain are quite cheap when sold in quantity to laboratories, and the crucibles are sometimes disposed of after use in precise quantitative chemical analysis. There is usually a large mark-up when they are sold individually in hobby shops.
A crucible is also a container in which metals are melted, usually for temperatures above 500 °C. These crucibles are usually made of graphite with clay as a binder. These crucibles are very durable and resist temperatures to over 1600 °C. A crucible is placed into a furnace and, after the melting, the liquid metal is taken out of the furnace and poured into the mold. Some furnaces (usually electric or induction) have an embedded crucible and are tilted when the metal is poured out.
Early crucibles were used by alchemists who attempted to turn base metals into gold.
# Use in chemical analysis
In the area of chemical analysis, crucibles are used in quantitative gravimetric chemical analysis (analysis by measuring mass of an analyte). Common crucible use may be as follows. A residue or precipitate in a chemical analysis method can be collected or filtered from some sample or solution on special "ashless" filter paper. The crucible and lid to be used are pre-weighed very accurately on an analytical balance. After some possible washing and/or pre-drying of this filtrate, the residue on the filter paper can be placed in the crucible and fired (heated at very high temperature) until all the volatiles and moisture are driven out of the sample residue in the crucible. The "ashless" filter paper is completely burned up in this process. The crucible with the sample and lid is allowed to cool in a desiccator. The crucible and lid with the sample inside is weighed very accurately again only after it has completely cooled to room temperature (higher temperature would cause air currents around the balance giving inaccurate results). The mass of the empty, pre-weighed crucible and lid is subtracted from this result to yield the mass of the completely dried residue in the crucible.
A crucible with a bottom perforated with small holes which is designed specifically for use in filtration, especially for gravimetric analysis as just described, is called a Gooch crucible after its inventor, Frank Austen Gooch.
For completely accurate results, the crucible is handled with clean tongs because fingerprints can add weighable mass to the crucible. Porcelain crucibles are hygroscopic, i. e. they absorb a bit of weighable moisture from the air. For this reason, the porcelain crucible and lid is also pre-fired (pre-heating to high temperature) to constant mass before the pre-weighing. This determines the mass of the completely dry crucible and lid. At least two firings, coolings, and weighings resulting in exactly the same mass are needed to confirm constant (completely dry) mass of the crucible and lid and similarly again for the crucible, lid, and sample residue inside. Since the mass of every crucible and lid is different, the pre-firing/pre-weighing must be done for every new crucible/lid used. The desiccator contains desiccant to absorb moisture from the air inside, so the air inside will be completely dry.
## Use in ash content determination
Ash is the completely unburnable inorganic salts in a sample. A crucible can be similarly used to determine the percentage of ash contained in an otherwise burnable sample of material such as coal, wood, or oil. A crucible and its lid are pre-weighed at constant mass as described above. The sample is added to the completely dry crucible and lid and together they are weighed to determine the mass of the sample by difference. The crucible, lid, and sample are then fired to constant mass to completely burn up the sample, leaving behind only the completely unburnable ash. After cooling in dryness, the crucible, lid, and remaining ash are weighed to find the mass of the ash from the sample by difference. | https://www.wikidoc.org/index.php/Crucible | |
1d14dc19108e634bf607faf2d83ea7e211afd437 | wikidoc | Cryostat | Cryostat
A Cryostat (cryo=cold and stat=stable) is a vessel, similar in construction to a vacuum flask, or Dewar used to maintain cold cryogenic temperatures.
# Cryostat types
## Magnetic Resonance Imaging and Research magnet types
Cryostats used in MRI machines are designed to hold a cryogen, typically helium, in a liquid state with minimal evaporation (boil-off). The liquid helium bath is designed to keep the superconducting magnet's bobbin of superconductive wire in its superconductive state. In this state the wire has no electrical resistance and very large currents are maintained with a low power input. To maintain superconductivity, the bobbin must be kept below its transition temperature by being immersed in the liquid helium. If, for any reason, the wire becomes resistive, i.e. loses superconductivity, a condition known as a "quench", the liquid helium evaporates, instantly raising pressure within the vessel. A burst disk, usually made of carbon, is placed within the chimney or vent pipe so that during a pressure excursion, the gaseous helium can be safely vented out of the MRI suite. Modern MRI cryostats use a mechanical refrigerator (cryocooler) to re-condense the helium gas and return it to the bath, to maintain cryogenic conditions and to conserve helium.
Typically cryostats are manufactured with two vessels, one inside the other. The outer vessel is evacuated with the vacuum acting as a thermal insulator. The inner vessel contains the cryogen and is supported within the outer vessel by structures made from low-conductivity materials. An intermediate shield between the outer and inner vessels intercepts the heat radiated from the outer vessel. This heat is removed by a cryocooler. Older helium cryostats used a liquid nitrogen vessel as this radiation shield and had the liquid helium in an inner, third, vessel. Nowadays few units using multiple cryogens are made with the trend being towards 'cryogen-free' cryostats in which all heat loads are removed by cryocoolers.
## Biological microtome type
In biology, cryostats are used for freezing specimens for sectioning and staining for microscopical examination. The cryostat-microtome is a type of Microtome where the device is located completely within a refrigerated chamber with glass window to enable viewing during the sectioning. To minimize unnecessary warming all necessary mechanical movements of the microtome can be achieved by hand via a wheel mounted outside the chamber. Specimens that are soft at room temperature need to be frozen before sectioning (for example at -20 degrees C).
de:Kryostat
uk:Кріостат | Cryostat
A Cryostat (cryo=cold and stat=stable) is a vessel, similar in construction to a vacuum flask, or Dewar used to maintain cold cryogenic temperatures.
# Cryostat types
## Magnetic Resonance Imaging and Research magnet types
Cryostats used in MRI machines are designed to hold a cryogen, typically helium, in a liquid state with minimal evaporation (boil-off). The liquid helium bath is designed to keep the superconducting magnet's bobbin of superconductive wire in its superconductive state. In this state the wire has no electrical resistance and very large currents are maintained with a low power input. To maintain superconductivity, the bobbin must be kept below its transition temperature by being immersed in the liquid helium. If, for any reason, the wire becomes resistive, i.e. loses superconductivity, a condition known as a "quench", the liquid helium evaporates, instantly raising pressure within the vessel. A burst disk, usually made of carbon, is placed within the chimney or vent pipe so that during a pressure excursion, the gaseous helium can be safely vented out of the MRI suite. Modern MRI cryostats use a mechanical refrigerator (cryocooler) to re-condense the helium gas and return it to the bath, to maintain cryogenic conditions and to conserve helium.
Typically cryostats are manufactured with two vessels, one inside the other. The outer vessel is evacuated with the vacuum acting as a thermal insulator. The inner vessel contains the cryogen and is supported within the outer vessel by structures made from low-conductivity materials. An intermediate shield between the outer and inner vessels intercepts the heat radiated from the outer vessel. This heat is removed by a cryocooler. Older helium cryostats used a liquid nitrogen vessel as this radiation shield and had the liquid helium in an inner, third, vessel. Nowadays few units using multiple cryogens are made with the trend being towards 'cryogen-free' cryostats in which all heat loads are removed by cryocoolers.
## Biological microtome type
In biology, cryostats are used for freezing specimens for sectioning and staining for microscopical examination. The cryostat-microtome is a type of Microtome where the device is located completely within a refrigerated chamber with glass window to enable viewing during the sectioning. To minimize unnecessary warming all necessary mechanical movements of the microtome can be achieved by hand via a wheel mounted outside the chamber. Specimens that are soft at room temperature need to be frozen before sectioning (for example at -20 degrees C).
de:Kryostat
uk:Кріостат
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Cryostat | |
047e1670bb6cecab2b866cb6cbe845274de89545 | wikidoc | Cumulina | Cumulina
Cumulina (December 3 1997-May 5 2000) was a mouse who was the first animal cloned from adult cells that survived to adulthood. She was cloned using the Honolulu technique developed by the Ryuzo Yanagimachi research group, 'Team Yana', at the former campus of the John A. Burns School of Medicine located at the University of Hawai'i at Mānoa. She was a brown Mus musculus or common house mouse. Cumulina was named after the cumulus cells surrounding the developing ovarian follicle in mice. Nuclei from these cells were put into egg cell devoid of their original nuclei in the Honolulu cloning technique. All other mice produced by the Yanagimachi lab are just known by a number.
Cumulina was able to produce two healthy litters. She was retired after the second.
One can now visit Cumulina's preserved remains at the Institute for Biogenesis Research laboratory in Honolulu, Hawaii. The Institute is a part of the John A. Burns School of Medicine.
Some of her descendants have been displayed at the Bishop Museum and the Museum of Science and Industry in Chicago, Illinois. | Cumulina
Cumulina (December 3 1997-May 5 2000) was a mouse who was the first animal cloned from adult cells that survived to adulthood. She was cloned using the Honolulu technique developed by the Ryuzo Yanagimachi research group, 'Team Yana', at the former campus of the John A. Burns School of Medicine located at the University of Hawai'i at Mānoa. She was a brown Mus musculus or common house mouse. Cumulina was named after the cumulus cells surrounding the developing ovarian follicle in mice. Nuclei from these cells were put into egg cell devoid of their original nuclei in the Honolulu cloning technique. All other mice produced by the Yanagimachi lab are just known by a number.[1]
Cumulina was able to produce two healthy litters. She was retired after the second.
One can now visit Cumulina's preserved remains at the Institute for Biogenesis Research laboratory in Honolulu, Hawaii. The Institute is a part of the John A. Burns School of Medicine.
Some of her descendants have been displayed at the Bishop Museum and the Museum of Science and Industry in Chicago, Illinois.[2] | https://www.wikidoc.org/index.php/Cumulina | |
a29182f78eaf5fc10fa6578d37282524fcf2e7e0 | wikidoc | Curcumin | Curcumin
Curcumin is the principal curcuminoid of the Indian curry spice turmeric, the other two curcuminoids being demethoxycurcumin and Bis-demethoxycurcumin.The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in solution. It is also hepatoprotective.
Curcumin can be used for boron quantification in the so-called curcumin method. It reacts with boric acid forming a red colored compound, known as rosocyanine.
Since curcumin is brightly colored, it may be used as a food coloring. As a food additive, its E number is E100.
# Potential medical uses
Curcumin is known for its antitumor, antioxidant, antiarthritic, anti-amyloid and anti-inflammatory properties. Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis. In addition it may be effective in treating malaria, prevention of cervical cancer, and may interefere with the replication of the HIV virus. In HIV, it appears to act by interfering with P300/CREB-binding protein (CBP) of its reverse transcriptase.
Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. Curcuminoids induce glutathione S-transferase and are potent inhibitors of cytochrome P450.
For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of curcumin. Its anticancer effects stem from its ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells. Curcumin can interfere with the activity of the transcription factor NF-κB, which has been linked to a number of inflammatory diseases such as cancer. Indeed, when 0.2% curcumin is added to diet given to rats or mice previously given a carcinogen, it significantly reduces colon carcinogenesis (Data from sixteen scientific articles reported in the Chemoprevention Database). A 2007 report indicates that curcumin may suppress MDM2, an oncogene involved in mechanisms of malignant tumor formation.
A 2004 UCLA-Veterans Affairs study involving genetically altered mice suggests that curcumin might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients and also break up existing plaques associated with the disease.
There is also circumstantial evidence that curcumin improves mental functions; a survey of 1010 Asian people who ate yellow curry and were between the ages of 60 and 93 showed that those who ate the sauce "once every six months" or more had higher MMSE results than those who did not. From a scientific standpoint, though, this does not show whether the curry caused it, or people who had healthy habits also tended to eat the curry, or some completely different relationship.
Little curcumin, when eaten, is absorbed-- 2 grams of curcumin alone resulted in undetectable to very low serum levels. Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increased the absorption of curcumin by 2000%. However, due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications. Some benefits of curcumin, such as the potential protection from colon cancer, may not require systemic absorption. Recently, a polymeric nanoparticle encapsulated formulation of curcumin ("nanocurcumin") has been synthesized which has the potential to bypass many of the shortcomings associated with free curcumin, such as poor solubility and poor systemic bioavailability. Nanocurcumin particles have a size of less than 100 nanometers on average, and demonstrate comparable to superior efficacy compared to free curcumin in human cancer cell line models.
# Risks
Kawanishi et al. (2005) remark that curcumin is a "double-edged sword" having both anti-cancer and carcinogenic effects. Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer. Carcinogenic and LD50 tests in mice and rats, however, have failed to establish a relationship between tumorogenesis and administration of curcumin in turmeric oleoresin at >98% concentrations.
This may prove curcumin medicinally useful as it helps activate p53. When a cell is inhibited by cancer the concentrations of p53 increase, helping cells defend against cancer mechanisms. But it may also suppress p53 levels, preventing cells from initiating defensive mechanisms, a response seen only in certain diseases. | Curcumin
Template:Chembox new
Curcumin is the principal curcuminoid of the Indian curry spice turmeric, the other two curcuminoids being demethoxycurcumin and Bis-demethoxycurcumin.The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in solution.[1] It is also hepatoprotective.[2]
Curcumin can be used for boron quantification in the so-called curcumin method. It reacts with boric acid forming a red colored compound, known as rosocyanine.
Since curcumin is brightly colored, it may be used as a food coloring. As a food additive, its E number is E100.
# Potential medical uses
Curcumin is known for its antitumor, antioxidant, antiarthritic, anti-amyloid and anti-inflammatory properties. Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis.[3] In addition it may be effective in treating malaria, prevention of cervical cancer, and may interefere with the replication of the HIV virus.[4] In HIV, it appears to act by interfering with P300/CREB-binding protein (CBP) of its reverse transcriptase.
Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. Curcuminoids induce glutathione S-transferase and are potent inhibitors of cytochrome P450.
For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of curcumin. Its anticancer effects stem from its ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells. Curcumin can interfere with the activity of the transcription factor NF-κB, which has been linked to a number of inflammatory diseases such as cancer.[5] Indeed, when 0.2% curcumin is added to diet given to rats or mice previously given a carcinogen, it significantly reduces colon carcinogenesis (Data from sixteen scientific articles reported in the Chemoprevention Database). A 2007 report indicates that curcumin may suppress MDM2, an oncogene involved in mechanisms of malignant tumor formation[4].
A 2004 UCLA-Veterans Affairs study involving genetically altered mice suggests that curcumin might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients and also break up existing plaques associated with the disease.[6]
There is also circumstantial evidence that curcumin improves mental functions; a survey of 1010 Asian people who ate yellow curry and were between the ages of 60 and 93 showed that those who ate the sauce "once every six months" or more had higher MMSE results than those who did not.[7] From a scientific standpoint, though, this does not show whether the curry caused it, or people who had healthy habits also tended to eat the curry, or some completely different relationship.
Little curcumin, when eaten, is absorbed-- 2 grams of curcumin alone resulted in undetectable to very low serum levels.[8] Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increased the absorption of curcumin by 2000%[8]. However, due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications. Some benefits of curcumin, such as the potential protection from colon cancer, may not require systemic absorption. Recently, a polymeric nanoparticle encapsulated formulation of curcumin ("nanocurcumin") has been synthesized which has the potential to bypass many of the shortcomings associated with free curcumin, such as poor solubility and poor systemic bioavailability. Nanocurcumin particles have a size of less than 100 nanometers on average, and demonstrate comparable to superior efficacy compared to free curcumin in human cancer cell line models.[9]
# Risks
Kawanishi et al. (2005) remark that curcumin is a "double-edged sword" having both anti-cancer and carcinogenic effects.[10] Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer.[11] Carcinogenic and LD50 tests in mice and rats, however, have failed to establish a relationship between tumorogenesis and administration of curcumin in turmeric oleoresin at >98% concentrations.[12]
This may prove curcumin medicinally useful as it helps activate p53[citation needed]. When a cell is inhibited by cancer the concentrations of p53 increase, helping cells defend against cancer mechanisms[citation needed]. But it may also suppress p53 levels, preventing cells from initiating defensive mechanisms, a response seen only in certain diseases[citation needed]. | https://www.wikidoc.org/index.php/Curcumin | |
c2453465c86bae24649a47fee630949af564fb55 | wikidoc | Cyclin D | Cyclin D
Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. Cyclin D protein is anywhere from 155 (in zebra mussel) to 477 (in Drosophila) amino acids in length.
# Introduction
Once cells reach a critical cell size (and if no mating partner is present in yeast) and if growth factors and mitogens (for multicellular organism) or nutrients (for unicellular organism) are present, cells enter the cell cycle. In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The abundance of cyclins is generally regulated by protein synthesis and degradation through an APC/C dependent pathway.
Cyclin D is one of the major cyclins produced in terms of its functional importance. It interacts with four Cdks: Cdk2, 4, 5, and 6. In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression.
Drosophila and many other organisms only have one cyclin D protein. In mice and humans, two more cyclin D proteins have been identified. The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative amounts expressed differ in various cell types.
# Homologues
The most studied homologues of cyclin D are found in yeast and viruses.
The yeast homologue of cyclin D, referred to as CLN3, interacts with Cdc28 (cell division control protein) during G1.
In viruses, like Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8/Kaposi's sarcoma-associated herpesvirus) cyclin D homologues have acquired new functions in order to manipulate the host cell’s metabolism to the viruses’ benefit.
Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A.
In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D.
# Function
## Cyclins in humans
Growth factors stimulate the Ras/Raf/ERK that induce cyclin D production. One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in cell cycle, among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present.
Even though cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. Despite this, cyclin D has no effect on G1/S transition unless it forms a complex with Cdk 4 or 6.
One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). Rb is an important regulator of genes responsible for progression through the cell cycle, in particular through G1/S phase.
In its un-phosphorylated form, Rb binds a member of E2F family of transcription factors which controls expression of several genes involved in cell cycle progression (example, cyclin E). Rb acts as a repressor, so in complex with E2F it prevents expression of E2F-regulated genes, and this inhibits cells from progressing through G1.
Active cyclin D/Cdk4 and -6 inhibit Rb by partial phosphorylation, reducing its binding to E2F and thereby allowing E2F-mediated activation of the transcription of the cyclin E gene and the cell progresses towards S-phase. Subsequently, cyclin E/Cdk2 fully phosphorylates Rb and completes its inactivation.
# Regulation
## Regulation in humans
Cyclin D is regulated by the downstream pathway of mitogen receptors via the Ras/MAP kinase and the β-catenin-Tcf/LEF pathways and PI3K. The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 and Fos which in turn activate the transcription of the Cdk4, Cdk6 and cyclin D genes, and increase ribosome biogenesis. Rho family GTPases, integrin linked kinase and focal adhesion kinase (FAK) activate cyclin D gene in response to integrin.
p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which negatively regulate CDKs. However they are also promoters of the cyclin D-CDK4/6 complex. Without p27 and p21, cyclin D levels are reduced and the complex is not formed at detectable levels.
In eukaryotes, overexpression of translation initiation factor 4E (eIF4E) leads to an increased level of cyclin D protein and increased amount of cyclin D mRNA outside of the nucleus. This is because eIF4E promotes the export of cyclin D mRNAs out of the nucleus.
Inhibition of cyclin D via i.a. inactivation or degradation leads to cell cycle exit and differentiation.
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. p14, p15, p16, p18). INK4 proteins are activated in response to hyperproliferative stress response that inhibits cell proliferation due to overexpression of e.g. Ras and Myc. Hence, INK4 binds to cyclin D- dependent CDKs and inactivates the whole complex.
Glycogen synthase kinase three beta, GSK3β, causes Cyclin D degradation by inhibitory phosphorylation on threonine 286 of the Cyclin D protein. GSK3β is negatively controlled by the PI3K pathway in form of phosphorylation, which is one of several ways in which growth factors regulate cyclin D. Amount of cyclin D in the cell can also be regulated by transcriptional induction, stabilization of the protein, its translocation to the nucleus and its assembly with Cdk4 and Cdk6.
It has been shown that the inhibition of cyclin D (cyclin D1 and 2, in particular) could result from the induction of WAF1/CIP1/p21 protein by PDT. By inhibiting cyclin D, this induction also inhibits Ckd2 and 6. All these processes combined lead to an arrest of the cell in G0/G1 stage.
There are two ways in which DNA damage affects Cdks. Following DNA damage, cyclin D (cyclin D1) is rapidly and transiently degraded by the proteasome. This degradation causes release of p21 from Cdk4 complexes, which inactivates Cdk2 in a p53-independent manner. Another way in which DNA damage targets Cdks is p53-dependent induction of p21, which inhibits cyclin E-Cdk2 complex. In healthy cells, wild-type p53 is quickly degraded by the proteasome. However, DNA damage causes it to accumulate by making it more stable.
## Regulation in yeast
A simplification in yeast is that all cyclins bind to the same Cdc subunit, the Cdc28.
Cyclins in yeast are controlled by expression, inhibition via CKIs like Far1, and degradation by ubiquitin-mediated proteolysis.
# Role in cancer
Given that many human cancers happen in response to errors in cell cycle regulation and in growth factor dependent intracellular pathways, involvement of cyclin D in cell cycle control and growth factor signaling makes it a possible oncogene. In normal cells overproduction of cyclin D shortens the duration of G1 phase only, and considering the importance of cyclin D in growth factor signaling, defects in its regulation could be responsible for absence of growth regulation in cancer cells. Uncontrolled production of cyclin D affects amounts of cyclin D-Cdk4 complex being formed, which can drive the cell through the G0/S checkpoint, even when the growth factors are not present.
Evidence that cyclin D1 is required for tumorigenesis includes the finding that inactivation of cyclin D1 by anti-sense or gene deletion reduced breast tumor and gastrointestinal tumor growth in vivo. Cyclin D1 overexpression is sufficient for the induction of mammary tumorigenesis, attributed to the induction of cell proliferation, increased cell survival, induction of chromosomal instability, restraint of autophagy and potentially non-canonical functions.
Overexpression is induced as a result of gene amplification, growth factor or oncogene induced expression by Src, Ras, ErbB2, STAT3, STAT5, impaired protein degradation, or chromosomal translocation. Gene amplification is responsible for overproduction of cyclin D protein in bladder cancer and esophageal carcinoma, among others.
In cases of sarcomas, colorectal cancers and melanomas, cyclin D overproduction is noted, however, without the amplification of the chromosomal region that encodes it (chromosome 11q13, putative oncogene PRAD1, which has been identified as a translocation event in case of mantle cell lymphoma).
In parathyroid adenoma, cyclin D hyper-production is caused by chromosomal translocation, which would place expression of cyclin D (more specifically, cyclin D1) under an inappropriate promoter, leading to overexpression. In this case, cyclin D gene has been translocated to the parathyroid hormone gene, and this event caused abnormal levels of cyclin D.
The same mechanisms of overexpression of cyclin D is observed in some tumors of the antibody-producing B cells. Likewise, overexpression of cyclin D protein due to gene translocation is observed in human breast cancer.
Additionally, the development of cancer is also enhanced by the fact that retinoblastoma tumor suppressor protein (Rb), one of the key substrates of cyclin D-Cdk 4/6 complex, is quite frequently mutated in human tumors. In its active form, Rb prevents crossing of the G1 checkpoint by blocking transcription of genes responsible for advances in cell cycle. Cyclin D/Cdk4 complex phosphorylates Rb, which inactivates it and allows for the cell to go through the checkpoint. In the event of abnormal inactivation of Rb, in cancer cells, an important regulator of cell cycle progression is lost. When Rb is mutated, levels of cyclin D and p16INK4 are normal.
Another regulator of passage through G1 restriction point is Cdk inhibitor p16, which is encoded by INK4 gene. P16 functions in inactivating cyclin D/Cdk 4 complex. Thus, blocking transcription of INK4 gene would increase cyclin D/Cdk4 activity, which would in turn result in abnormal inactivation of Rb. On the other hand, in case of cyclin D in cancer cells (or loss of p16INK4) wild-type Rb is retained. Due to the importance of p16INK/cyclin D/Cdk4 or 6/Rb pathway in growth factor signaling, mutations in any of the players involved can give rise to cancer.
# Mutant phenotype
Studies with mutants suggest that cyclins are positive regulators of cell cycle entry. In yeast, expression of any of the three G1 cyclins triggers cell cycle entry. Since cell cycle progression is related to cell size, mutations in Cyclin D and its homologues show a delay in cell cycle entry and thus, cells with variants in cyclin D have bigger than normal cell size at cell division.
p27−/− knockout phenotype show an overproduction of cells because cyclin D is not inhibited anymore, while p27−/− and cyclin D−/− knockouts develop normally. | Cyclin D
Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. Cyclin D protein is anywhere from 155 (in zebra mussel) to 477 (in Drosophila) amino acids in length.[2]
# Introduction
Once cells reach a critical cell size (and if no mating partner is present in yeast) and if growth factors and mitogens (for multicellular organism) or nutrients (for unicellular organism) are present, cells enter the cell cycle. In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The abundance of cyclins is generally regulated by protein synthesis and degradation through an APC/C dependent pathway.
Cyclin D is one of the major cyclins produced in terms of its functional importance. It interacts with four Cdks: Cdk2, 4, 5, and 6. In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression.
Drosophila and many other organisms only have one cyclin D protein. In mice and humans, two more cyclin D proteins have been identified. The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative amounts expressed differ in various cell types.[3]
# Homologues
The most studied homologues of cyclin D are found in yeast and viruses.
The yeast homologue of cyclin D, referred to as CLN3, interacts with Cdc28 (cell division control protein) during G1.
In viruses, like Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8/Kaposi's sarcoma-associated herpesvirus) cyclin D homologues have acquired new functions in order to manipulate the host cell’s metabolism to the viruses’ benefit.[4]
Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A.
In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D.[4][5]
# Function
## Cyclins in humans
Growth factors stimulate the Ras/Raf/ERK that induce cyclin D production.[6] One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in cell cycle, among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present.
Even though cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. Despite this, cyclin D has no effect on G1/S transition unless it forms a complex with Cdk 4 or 6.
One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). Rb is an important regulator of genes responsible for progression through the cell cycle, in particular through G1/S phase.
In its un-phosphorylated form, Rb binds a member of E2F family of transcription factors which controls expression of several genes involved in cell cycle progression (example, cyclin E). Rb acts as a repressor, so in complex with E2F it prevents expression of E2F-regulated genes, and this inhibits cells from progressing through G1.
Active cyclin D/Cdk4 and -6 inhibit Rb by partial phosphorylation, reducing its binding to E2F and thereby allowing E2F-mediated activation of the transcription of the cyclin E gene and the cell progresses towards S-phase. Subsequently, cyclin E/Cdk2 fully phosphorylates Rb and completes its inactivation.[7]
# Regulation
## Regulation in humans
Cyclin D is regulated by the downstream pathway of mitogen receptors via the Ras/MAP kinase and the β-catenin-Tcf/LEF pathways [8] and PI3K.[9] The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 [6] and Fos [10] which in turn activate the transcription of the Cdk4, Cdk6 and cyclin D genes, and increase ribosome biogenesis. Rho family GTPases,[11] integrin linked kinase [12] and focal adhesion kinase (FAK) activate cyclin D gene in response to integrin.[13]
p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which negatively regulate CDKs. However they are also promoters of the cyclin D-CDK4/6 complex. Without p27 and p21, cyclin D levels are reduced and the complex is not formed at detectable levels.[14]
In eukaryotes, overexpression of translation initiation factor 4E (eIF4E) leads to an increased level of cyclin D protein and increased amount of cyclin D mRNA outside of the nucleus.[15] This is because eIF4E promotes the export of cyclin D mRNAs out of the nucleus.[16]
Inhibition of cyclin D via i.a. inactivation or degradation leads to cell cycle exit and differentiation.
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. p14, p15, p16, p18). INK4 proteins are activated in response to hyperproliferative stress response that inhibits cell proliferation due to overexpression of e.g. Ras and Myc. Hence, INK4 binds to cyclin D- dependent CDKs and inactivates the whole complex.[3]
Glycogen synthase kinase three beta, GSK3β, causes Cyclin D degradation by inhibitory phosphorylation on threonine 286 of the Cyclin D protein.[17] GSK3β is negatively controlled by the PI3K pathway in form of phosphorylation, which is one of several ways in which growth factors regulate cyclin D. Amount of cyclin D in the cell can also be regulated by transcriptional induction, stabilization of the protein, its translocation to the nucleus and its assembly with Cdk4 and Cdk6.[18]
It has been shown that the inhibition of cyclin D (cyclin D1 and 2, in particular) could result from the induction of WAF1/CIP1/p21 protein by PDT. By inhibiting cyclin D, this induction also inhibits Ckd2 and 6. All these processes combined lead to an arrest of the cell in G0/G1 stage.[5]
There are two ways in which DNA damage affects Cdks. Following DNA damage, cyclin D (cyclin D1) is rapidly and transiently degraded by the proteasome. This degradation causes release of p21 from Cdk4 complexes, which inactivates Cdk2 in a p53-independent manner. Another way in which DNA damage targets Cdks is p53-dependent induction of p21, which inhibits cyclin E-Cdk2 complex. In healthy cells, wild-type p53 is quickly degraded by the proteasome. However, DNA damage causes it to accumulate by making it more stable.[3]
## Regulation in yeast
A simplification in yeast is that all cyclins bind to the same Cdc subunit, the Cdc28.
Cyclins in yeast are controlled by expression, inhibition via CKIs like Far1, and degradation by ubiquitin-mediated proteolysis.[19]
# Role in cancer
Given that many human cancers happen in response to errors in cell cycle regulation and in growth factor dependent intracellular pathways, involvement of cyclin D in cell cycle control and growth factor signaling makes it a possible oncogene. In normal cells overproduction of cyclin D shortens the duration of G1 phase only, and considering the importance of cyclin D in growth factor signaling, defects in its regulation could be responsible for absence of growth regulation in cancer cells. Uncontrolled production of cyclin D affects amounts of cyclin D-Cdk4 complex being formed, which can drive the cell through the G0/S checkpoint, even when the growth factors are not present.
Evidence that cyclin D1 is required for tumorigenesis includes the finding that inactivation of cyclin D1 by anti-sense [20] or gene deletion [21] reduced breast tumor and gastrointestinal tumor growth [22] in vivo. Cyclin D1 overexpression is sufficient for the induction of mammary tumorigenesis,[23] attributed to the induction of cell proliferation, increased cell survival,[24] induction of chromosomal instability,[25][26] restraint of autophagy [27][28] and potentially non-canonical functions.[29]
Overexpression is induced as a result of gene amplification, growth factor or oncogene induced expression by Src,[30] Ras,[6] ErbB2,[20] STAT3,[31] STAT5,[32] impaired protein degradation, or chromosomal translocation. Gene amplification is responsible for overproduction of cyclin D protein in bladder cancer and esophageal carcinoma, among others.[5]
In cases of sarcomas, colorectal cancers and melanomas, cyclin D overproduction is noted, however, without the amplification of the chromosomal region that encodes it (chromosome 11q13, putative oncogene PRAD1, which has been identified as a translocation event in case of mantle cell lymphoma[33]).
In parathyroid adenoma, cyclin D hyper-production is caused by chromosomal translocation, which would place expression of cyclin D (more specifically, cyclin D1) under an inappropriate promoter, leading to overexpression. In this case, cyclin D gene has been translocated to the parathyroid hormone gene, and this event caused abnormal levels of cyclin D.[5]
The same mechanisms of overexpression of cyclin D is observed in some tumors of the antibody-producing B cells. Likewise, overexpression of cyclin D protein due to gene translocation is observed in human breast cancer.[5][34]
Additionally, the development of cancer is also enhanced by the fact that retinoblastoma tumor suppressor protein (Rb), one of the key substrates of cyclin D-Cdk 4/6 complex, is quite frequently mutated in human tumors. In its active form, Rb prevents crossing of the G1 checkpoint by blocking transcription of genes responsible for advances in cell cycle. Cyclin D/Cdk4 complex phosphorylates Rb, which inactivates it and allows for the cell to go through the checkpoint. In the event of abnormal inactivation of Rb, in cancer cells, an important regulator of cell cycle progression is lost. When Rb is mutated, levels of cyclin D and p16INK4 are normal.[5]
Another regulator of passage through G1 restriction point is Cdk inhibitor p16, which is encoded by INK4 gene. P16 functions in inactivating cyclin D/Cdk 4 complex. Thus, blocking transcription of INK4 gene would increase cyclin D/Cdk4 activity, which would in turn result in abnormal inactivation of Rb. On the other hand, in case of cyclin D in cancer cells (or loss of p16INK4) wild-type Rb is retained. Due to the importance of p16INK/cyclin D/Cdk4 or 6/Rb pathway in growth factor signaling, mutations in any of the players involved can give rise to cancer.[5]
# Mutant phenotype
Studies with mutants suggest that cyclins are positive regulators of cell cycle entry. In yeast, expression of any of the three G1 cyclins triggers cell cycle entry. Since cell cycle progression is related to cell size, mutations in Cyclin D and its homologues show a delay in cell cycle entry and thus, cells with variants in cyclin D have bigger than normal cell size at cell division.[35][36]
p27−/− knockout phenotype show an overproduction of cells because cyclin D is not inhibited anymore, while p27−/− and cyclin D−/− knockouts develop normally.[35] | https://www.wikidoc.org/index.php/Cyclin-D1 | |
37e4cb161a8969e5c468379dc230364bcd59d4f6 | wikidoc | Cyclin A | Cyclin A
Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error-free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.
# Types
Cyclin A was first identified in 1983 in sea urchin embryos. Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila, Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast. The protein exists in both an embryonic form and somatic form. A single cyclin A gene has been identified in Drosophila while Xenopus, mice and humans contain two distinct types of cyclin A: A1, the embryonic-specific form, and A2, the somatic form. Cyclin A1 is prevalently expressed during meiosis and early on in embryogenesis. Cyclin A2 is expressed in dividing somatic cells.
# Role in cell cycle progression
Cyclin A, along with the other members of the cyclin family, regulates cell cycle progression through physically interacting with cyclin-dependent kinases (CDKs), which thereby activates the enzymatic activity of its CDK partner.
## CDK partner association
The interaction between the cyclin box, a region conserved across cyclins, and a region of the CDK, called the PSTAIRE, confers the foundation of the cyclin-CDK complex. Cyclin A is the only cyclin that regulates multiple steps of the cell cycle. Cyclin A can regulate multiple cell cycle steps because it associates with, and thereby activates, two distinct CDKs – CDK2 and CDK1. Depending on which CDK partner cyclin A binds, the cell will continue through the S phase or it will transition from G2 to the M phase. Association of cyclin A with CDK2 is required for passage into S phase while association with CDK1 is required for entry into M phase.
## S phase
Cyclin A resides in the nucleus during S phase where it is involved in the initiation and completion of DNA replication. As the cell passes from G1 into S phase, cyclin A associates with CDK2, replacing cyclin E. Cyclin E is responsible for initiating the assembly of the pre-replication complex. This complex makes chromatin capable of replication. When the amount of cyclin A/CDK2 complex reaches a threshold level, it terminates the assembly of the pre-replication complex made by cyclin E/CDK2. As the amount of Cyclin A/CDK2 complex increases, the complex initiates DNA replication.
Cyclin A has a second function in S phase. In addition to initiating DNA synthesis, Cyclin A ensures that DNA is replicated once per cell cycle by preventing the assembly of additional replication complexes. This is thought to occur through the phosphorylation of particular DNA replication machinery components, such as CDC6, by the cyclin A/CDK2 complex. Since the action of cyclin A/CDK2 inhibits that of cyclin E/CDK2, the sequential activation of cyclin E followed by the activation of cyclin A is important and tightly regulated in S phase.
## G2 / M phase
In late S phase, cyclin A can also associate with CDK1. Cyclin A remains associated with CDK1 from late S into late G2 phase when it is replaced by cyclin B. Cyclin A/CDK1 is thought to be involved in the activation and stabilization of cyclin B/CDK1 complex. Once cyclin B is activated, cyclin A is no longer needed and is subsequently degraded through the ubiquitin pathway. Degradation of cyclin A/CDK1 induces mitotic exit.
Cyclin A/CDK2 complex was thought to be restricted to the nucleus and thus exclusively involved in S phase progression. New research has since debunked this assumption, shedding light on cyclin A/CDK2 migration to the centrosomes in late G2. Cyclin A binds to the mitotic spindle poles in the centrosome however, the mechanism by which the complex is shuttled to the centrosome is not well understood. It is suspected that the presence of cyclin A/CDK2 at the centrosomes may confer a means of regulating the movement of cyclin B/CDK1 to the centrosome and thus the timing of mitotic events.
A study in 2008 provided further evidence of cyclin A/CDK2 complex's role in mitosis. Cells were modified so their CDK2 was inhibited and their cyclin A2 gene was knocked out. These mutants entered mitosis late due to a delayed activation of the cyclin B/CDK1 complex. Coupling of microtubule nucleation in the centrosome with mitotic events in the nucleus was lost in the cyclin A knockout/CDK2 inhibited mutant cells.
Cyclin A has been shown to play a crucial role in the G2/M transition in Drosophila and Xenopus embryos.
# Regulation
Transcription of cyclin A is tightly regulated and synchronized with cell cycle progression. Initiation of transcription of cyclin A is coordinated with passage of the R point, a critical transition point that is required for progression from G1 into S phase. Transcription peaks and plateaus mid-S phase and abruptly declines in late G2.
## E2F and pRb
Transcription of cyclin A is predominantly regulated by the transcription factor E2F in a negative feedback loop. E2F is responsible for initiating the transcription of many critical S phase genes. Cyclin A transcription is off during most of G1 and the begins shortly after the R point.
The retinoblastoma protein (pRb) is involved in the regulation of cyclin A through its interaction with E2F. It exists in two states: hypophosphorylated pRb and hyperphosphorylated pRb. Hypophosphorylated pRb binds E2F, which prevents transcription of cyclin A. The absence of cyclin A prior to the R point is due to the inhibition of E2F by hypophosphorylated pRb. After the cell passes through the R point, cyclin D/E- complexes phosphorylate pRb. Hyperphosphorylated pRb can no longer bind E2F, E2F is released and cyclin A genes, and other crucial genes for S phase, are transcribed.
E2F initiates transcription of cyclin A by de-repressing the promoter. The promoter is bound by a repressor molecule called the cell-cycle-responsive element (CCRE). E2F binds to an E2F binding site on the CCRE, releasing the repressor from the promoter and allowing the transcription of cyclin A. Cyclin A/CDK2 will eventually phosphorylate E2F when cyclin A reaches a certain level, completing the negative feedback loop. Phosphorylation of E2F turns the transcription factor off, providing another level of controlling the transcription of cyclin A.
## p53 and p21
Transcription of cyclin A is indirectly regulated by the tumor suppressor protein p53. P53 is activated by DNA damage and turns on several downstream pathways, including cell cycle arrest. Cell cycle arrest is carried out by the p53-pRb pathway. Activated p53 turns on genes for p21. P21 is a CDK inhibitor that binds to several cyclin/CDK complexes, including cyclin A-CDK2/1 and cyclin D/CDK4, and blocks the kinase activity of CDKs. Activated p21 can bind cyclin D/CDK4 and render it incapable of phosphorylating pRb. PRb remains hypophosphorylated and binds E2F. E2F is unable to activate the transcription of cyclins involved in cell cycle progression, such as cyclin A and the cell cycle is arrested at G1. Cell cycle arrest allows the cell to repair DNA damage before the cell divides and passes damaged DNA to daughter cells. | Cyclin A
Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle.[1] The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle[2] Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error-free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.[1][3]
# Types
Cyclin A was first identified in 1983 in sea urchin embryos.[4] Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila,[5] Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast.[6][7] The protein exists in both an embryonic form and somatic form. A single cyclin A gene has been identified in Drosophila while Xenopus, mice and humans contain two distinct types of cyclin A: A1, the embryonic-specific form, and A2, the somatic form. Cyclin A1 is prevalently expressed during meiosis and early on in embryogenesis. Cyclin A2 is expressed in dividing somatic cells.[7]
# Role in cell cycle progression
Cyclin A, along with the other members of the cyclin family, regulates cell cycle progression through physically interacting with cyclin-dependent kinases (CDKs),[8][9] which thereby activates the enzymatic activity of its CDK partner.[1][2][8]
## CDK partner association
The interaction between the cyclin box, a region conserved across cyclins, and a region of the CDK, called the PSTAIRE, confers the foundation of the cyclin-CDK complex.[10] Cyclin A is the only cyclin that regulates multiple steps of the cell cycle.[7] Cyclin A can regulate multiple cell cycle steps because it associates with, and thereby activates, two distinct CDKs – CDK2 and CDK1.[1] Depending on which CDK partner cyclin A binds, the cell will continue through the S phase or it will transition from G2 to the M phase.[1][3][10] Association of cyclin A with CDK2 is required for passage into S phase while association with CDK1 is required for entry into M phase.[10]
## S phase
Cyclin A resides in the nucleus during S phase where it is involved in the initiation and completion of DNA replication.[1][6][9] As the cell passes from G1 into S phase, cyclin A associates with CDK2, replacing cyclin E. Cyclin E is responsible for initiating the assembly of the pre-replication complex. This complex makes chromatin capable of replication. When the amount of cyclin A/CDK2 complex reaches a threshold level, it terminates the assembly of the pre-replication complex made by cyclin E/CDK2. As the amount of Cyclin A/CDK2 complex increases, the complex initiates DNA replication.[11]
Cyclin A has a second function in S phase. In addition to initiating DNA synthesis, Cyclin A ensures that DNA is replicated once per cell cycle by preventing the assembly of additional replication complexes.[7][11][12] This is thought to occur through the phosphorylation of particular DNA replication machinery components, such as CDC6, by the cyclin A/CDK2 complex.[1][7] Since the action of cyclin A/CDK2 inhibits that of cyclin E/CDK2, the sequential activation of cyclin E followed by the activation of cyclin A is important and tightly regulated in S phase.[7][11]
## G2 / M phase
In late S phase, cyclin A can also associate with CDK1.[1][2][7] Cyclin A remains associated with CDK1 from late S into late G2 phase when it is replaced by cyclin B. Cyclin A/CDK1 is thought to be involved in the activation and stabilization of cyclin B/CDK1 complex.[7][8] Once cyclin B is activated, cyclin A is no longer needed and is subsequently degraded through the ubiquitin pathway.[3][7] Degradation of cyclin A/CDK1 induces mitotic exit.[7]
Cyclin A/CDK2 complex was thought to be restricted to the nucleus and thus exclusively involved in S phase progression. New research has since debunked this assumption, shedding light on cyclin A/CDK2 migration to the centrosomes in late G2.[1][8] Cyclin A binds to the mitotic spindle poles in the centrosome however, the mechanism by which the complex is shuttled to the centrosome is not well understood. It is suspected that the presence of cyclin A/CDK2 at the centrosomes may confer a means of regulating the movement of cyclin B/CDK1 to the centrosome and thus the timing of mitotic events.[1][6][8]
A study in 2008[8] provided further evidence of cyclin A/CDK2 complex's role in mitosis. Cells were modified so their CDK2 was inhibited and their cyclin A2 gene was knocked out. These mutants entered mitosis late due to a delayed activation of the cyclin B/CDK1 complex. Coupling of microtubule nucleation in the centrosome with mitotic events in the nucleus was lost in the cyclin A knockout/CDK2 inhibited mutant cells.
Cyclin A has been shown to play a crucial role in the G2/M transition in Drosophila and Xenopus embryos.[3][6]
# Regulation
Transcription of cyclin A is tightly regulated and synchronized with cell cycle progression.[2][3] Initiation of transcription of cyclin A is coordinated with passage of the R point,[2] a critical transition point that is required for progression from G1 into S phase. Transcription peaks and plateaus mid-S phase and abruptly declines in late G2.[7][12]
## E2F and pRb
Transcription of cyclin A is predominantly regulated by the transcription factor E2F in a negative feedback loop. E2F is responsible for initiating the transcription of many critical S phase genes.[1][3][6] Cyclin A transcription is off during most of G1 and the begins shortly after the R point.[3][7]
The retinoblastoma protein (pRb) is involved in the regulation of cyclin A through its interaction with E2F. It exists in two states: hypophosphorylated pRb and hyperphosphorylated pRb.[2] Hypophosphorylated pRb binds E2F, which prevents transcription of cyclin A. The absence of cyclin A prior to the R point is due to the inhibition of E2F by hypophosphorylated pRb. After the cell passes through the R point, cyclin D/E- complexes phosphorylate pRb. Hyperphosphorylated pRb can no longer bind E2F, E2F is released and cyclin A genes, and other crucial genes for S phase, are transcribed.[2][9][12]
E2F initiates transcription of cyclin A by de-repressing the promoter.[7][12] The promoter is bound by a repressor molecule called the cell-cycle-responsive element (CCRE). E2F binds to an E2F binding site on the CCRE, releasing the repressor from the promoter and allowing the transcription of cyclin A.[5][7] Cyclin A/CDK2 will eventually phosphorylate E2F when cyclin A reaches a certain level, completing the negative feedback loop. Phosphorylation of E2F turns the transcription factor off, providing another level of controlling the transcription of cyclin A.[7]
## p53 and p21
Transcription of cyclin A is indirectly regulated by the tumor suppressor protein p53. P53 is activated by DNA damage and turns on several downstream pathways, including cell cycle arrest. Cell cycle arrest is carried out by the p53-pRb pathway.[13] Activated p53 turns on genes for p21. P21 is a CDK inhibitor that binds to several cyclin/CDK complexes, including cyclin A-CDK2/1 and cyclin D/CDK4, and blocks the kinase activity of CDKs.[9][13] Activated p21 can bind cyclin D/CDK4 and render it incapable of phosphorylating pRb. PRb remains hypophosphorylated and binds E2F. E2F is unable to activate the transcription of cyclins involved in cell cycle progression, such as cyclin A and the cell cycle is arrested at G1.[6][13] Cell cycle arrest allows the cell to repair DNA damage before the cell divides and passes damaged DNA to daughter cells. | https://www.wikidoc.org/index.php/Cyclin_A | |
0b11fb304cb661556fadbcec3b11124776994848 | wikidoc | Cyclin B | Cyclin B
Cyclin B is a member of the cyclin family.
Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, where they fall abruptly due to degradation of cyclin B (Cdk1 is constitutively present). The complex of Cdk and cyclin B is called maturation promoting factor or mitosis promoting factor (MPF).
# Function
Cyclin B is necessary for the progression of the cells into and out of M phase of the cell cycle.
At the end of S phase the phosphatase cdc25c dephosphorylates tyrosine15 and this activates the cyclin B/CDK1 complex. Upon activation the complex is shuttled to the nucleus where it serves to trigger for entry into mitosis. However, if DNA damage is detected alternative proteins are activated which results in the inhibitory phosphorylation of cdc25c and therefore cyclinB/CDK1 is not activated. In order for the cell to progress out of mitosis, the degradation of cyclin B is necessary.
The cyclin B/CDK1 complex also interacts with a variety of other key proteins and pathways which regulate cell growth and progression of mitosis. Cross-talk between many of these pathways links cyclin B levels indirectly to induction of apoptosis. The cyclin B/CDK1 complex plays a critical role in the expression of the survival signal survivin. Survivin is necessary for proper creation of the mitotic spindle which strongly affects cell viability, therefore when cyclin B levels are disrupted cells experience difficulty polarizing. A decrease in survivin levels and the associated mitotic disarray triggers apoptosis via caspase 3 mediated pathway.
# Role in Cancer
Cyclin B plays in integral role in many types of cancer. Hyperplasia (uncontrolled cell growth) is one of the hallmarks of cancer. Because cyclin B is necessary for cells to enter mitosis and therefore necessary for cell division, cyclin B levels are often de-regulated in tumors. When cyclin B levels are elevated, cells can enter M phase prematurely and strict control over cell division is lost, which is a favorable condition for cancer development. On the other hand, if cyclin B levels are depleted the cyclin B/CDK1 complex cannot form, cells cannot enter M phase and cell division slows down. Some anti-cancer therapies have been designed to prevent cyclin B/CDK1 complex formation in cancer cells to slow or prevent cell division. Most of these methods have targeted the CDK1 subunit, but there is an emerging interest in the oncology field to target cyclin B as well.
## As a Biomarker
Cyclin levels can easily be determined through immunohistological analysis of tumor biopsies. The fact that cyclin B is often disregulated in cancer cells makes cyclin B an attractive biomarker. Many studies have been performed to examine cyclin levels in tumors, and it has been shown that levels of cyclin B is a strong indicator of prognosis in many types of cancer. Generally, elevated levels of cyclin B are indicative of more aggressive cancers and a poor prognosis. Immunohistologically assessed levels of cyclin B could determine if women with stage 1, node negative, hormone receptor positive breast cancer were likely to benefit from adjuvant therapy. In general women with this cancer have a very good prognosis, with mortality in 10 years of only 5%. Therefore, it is rare for oncologists to recommend adjuvant chemotherapy in these cases. However, in a small subset of patient this type of cancer is unexpectedly aggressive. These rare patients can be identified through their elevated cyclin B levels. In addition high levels of cyclin B also indicate poor prognosis and lymph node metastasis in gastric cancers. However, not all cancers which overexpress cyclin B are more aggressive. A study in 2009 found that cyclin B overexpression in ovarian cancer indicates that the cancer is unlikely to be malignant while more aggressive ovarian cancers of epithelial cell origin do not show elevated cyclin B.
## Cyclin B and p53
There is strong cross-talk between the pathways regulating cyclin B and the tumor suppressor gene p53. In general levels of p53 and cyclin B are negatively correlated. When p53 build-up triggers cell cycle arrest the levels of downstream proteins p21 and WAF1 are increased which prevents cyclinB/CDK1 complex activation and therefore progression through the cell cycle. It has also been observed that decreasing cyclin B levels in cells increases the levels of functional p53. Therefore, siRNAs for cyclin B may be an effective treatment against cancers where p53 function is inhibited but the gene has not been deleted. In such cases lowering cyclin B levels restores the tumor suppressing function of p53 and also prevents cancer cells from dividing as a consequence of low cyclin B. | Cyclin B
Cyclin B is a member of the cyclin family.
Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle[2] until mitosis, where they fall abruptly due to degradation of cyclin B (Cdk1 is constitutively present).[3] The complex of Cdk and cyclin B is called maturation promoting factor or mitosis promoting factor (MPF).
# Function
Cyclin B is necessary for the progression of the cells into and out of M phase of the cell cycle.
At the end of S phase the phosphatase cdc25c dephosphorylates tyrosine15 and this activates the cyclin B/CDK1 complex. Upon activation the complex is shuttled to the nucleus where it serves to trigger for entry into mitosis.[4] However, if DNA damage is detected alternative proteins are activated which results in the inhibitory phosphorylation of cdc25c and therefore cyclinB/CDK1 is not activated. In order for the cell to progress out of mitosis, the degradation of cyclin B is necessary.[5]
The cyclin B/CDK1 complex also interacts with a variety of other key proteins and pathways which regulate cell growth and progression of mitosis. Cross-talk between many of these pathways links cyclin B levels indirectly to induction of apoptosis. The cyclin B/CDK1 complex plays a critical role in the expression of the survival signal survivin. Survivin is necessary for proper creation of the mitotic spindle which strongly affects cell viability, therefore when cyclin B levels are disrupted cells experience difficulty polarizing.[6] A decrease in survivin levels and the associated mitotic disarray triggers apoptosis via caspase 3 mediated pathway.
# Role in Cancer
Cyclin B plays in integral role in many types of cancer. Hyperplasia (uncontrolled cell growth) is one of the hallmarks of cancer. Because cyclin B is necessary for cells to enter mitosis and therefore necessary for cell division, cyclin B levels are often de-regulated in tumors. When cyclin B levels are elevated, cells can enter M phase prematurely and strict control over cell division is lost, which is a favorable condition for cancer development. On the other hand, if cyclin B levels are depleted the cyclin B/CDK1 complex cannot form, cells cannot enter M phase and cell division slows down. Some anti-cancer therapies have been designed to prevent cyclin B/CDK1 complex formation in cancer cells to slow or prevent cell division. Most of these methods have targeted the CDK1 subunit, but there is an emerging interest in the oncology field to target cyclin B as well.
## As a Biomarker
Cyclin levels can easily be determined through immunohistological analysis of tumor biopsies. The fact that cyclin B is often disregulated in cancer cells makes cyclin B an attractive biomarker. Many studies have been performed to examine cyclin levels in tumors, and it has been shown that levels of cyclin B is a strong indicator of prognosis in many types of cancer.[7] Generally, elevated levels of cyclin B are indicative of more aggressive cancers and a poor prognosis. Immunohistologically assessed levels of cyclin B could determine if women with stage 1, node negative, hormone receptor positive breast cancer were likely to benefit from adjuvant therapy.[8] In general women with this cancer have a very good prognosis, with mortality in 10 years of only 5%. Therefore, it is rare for oncologists to recommend adjuvant chemotherapy in these cases. However, in a small subset of patient this type of cancer is unexpectedly aggressive. These rare patients can be identified through their elevated cyclin B levels. In addition high levels of cyclin B also indicate poor prognosis and lymph node metastasis in gastric cancers.[9] However, not all cancers which overexpress cyclin B are more aggressive. A study in 2009 found that cyclin B overexpression in ovarian cancer indicates that the cancer is unlikely to be malignant while more aggressive ovarian cancers of epithelial cell origin do not show elevated cyclin B.[10]
## Cyclin B and p53
There is strong cross-talk between the pathways regulating cyclin B and the tumor suppressor gene p53. In general levels of p53 and cyclin B are negatively correlated. When p53 build-up triggers cell cycle arrest the levels of downstream proteins p21 and WAF1 are increased which prevents cyclinB/CDK1 complex activation and therefore progression through the cell cycle.[11] It has also been observed that decreasing cyclin B levels in cells increases the levels of functional p53.[12] Therefore, siRNAs for cyclin B may be an effective treatment against cancers where p53 function is inhibited but the gene has not been deleted. In such cases lowering cyclin B levels restores the tumor suppressing function of p53 and also prevents cancer cells from dividing as a consequence of low cyclin B. | https://www.wikidoc.org/index.php/Cyclin_B | |
c805f2cb7b0c2d0c0bfe2e26bbe5c4d8ac4f304d | wikidoc | Cyclin E | Cyclin E
Cyclin E is a member of the cyclin family.
Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase.
# Functions of Cyclin E
Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple cellular processes by phosphorylating numerous downstream proteins.
Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition. Cyclin E/CDK2 phosphorylates retinoblastoma protein (Rb) to promote G1 progression. Hyper-phosphorylated Rb will no longer interact with E2F transcriptional factor, thus release it to promote expression of genes that drive cells to S phase through G1 phase. Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively. Smad3, a key mediator of TGF-β pathway which inhibits cell cycle progression, can be phosphorylated by cyclin E/CDK2. The phosphorylation of Smad3 by cyclin E/CDK2 inhibits its transcriptional activity and ultimately facilitates cell cycle progression. CBP/p300 and E2F-5 are also substrates of cyclin E/CDK2. Phosphorylation of these two proteins stimulates the transcriptional events during cell cycle progression. Cyclin E/CDK2 can phosphorylate p220(NPAT) to promote histone gene transcription during cell cycle progression.
Apart from the function in cell cycle progression, cyclin E/CDK2 plays a role in the centrosome cycle. This function is performed by phosphorylating nucleophosmin (NPM). Then NPM is released from binding to an unduplicated centrosome, thereby triggering duplication. CP110 is another cyclin E/CDK2 substrate which involves in centriole duplication and centrosome separation. Cyclin E/CDK2 has also been shown to regulate the apoptotic response to DNA damage via phosphorylation of FOXO1.
# Cyclin E and Cancer
Over-expression of cyclin E correlates with tumorigenesis. It is involved in various types of cancers, including breast, colon, bladder, skin and lung cancer. DNA copy-number amplification of cyclin E1 is involved in brain cancer. Besides that, dysregulated cyclin E activity causes cell lineage-specific abnormalities, such as impaired maturation due to increased cell proliferation and apoptosis or senescence.
Several mechanisms lead to the deregulated expression of cyclin E. In most cases, gene amplification causes the overexpression. Proteosome caused defected degradation is another mechanism. Loss-of-function mutations of FBXW7 were found in several cancer cells. FBXW7 encodes F-box proteins which target cyclin E for ubiquitination. Cyclin E overexpression can lead to G1 shortening, decrease in cell size or loss of serum requirement for proliferation.
Dysregulation of cyclin E occurs in 18-22% of the breast cancers. Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor. Low molecular weight cyclin E isoforms have been shown to be of great pathogenetic and prognostic importance for breast cancer. These isoforms are resistant to CKIs, bind with CDK2 more efficiently and can stimulate the cell cycle progression more efficiently. They are proved to be a remarkable marker of the prognosis of early-stage-node negative breast cancer. Importantly, a recent research pointed out cyclin E overexpression is a mechanism of Trastuzumab resistance in HER2+ breast cancer patients. Thus, co-treatment of trastuzumab with CDK2 inhibitors may be a valid strategy.
Cyclin E overexpression is implicated in carcinomas at various sites along the gastrointestinal tract. Among these carcinomas, cyclin E appears to be more important in stomach and colon cancer. Cyclin E overexpression was found in 50-60% of gastric adenomas and adenocarcinomas. In ~10% of colorectal carcinomas, cyclin E gene amplification is found, sometimes together with CDK2 gene amplification.
Cyclin E is also a useful prognostic marker for lung cancer. There is significant association between cyclin E over-expression and the prognosis of lung cancer. It is believed increased expression of cyclin E correlated with poorer prognosis. | Cyclin E
Cyclin E is a member of the cyclin family.
Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase.
# Functions of Cyclin E
Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple cellular processes by phosphorylating numerous downstream proteins.
Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition. Cyclin E/CDK2 phosphorylates retinoblastoma protein (Rb) to promote G1 progression. Hyper-phosphorylated Rb will no longer interact with E2F transcriptional factor, thus release it to promote expression of genes that drive cells to S phase through G1 phase.[1] Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively. Smad3, a key mediator of TGF-β pathway which inhibits cell cycle progression, can be phosphorylated by cyclin E/CDK2. The phosphorylation of Smad3 by cyclin E/CDK2 inhibits its transcriptional activity and ultimately facilitates cell cycle progression.[2] CBP/p300 and E2F-5 are also substrates of cyclin E/CDK2. Phosphorylation of these two proteins stimulates the transcriptional events during cell cycle progression.[3] Cyclin E/CDK2 can phosphorylate p220(NPAT) to promote histone gene transcription during cell cycle progression.[4]
Apart from the function in cell cycle progression, cyclin E/CDK2 plays a role in the centrosome cycle. This function is performed by phosphorylating nucleophosmin (NPM). Then NPM is released from binding to an unduplicated centrosome, thereby triggering duplication.[5] CP110 is another cyclin E/CDK2 substrate which involves in centriole duplication and centrosome separation.[6] Cyclin E/CDK2 has also been shown to regulate the apoptotic response to DNA damage via phosphorylation of FOXO1.[7]
# Cyclin E and Cancer
Over-expression of cyclin E correlates with tumorigenesis. It is involved in various types of cancers, including breast, colon, bladder, skin and lung cancer.[8] DNA copy-number amplification of cyclin E1 is involved in brain cancer.[9][10] Besides that, dysregulated cyclin E activity causes cell lineage-specific abnormalities, such as impaired maturation due to increased cell proliferation and apoptosis or senescence.[11][12]
Several mechanisms lead to the deregulated expression of cyclin E. In most cases, gene amplification causes the overexpression.[13] Proteosome caused defected degradation is another mechanism. Loss-of-function mutations of FBXW7 were found in several cancer cells. FBXW7 encodes F-box proteins which target cyclin E for ubiquitination.[14] Cyclin E overexpression can lead to G1 shortening, decrease in cell size or loss of serum requirement for proliferation.
Dysregulation of cyclin E occurs in 18-22% of the breast cancers. Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor.[15] Low molecular weight cyclin E isoforms have been shown to be of great pathogenetic and prognostic importance for breast cancer.[16] These isoforms are resistant to CKIs, bind with CDK2 more efficiently and can stimulate the cell cycle progression more efficiently. They are proved to be a remarkable marker of the prognosis of early-stage-node negative breast cancer.[17] Importantly, a recent research pointed out cyclin E overexpression is a mechanism of Trastuzumab resistance in HER2+ breast cancer patients. Thus, co-treatment of trastuzumab with CDK2 inhibitors may be a valid strategy.[18]
Cyclin E overexpression is implicated in carcinomas at various sites along the gastrointestinal tract. Among these carcinomas, cyclin E appears to be more important in stomach and colon cancer. Cyclin E overexpression was found in 50-60% of gastric adenomas and adenocarcinomas.[19] In ~10% of colorectal carcinomas, cyclin E gene amplification is found, sometimes together with CDK2 gene amplification.[20]
Cyclin E is also a useful prognostic marker for lung cancer. There is significant association between cyclin E over-expression and the prognosis of lung cancer. It is believed increased expression of cyclin E correlated with poorer prognosis.[21] | https://www.wikidoc.org/index.php/Cyclin_E | |
86066ba2ba9e1a30d4e97b94c6b71257ae37e340 | wikidoc | Cyclopia | Cyclopia
# Overview
Cyclopia (also cyclocephaly or synophthalmia) is a rare form of holoprosencephaly and is a congenital disorder (birth defect) characterized by the failure of the embryonic prosencephalon to properly divide the orbits of the eye into two cavities. Its incidence is 1 in 16,000 in born animals, and 1 in 250 in embryos.
# Presentation
Typically, the nose is either missing or replaced with a non-functioning nose in the form of a proboscis. Although cyclopia is very rare, several cyclopic human babies are preserved in medical museums (e.g The Vrolik Museum, Amsterdam). There are also two known cases of children with Down Syndrome being born with one eye.
Some extreme cases of cyclopia have been documented in cats. In such cases, the nose and mouth fail to form, resulting in suffocation shortly after birth.
# Causes
Genetic problems or toxins can cause problems in the embryonic forebrain-dividing process.
One highly teratogenic alkaloid toxin that can cause cyclopia is cyclopamine or 2-deoxyjervine, found in the plant Veratrum californicum (also known as corn lily or vetch weed). The mistake of ingesting Veratrum californicum while pregnant is often due to the fact that hellebore, a plant with which it is easily confused, is recommended as a natural treatment for vomiting, cramps, and poor circulation, three conditions that are quite common in pregnant women.
# Notable cases
An old description of a colt apparently suffering from cyclopia reads:
First, That it had no sign of any Nose in the usual place, nor had it any, in any other place of the Head, unless the double Bagg CC that grew out of the midst of the forehead, were some rudiment of it.
Next, That the two Eyes were united into one Double Eye which was placed just in the middle of the Brow.
In 2005, a kitten with cyclopia, "Cy", was born in the United States and died about one day after birth. | Cyclopia
# Overview
Cyclopia (also cyclocephaly or synophthalmia) is a rare form of holoprosencephaly and is a congenital disorder (birth defect) characterized by the failure of the embryonic prosencephalon to properly divide the orbits of the eye into two cavities. Its incidence is 1 in 16,000 in born animals, and 1 in 250 in embryos.[1]
# Presentation
Typically, the nose is either missing or replaced with a non-functioning nose in the form of a proboscis. Although cyclopia is very rare, several cyclopic human babies are preserved in medical museums (e.g The Vrolik Museum, Amsterdam).[2] There are also two known cases of children with Down Syndrome being born with one eye.[3]
Some extreme cases of cyclopia have been documented in cats. In such cases, the nose and mouth fail to form, resulting in suffocation shortly after birth.[4]
# Causes
Genetic problems or toxins can cause problems in the embryonic forebrain-dividing process.[5]
One highly teratogenic alkaloid toxin that can cause cyclopia is cyclopamine or 2-deoxyjervine, found in the plant Veratrum californicum (also known as corn lily or vetch weed). The mistake of ingesting Veratrum californicum while pregnant is often due to the fact that hellebore, a plant with which it is easily confused, is recommended as a natural treatment for vomiting, cramps, and poor circulation, three conditions that are quite common in pregnant women.[6]
# Notable cases
An old description of a colt apparently suffering from cyclopia reads:
First, That it had no sign of any Nose in the usual place, nor had it any, in any other place of the Head, unless the double Bagg CC that grew out of the midst of the forehead, were some rudiment of it.
Next, That the two Eyes were united into one Double Eye which was placed just in the middle of the Brow.
[7]
In 2005, a kitten with cyclopia, "Cy", was born in the United States and died about one day after birth.[8] | https://www.wikidoc.org/index.php/Cyclopia | |
56ba7602f287acd8c9b3cf187afe75e85361fa57 | wikidoc | Pemoline | Pemoline
# Overview
Pemoline (sold as Cylert) is a medication used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug.
Pemoline has some advantages over other stimulants in that it does not reduce the appetite or cause dry mouth.
# Hepatotoxicity and discontinuation
In some patients Pemoline is suspected of causing hepatotoxicity, so regular liver tests are performed on those treated with it. Since receiving FDA approval in 1975, it has been linked with 21 cases of liver failure, of which 13 resulted in liver replacement or death. In 2005, the Food and Drug Administration (FDA) withdrew approval for pemoline due to pressure from certain public advocacy groups, including Public Citizen. The patient support group "Narcolepsy Network" tried to persuade the FDA not to ban it, on the grounds that some patients find all other treatments ineffective or to have debilitating side effects. The medication was used by an estimated 10,000 Americans afflicted with narcolepsy. A more potent analogue of pemoline, 4-methylaminorex has appeared as a black market drug with abuse potential similar to methamphetamine.
In March 2005, Abbott Laboratories (Cylert marketer) had discontinued the production of Cylert arguing economic reasons. | Pemoline
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pemoline (sold as Cylert) is a medication used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug.[1]
Pemoline has some advantages over other stimulants in that it does not reduce the appetite or cause dry mouth.
# Hepatotoxicity and discontinuation
In some patients Pemoline is suspected of causing hepatotoxicity, so regular liver tests are performed on those treated with it. Since receiving FDA approval in 1975, it has been linked with 21 cases of liver failure, of which 13 resulted in liver replacement or death. In 2005, the Food and Drug Administration (FDA) withdrew approval for pemoline due to pressure from certain public advocacy groups, including Public Citizen. The patient support group "Narcolepsy Network"[2] tried to persuade the FDA not to ban it, on the grounds that some patients find all other treatments ineffective or to have debilitating side effects. The medication was used by an estimated 10,000 Americans afflicted with narcolepsy. A more potent analogue of pemoline, 4-methylaminorex has appeared as a black market drug with abuse potential similar to methamphetamine.
In March 2005, Abbott Laboratories (Cylert marketer) had discontinued the production of Cylert arguing economic reasons.
Template:Pharma-stub | https://www.wikidoc.org/index.php/Cylert | |
32f69305812cf14b356866674ed9511a2d1ea64d | wikidoc | Cytokine | Cytokine
Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. These chemical signals are similar to hormones and neurotransmitters and are used to allow one cell to communicate with another. The cytokine family consists mainly of smaller water-soluble proteins and glycoproteins (proteins with an added sugar chain) with a mass of between 8 and 30 kDa. While hormones are released from specific organs into the blood and neurotransmitters are released by nerves, cytokines are released by many types of cells. They are particularly important in both innate and adaptive immune responses. Due to their central role in the immune system, cytokines are involved in a variety of immunological, inflammatory and infectious diseases. However, not all their functions are limited to the immune system, as they are also involved in several developmental processes during embryogenesis.
Cytokines are produced by a wide variety of cell types (both haemopoietic and non-haemopoietic) and can have effects on both nearby cells or throughout the organism. Sometimes these effects are strongly dependent on the presence of other chemicals and cytokines.
# Effects
Each cytokine binds to a specific cell-surface receptor. Subsequent cascades of intracellular signalling then alter cell functions. This may include the upregulation and/or downregulation of several genes and their transcription factors, in turn resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition.
The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence and abundance of the complementary receptor on the cell surface, and downstream signals activated by receptor binding; these last two factors can vary by cell type. Interestingly, cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions.
Generalization of functions is not possible with cytokines; nonetheless, their actions may be comfortably grouped as:
- autocrine, if the cytokine acts on the cell that secretes it
- paracrine, if the action is restricted to the immediate vicinity of a cytokine's secretion
- endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma) to affect different tissues.
Cytokines binding to antibodies paradoxically have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses and perhaps fewer side effects.
Overstimulation of cytokines can trigger a dangerous syndrome known as a cytokine storm; this may have been the cause of severe adverse events during a clinical trial of TGN1412.
# Nomenclature
Cytokines have been variously named as lymphokines, interleukins and chemokines, based on their presumed function, cell of secretion or target of action. Because cytokines are characterized by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete.
- The term interleukin was initially used by researchers for those cytokines whose presumed targets are principally leukocytes. It is now used largely for designation of newer cytokine molecules discovered every day and bears little relation to their presumed function.
- The term chemokine refers to a specific class of cytokines that mediates chemoattraction (chemotaxis) between cells.
Of note, IL-8 (interleukin-8) is the only chemokine originally named an interleukin.
# Classification
## Structural
Structural homology has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types:
- The four α-helix bundle family - Member cytokines have three-dimensional structures with four bundles of α-helices. This family in turn is divided into three sub-families:
the IL-2 subfamily
the interferon (IFN) subfamily
the IL-10 subfamily
The first of these three subfamilies is the largest. It contains several non-immunological cytokines including erythropoietin (EPO) and thrombopoietin (THPO). Alternatively, four α-helix bundle cytokines can be grouped into long chain and short chain cytokines.
- the IL-2 subfamily
- the interferon (IFN) subfamily
- the IL-10 subfamily
- the IL-1 family - It primarily includes IL-1 and IL-18.
- the IL-17 family - It has yet to be completely characterized, though member cytokines have a specific effect in promoting proliferation of T-cells that cause cytotoxic effects.
- Chemokines
## Functional
A more clinically and experimentally useful classification divides immunological cytokines into those that promote the proliferation and functioning of helper T-cells, type 1 ( IFN-γ etc.) and type 2 (IL-4, IL-10, IL-13, TGF-β etc.), respectively.
A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit the effects of those in the other. This tendency is under intensive study for its possible role in the pathogenesis of autoimmune disorders.
# Cytokine receptors
In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors have now been directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleiomorphism of cytokines are in fact a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful.
A classification of cytokine receptors based on their three-dimensional structure has therefore been attempted. (It must be noted that such a classification, though seemingly cumbersome, provides with several unique perspectives for attractive pharmacotherapeutic targets.)
- Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural homology with immunoglobulins (antibodies), cell adhesion molecules, and even some cytokines. Examples: IL-1 receptor types.
- Haemopoietic Growth Factor (type 1) family, whose members have certain conserved motifs in their extracellular amino-acid domain. The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID).
- Interferon (type 2) family, whose members are receptors for IFN β and γ.
- Tumour Necrosis Factor (TNF) (type 3) family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like CD40, CD27 and CD30, besides the ligands on which the family is named (TNF).
- Seven transmembrane helix family, the ubiquitous receptor type of the animal kingdom. All G-protein coupled receptors (for hormones and neurotransmitters) belong to this family. It is important to note that chemokine receptors, two of which act as binding proteins for HIV (CXCR4 and CCR5), also belong to this family.
# Cysteine-knot cytokines
Members of the transforming growth factor beta superfamily belong to this group, including TGF-β1, TGF-β2 and TGF-β3. | Cytokine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. These chemical signals are similar to hormones and neurotransmitters and are used to allow one cell to communicate with another. The cytokine family consists mainly of smaller water-soluble proteins and glycoproteins (proteins with an added sugar chain) with a mass of between 8 and 30 kDa. While hormones are released from specific organs into the blood and neurotransmitters are released by nerves, cytokines are released by many types of cells. They are particularly important in both innate and adaptive immune responses. Due to their central role in the immune system, cytokines are involved in a variety of immunological, inflammatory and infectious diseases. However, not all their functions are limited to the immune system, as they are also involved in several developmental processes during embryogenesis.
Cytokines are produced by a wide variety of cell types (both haemopoietic and non-haemopoietic) and can have effects on both nearby cells or throughout the organism. Sometimes these effects are strongly dependent on the presence of other chemicals and cytokines.
# Effects
Each cytokine binds to a specific cell-surface receptor. Subsequent cascades of intracellular signalling then alter cell functions. This may include the upregulation and/or downregulation of several genes and their transcription factors, in turn resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition.
The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence and abundance of the complementary receptor on the cell surface, and downstream signals activated by receptor binding; these last two factors can vary by cell type. Interestingly, cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions.
Generalization of functions is not possible with cytokines; nonetheless, their actions may be comfortably grouped as:
- autocrine, if the cytokine acts on the cell that secretes it
- paracrine, if the action is restricted to the immediate vicinity of a cytokine's secretion
- endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma) to affect different tissues.
Cytokines binding to antibodies paradoxically have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses and perhaps fewer side effects.
Overstimulation of cytokines can trigger a dangerous syndrome known as a cytokine storm; this may have been the cause of severe adverse events during a clinical trial of TGN1412.
# Nomenclature
Cytokines have been variously named as lymphokines, interleukins and chemokines, based on their presumed function, cell of secretion or target of action. Because cytokines are characterized by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete.
- The term interleukin was initially used by researchers for those cytokines whose presumed targets are principally leukocytes. It is now used largely for designation of newer cytokine molecules discovered every day and bears little relation to their presumed function.
- The term chemokine refers to a specific class of cytokines that mediates chemoattraction (chemotaxis) between cells.
Of note, IL-8 (interleukin-8) is the only chemokine originally named an interleukin.
# Classification
## Structural
Structural homology has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types:
- The four α-helix bundle family - Member cytokines have three-dimensional structures with four bundles of α-helices. This family in turn is divided into three sub-families:
the IL-2 subfamily
the interferon (IFN) subfamily
the IL-10 subfamily
The first of these three subfamilies is the largest. It contains several non-immunological cytokines including erythropoietin (EPO) and thrombopoietin (THPO). Alternatively, four α-helix bundle cytokines can be grouped into long chain and short chain cytokines.
- the IL-2 subfamily
- the interferon (IFN) subfamily
- the IL-10 subfamily
- the IL-1 family - It primarily includes IL-1 and IL-18.
- the IL-17 family - It has yet to be completely characterized, though member cytokines have a specific effect in promoting proliferation of T-cells that cause cytotoxic effects.
- Chemokines
## Functional
A more clinically and experimentally useful classification divides immunological cytokines into those that promote the proliferation and functioning of helper T-cells, type 1 ( IFN-γ etc.) and type 2 (IL-4, IL-10, IL-13, TGF-β etc.), respectively.
A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit the effects of those in the other. This tendency is under intensive study for its possible role in the pathogenesis of autoimmune disorders.
# Cytokine receptors
In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors have now been directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleiomorphism of cytokines are in fact a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful.
A classification of cytokine receptors based on their three-dimensional structure has therefore been attempted. (It must be noted that such a classification, though seemingly cumbersome, provides with several unique perspectives for attractive pharmacotherapeutic targets.)
- Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural homology with immunoglobulins (antibodies), cell adhesion molecules, and even some cytokines. Examples: IL-1 receptor types.
- Haemopoietic Growth Factor (type 1) family, whose members have certain conserved motifs in their extracellular amino-acid domain. The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID).
- Interferon (type 2) family, whose members are receptors for IFN β and γ.
- Tumour Necrosis Factor (TNF) (type 3) family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like CD40, CD27 and CD30, besides the ligands on which the family is named (TNF).
- Seven transmembrane helix family, the ubiquitous receptor type of the animal kingdom. All G-protein coupled receptors (for hormones and neurotransmitters) belong to this family. It is important to note that chemokine receptors, two of which act as binding proteins for HIV (CXCR4 and CCR5), also belong to this family.
# Cysteine-knot cytokines
Members of the transforming growth factor beta superfamily belong to this group, including TGF-β1, TGF-β2 and TGF-β3. | https://www.wikidoc.org/index.php/Cytokine | |
b26e413b3c199930dd64c8e131dadabde47bdf6b | wikidoc | Fructose | Fructose
# Overview
Fructose (or levulose) is a simple sugar (monosaccharide) found in many foods and is one of the three most important blood sugars along with glucose and galactose. Honey, tree fruits, berries, melons, and some root vegetables, such as beets, sweet potatoes, parsnips, and onions, contain fructose, usually in combination with sucrose and glucose. Fructose is also derived from the digestion of sucrose, a disaccharide consisting of glucose and fructose that is broken down by glycoside hydrolase enzymes during digestion. Fructose is the sweetest naturally occurring sugar, estimated to be twice as sweet as sucrose.
Fructose is often recommended for, and consumed by, people with diabetes mellitus or hypoglycemia, because it has a very low glycemic index (GI) relative to cane sugar (sucrose). However, this benefit is tempered by concern that fructose may have an adverse effect on plasma lipid and uric acid levels, and the resulting higher blood levels of fructose can be damaging to proteins (see below). The low GI is due to the unique and lengthy metabolic pathway of fructose, which involves phosphorylation and a multi-step enzymatic process in the liver. See health effects and glycation for further information.
# Structure
D-Fructose, also known as levulose, is a levorotatory monosaccharide and an isomer of glucose (C6H12O6). The chemical composition of fructose is (C6H12O6). Pure fructose has a sweet taste similar to cane sugar, but with a "fruity" aroma. Although fructose is a hexose (6 carbon sugar), it generally exists as a 5-member hemiketal ring (a furanose). This structure is responsible for the long metabolic pathway and high reactivity compared to glucose.
## Isomerism
D-Fructose has the same configuration at its penultimate carbon as D-glyceraldehyde. Fructose is sweeter than glucose because of its structure.
# Metabolism
Shown below is a diagram depicting the fructose metabolism.
# Health effects
Fructose absorption occurs via the GLUT-5 (fructose only) transporter, and the GLUT2 transporter, for which it competes with glucose and galactose. A deficiency of GLUT 5 may result in excess fructose carried into the lower intestine. There, it can provide nutrients for the existing gut flora, which produce gas. It may also cause water retention in the intestine. These effects may lead to bloating, excessive flatulence, loose stools, and even diarrhea depending on the amounts eaten and other factors.
Excess fructose consumption has been hypothesized to possibly cause insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic syndrome. However, unlike animal experiments, some human experiments have failed to show a correlation between fructose consumption and obesity. Short term tests, lack of dietary control, and lack of a non-fructose consuming control group are all confounding factors in human experiments. However, there are now a number of reports showing correlation of fructose consumption to obesity, especially central obesity which is generally regarded as the most dangerous type.
There is a concern with Diabetic 1 patients and the apparent low GI of fructose. Fructose gives as high blood sugar spike as that obtained with glucose. In fact, GI only applies to high starch foods. The basic GI definition is chemically incorrect. This is because the body blood glucose response is "standardized" with 50g of glucose, while the GI Researchers use 50g of digestible carbohydrate as a reference quantity. Although all simple sugars are isomers, each have separate chemical properties.
This is illustrated with pure fructose. In a study from The American Journal of Clinical Nutrition, "fructose given alone increased the blood glucose almost as much as a similar amount of glucose (78% of the glucose-alone area)".
A study in mice suggests that fructose increases obesity.
One study concluded that fructose "produced significantly higher fasting plasma triacylglycerol values than did the glucose diet in men" and "if plasma triacylglycerols are a risk factor for cardiovascular disease, then diets high in fructose may be undesirable". Bantle et al. "noted the same effects in a study of 14 healthy volunteers who sequentially ate a high-fructose diet and one almost devoid of the sugar."
Studies that have compared high fructose corn syrup (an ingredient in soft drinks sold in the US) to sucrose (common cane sugar) find that they have essentially identical physiological effects. For instance, Melanson et al (2006), studied the effects of HFCS and sucrose sweetened drinks on blood glucose, insulin, leptin, and ghrelin levels. They found no significant differences in any of these parameters. This is not surprising since sucrose is a disaccharide which digests to 50% glucose and 50% fructose; while the high fructose corn syrup most commonly used on soft drinks is 55% fructose.
Fructose also chelates minerals in the blood. This effect is especially important with micronutrients such as copper, chromium and zinc. Since these solutes are normally present in small quantities, chelation of small numbers of ions may lead to deficiency diseases, immune system impairment and even insulin resistance, a component of type II diabetes.
Fructose is often recommended for diabetics due to its glycemic index being significantly lower than both glucose, sucrose and starches.
"The medical profession thinks fructose is better for diabetics than sugar," says Meira Field, Ph.D., a research chemist at the USDA, "but every cell in the body can metabolize glucose. However, all fructose must be metabolized in the liver. The livers of the rats on the high fructose diet looked like the livers of alcoholics, plugged with fat and cirrhotic." This is not entirely true as certain other tissues do use fructose directly, notably the cells of the intestine, and sperm cells (for which fructose is the main energy source).
Fructose is a reducing sugar, as are all monosaccharides. The spontaneous addition of single sugar molecules to proteins, known as glycation, is a significant cause of damage in diabetics. Fructose appears to be as dangerous as glucose in this regard and so does not seem to be a better answer for diabetes for this reason alone. This may be an important contribution to senescence and many age-related chronic diseases.
Fructose is used as a substitute for sucrose (composed of one unit each of fructose and glucose linked together with a relatively weak glycosidic bond) because it is less expensive and has little effect on measured blood glucose levels. Often, fructose is consumed as high fructose corn syrup, which is corn syrup (glucose) that has been enzymatically treated by the enzyme glucose isomerase. This enzyme converts a portion of the glucose into fructose thus making it sweeter. This is done to such a degree as to yield corn syrup with an equivalent sweetness to sucrose by weight. While most carbohydrates have around the same amount of calories, fructose is sweeter and manufacturers can use less of it to get the same result.
The free fructose present in fruits, their juice, and honey is responsible for the greater sweetness of these natural sugar sources.
Unlike glucose, fructose is almost entirely metabolized in the liver. When fructose reaches the liver, says Dr. William J. Whelan, a biochemist at the University of Miami School of Medicine, "the liver goes bananas and stops everything else to metabolize the fructose." Eating fructose as compared to glucose results in lower circulating insulin levels, leptin, and ghrelin levels postprandially. These hormones are implicated in the control of appetite and satiety, and it is hypothesized that eating lots of fructose could increase the likelihood of weight gain. | Fructose
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Fructose (or levulose) is a simple sugar (monosaccharide) found in many foods and is one of the three most important blood sugars along with glucose and galactose. Honey, tree fruits, berries, melons, and some root vegetables, such as beets, sweet potatoes, parsnips, and onions, contain fructose, usually in combination with sucrose and glucose. Fructose is also derived from the digestion of sucrose, a disaccharide consisting of glucose and fructose that is broken down by glycoside hydrolase enzymes during digestion. Fructose is the sweetest naturally occurring sugar, estimated to be twice as sweet as sucrose.
Fructose is often recommended for, and consumed by, people with diabetes mellitus or hypoglycemia, because it has a very low glycemic index (GI) relative to cane sugar (sucrose). However, this benefit is tempered by concern that fructose may have an adverse effect on plasma lipid and uric acid levels, and the resulting higher blood levels of fructose can be damaging to proteins (see below). The low GI is due to the unique and lengthy metabolic pathway of fructose, which involves phosphorylation and a multi-step enzymatic process in the liver. See health effects and glycation for further information.
# Structure
D-Fructose, also known as levulose, is a levorotatory monosaccharide and an isomer of glucose (C6H12O6). The chemical composition of fructose is (C6H12O6). Pure fructose has a sweet taste similar to cane sugar, but with a "fruity" aroma. Although fructose is a hexose (6 carbon sugar), it generally exists as a 5-member hemiketal ring (a furanose). This structure is responsible for the long metabolic pathway and high reactivity compared to glucose.
## Isomerism
D-Fructose has the same configuration at its penultimate carbon as D-glyceraldehyde. Fructose is sweeter than glucose because of its structure.
# Metabolism
Shown below is a diagram depicting the fructose metabolism.
# Health effects
Fructose absorption occurs via the GLUT-5[1] (fructose only) transporter, and the GLUT2 transporter, for which it competes with glucose and galactose. A deficiency of GLUT 5 may result in excess fructose carried into the lower intestine. There, it can provide nutrients for the existing gut flora, which produce gas. It may also cause water retention in the intestine. These effects may lead to bloating, excessive flatulence, loose stools, and even diarrhea depending on the amounts eaten and other factors.
Excess fructose consumption has been hypothesized to possibly cause insulin resistance, obesity,[2] elevated LDL cholesterol and triglycerides, leading to metabolic syndrome. However, unlike animal experiments, some human experiments have failed to show a correlation between fructose consumption and obesity. Short term tests, lack of dietary control, and lack of a non-fructose consuming control group are all confounding factors in human experiments. However, there are now a number of reports showing correlation of fructose consumption to obesity,[3][4] especially central obesity which is generally regarded as the most dangerous type.
There is a concern with Diabetic 1 patients and the apparent low GI of fructose. Fructose gives as high blood sugar spike as that obtained with glucose. In fact, GI only applies to high starch foods. The basic GI definition is chemically incorrect. This is because the body blood glucose response is "standardized" with 50g of glucose, while the GI Researchers use 50g of digestible carbohydrate as a reference quantity. Although all simple sugars are isomers, each have separate chemical properties.
This is illustrated with pure fructose. In a study from The American Journal of Clinical Nutrition, "fructose given alone increased the blood glucose almost as much as a similar amount of glucose (78% of the glucose-alone area)".[5][6][7][8][9]
A study in mice suggests that fructose increases obesity.[10]
One study concluded that fructose "produced significantly higher fasting plasma triacylglycerol values than did the glucose diet in men" and "if plasma triacylglycerols are a risk factor for cardiovascular disease, then diets high in fructose may be undesirable".[11] Bantle et al. "noted the same effects in a study of 14 healthy volunteers who sequentially ate a high-fructose diet and one almost devoid of the sugar."[12]
Studies that have compared high fructose corn syrup (an ingredient in soft drinks sold in the US) to sucrose (common cane sugar) find that they have essentially identical physiological effects. For instance, Melanson et al (2006), studied the effects of HFCS and sucrose sweetened drinks on blood glucose, insulin, leptin, and ghrelin levels. They found no significant differences in any of these parameters.[13] This is not surprising since sucrose is a disaccharide which digests to 50% glucose and 50% fructose; while the high fructose corn syrup most commonly used on soft drinks is 55% fructose.
Fructose also chelates minerals in the blood. This effect is especially important with micronutrients such as copper, chromium and zinc. Since these solutes are normally present in small quantities, chelation of small numbers of ions may lead to deficiency diseases, immune system impairment and even insulin resistance, a component of type II diabetes.[14]
Fructose is often recommended for diabetics due to its glycemic index being significantly lower than both glucose, sucrose and starches.
"The medical profession thinks fructose is better for diabetics than sugar," says Meira Field, Ph.D., a research chemist at the USDA, "but every cell in the body can metabolize glucose. However, all fructose must be metabolized in the liver. The livers of the rats on the high fructose diet looked like the livers of alcoholics, plugged with fat and cirrhotic."[15] This is not entirely true as certain other tissues do use fructose directly, notably the cells of the intestine, and sperm cells (for which fructose is the main energy source).
Fructose is a reducing sugar, as are all monosaccharides. The spontaneous addition of single sugar molecules to proteins, known as glycation, is a significant cause of damage in diabetics. Fructose appears to be as dangerous as glucose in this regard and so does not seem to be a better answer for diabetes for this reason alone.[16] This may be an important contribution to senescence and many age-related chronic diseases.[17]
Fructose is used as a substitute for sucrose (composed of one unit each of fructose and glucose linked together with a relatively weak glycosidic bond) because it is less expensive and has little effect on measured blood glucose levels. Often, fructose is consumed as high fructose corn syrup, which is corn syrup (glucose) that has been enzymatically treated by the enzyme glucose isomerase. This enzyme converts a portion of the glucose into fructose thus making it sweeter. This is done to such a degree as to yield corn syrup with an equivalent sweetness to sucrose by weight. While most carbohydrates have around the same amount of calories, fructose is sweeter and manufacturers can use less of it to get the same result.
The free fructose present in fruits, their juice, and honey is responsible for the greater sweetness of these natural sugar sources.
Unlike glucose, fructose is almost entirely metabolized in the liver. When fructose reaches the liver, says Dr. William J. Whelan, a biochemist at the University of Miami School of Medicine, "the liver goes bananas and stops everything else to metabolize the fructose." Eating fructose as compared to glucose results in lower circulating insulin levels, leptin, and ghrelin levels postprandially.[18] These hormones are implicated in the control of appetite and satiety, and it is hypothesized that eating lots of fructose could increase the likelihood of weight gain.[19] | https://www.wikidoc.org/index.php/D-fructose | |
d3bae38e26a45b769671051aab56c6319b0ba0c3 | wikidoc | Podiatry | Podiatry
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# Overview
Podiatry, podiatric medicine or chiropody is a field of healthcare devoted to the study and treatment of disorders of the foot, ankle, and the knee, leg and hip (collectively known as the lower extremity). The range of disorders podiatry can address largely depends on the scope of practice laid down in national, state, and/or provincial jurisdiction. It is practiced by podiatrists (Template:PronEng), chiropodists (Template:PronEng) and podiatric surgeons.
# History
The professional care of feet was in existence in ancient Egypt as evidenced by bas-relief carvings at the entrance to Ankmahor's tomb where work on hands and feet is depicted. Many Egyptologists believe tending feet probably spanned the whole of Egyptian civilization. The placement of carvings at the entrance of a tomb typically signified the profession of the buried individual and The Tomb of the Physician dates from 2400 BC.
Corns and calluses were described by Hippocrates who recognised the need to physically reduce hard skin, followed by removal of the cause. He invented skin scrapers for this purpose and these were the original scalpels. Aulus Cornelius Celsus, a Roman scientist and philosopher, was probably responsible for giving corns their name. Later Paul of Aegina (AD 615-690) defined a corn as "a white circular body like the head of a nail, forming in all parts of the body, but more especially on the soles of the feet and the toes. It may be removed in the course of some time by paring away the prominent part of it constantly with a scalpel or rubbing it down with pumice. The same thing can be done with a callus."
Until the turn of the 20th century, chiropodists - now known as podiatrists - were separate from organized medicine. They were independently licensed physicians who treated the feet, ankle and related leg structures. Lewis Durlacher was one of the first people to recognize the need for a protected profession. He tried to establish the first association of practitioners in 1854, although it would take another century to come to pass.
There are records of the King of France employing a personal podiatrist, as did Napoleon. In the United States, President Abraham Lincoln suffered greatly with his feet and chose a chiropodist named Isachar Zacharie, who not only cared for the president’s feet, but also was sent by President Lincoln on confidential missions to confer with leaders of the Confederacy during the U.S. Civil War.
The first society of chiropodists was established in New York in 1895 with the first school opening in 1911. One year later the British established a society at the London Foot Hospital and a school was added in 1919. In Australia professional associations appeared from 1924 onwards. The first American journal appeared in 1907, followed in 1912 by a UK journal. In 1939, the Australians introduced a training centre as well as a professional journal. The number of chiropodists increased markedly after the Great War then again after World War II. Increased numbers of ex-soldiers needing to be gainfully employed gave chiropody a boost and led to the need for registration in all English speaking countries. The study of the foot (i.e. podology), brought greater knowledge to the practice of foot care or podiatry.
# Podiatrist
A podiatrist (Template:PronEng, "poh-DYE-eh-trist") or foot doctor is a podiatric professional, a person devoted to the study and medical treatment of disorders of the foot, ankle and lower extremity. The term originated in the United States but has now become the accepted term in the English speaking world for all graduates of podiatric medical schools who have earned one of the following degrees: (D.P.M., D.P., B.Pod., Pod.B, or Pod.D.).
In other countries, such as the United Kingdom, Germany, New Zealand, and certain provinces of Canada, the title “chiropodist” (Template:PronEng) is often used. The titles “podiatrist” and “chiropodist”, in these countries, are now interchangeable, with the term “podiatrist” becoming more favoured within the profession. In the UK, individuals may not use the title “podiatrist” or “chiropodist” unless they are registrants of the Health Professions Council (HPC). They are protected titles and their use by non-registrants is unlawful. Such registration is normally only granted to those holding a specialised Bachelors degree or Diploma in Podiatry from one of the 13 recognised schools of podiatry in the UK. In these countries they usually only treat the foot through non-invasive procedures, they can however perform minor surgical procedures such as nail surgery using local anaesthetics. The United States is one of the few countries that grants more invasive surgical privileges to podiatrists.
Though the title "chiropodist" was previously used in the United States to designate what is now known as a "podiatrist," the title "chiropodist" is now considered to be an antiquated and etymologically incorrect term.
# Australia
In Australia, Podiatry is classified as an allied health profession, and is practised by individuals licensed by their represpective State Boards of Podiatry. There are seven registration boards and six teaching centres, with two levels of awards — unclassified bachelors degree and honours level. In Australia there exists 2 levels of professional accreditation and professional privilege; Podiatrist and Podiatric Surgeon (Surgical Podiatrist in the state of Queensland). Australian podiatrists are be able to practice abroad with their qualifications recognised in some Commonwealth countries.
## Education and Training
Australian Podiatrists complete an undergraduate degree ranging from 3 to 4 years of education. The first 2 years of this program are generally focused on various biomedical science subjects including anatomy, medical chemistry, biochemistry, physiology and patient psychology, similar to the medical curriculum. The following two years will then be spent focusing on podiatry specific areas such as podiatric biomechanics and human gait, podiatric orthopaedics or the non-surgical management of foot abnormalities, basic pharmacology, general medicine, general pathology, local and general anaesthesia, and surgical techniques such as Partial Nail Avulsion.
Australian Podiatric Surgeons are specialist podiatrists with further training in basic medicine, basic pharmacology, and training in foot surgery. They first complete a degree of 4 years, 2 years of clinical experience. Following this, a masters degree must be completed with focus on biomechanics, medicine, surgery, general surgery, advanced pharmacology, advanced medical imaging and clinical pathology. They then qualify for the status of Registrar with the Australasian College of Podiatric Surgeons. Following surgical training with a podiatric surgeon (3-5 years), and passing oral and written exams, Registrars may qualify for Fellowship status.
## Prescribing Rights
There is considerable variation between state laws regarding the prescribing rights of Australian Podiatrists. While all are able to utilize local anaesthesia for minor surgical techniques, some states allow suitable qualified podiatrists further privileges. Recent legislative changes, which are expected to come into effect soon, will allow Victorian graduates to prescribe relevant schedule 4 poisons. In other states such as Western Australia and South Australia, podiatrists with Masters Degree's in Podiatry, and extensive training in pharmacology are authorised to prescribe S4 poisons. States such as Queensland and New South Wales only grant prescribing privilege to those who are fellows of the Australasian College of Podiatric Surgeons, and thus are Podiatric Surgeons.
# Canada
In some parts of Canada the situation is legislatively stratified between the U.S. and British systems. For instance, in some provinces like British Columbia and Alberta, the standards is the same Doctor of Podiatric Medicine (D.P.M.) level as in the United States. Quebec, too, has recently changed to the D.P.M. level of training. Also in Quebec, in 2004, Université du Québec de Trois-Rivières started the first program of Podiatric Medicine in Canada. In the prairie provinces, the standard has been based on the British model of chiropody. Recognising this fact, in the province of Ontario, chiropodists and podiatrists are legislatively distinct occupational designations. Ontario chiropodists have a narrower scope of permitted practice than Ontario podiatrists (i.e., limitations on surgical practice). Both occupations are governed by the College of Chiropodists of Ontario. Persons licensed after July 1993 in Ontario can only be licensed as a chiropodist and cannot be licensed as a podiatrist, regardless of their training.
# New Zealand
Chiropody became a registered profession in New Zealand in 1969 with the requirement that all applicants take a recognized three-year course of training. Soon after the professional title was changed from Chiropody to Podiatry and The New Zealand School of Podiatry was established in 1970 at Petone under the direction of John Gallocher. Later the school moved to the Central Institute of Technology, Upper Hutt, Wellington. In 1976 the profession gained the legal right to use a local anaesthetic and began to introduce minor surgical ingrown toenail procedures as part of the scope of practice.
New Zealand podiatrists were granted the right of direct referral to radiologists for X-rays in 1984. Acknowledgement of podiatric expertise marked improved services to patients and eventually in 1989 suitably trained podiatrists were able to become licensed to take X-rays within their own practice. Diagnostic radiographic training is incorporated into the degree syllabus and on successful completion of the course, graduates register with the New Zealand National Radiation Laboratory.
In 1986 the profession undertook a needs analysis in conjunction with the Central Institute of Technology to identify competencies for podiatry in 2000. A Bachelor of Health Science was introduced in 1993.
# United Kingdom
A podiatrist is a specialist who studies foot pathology from a structural and functional standpoint, and who treats medical problems dealing with the foot.
Scope of practice:
- High risk patient management
- Sports injuries and biomechanics
- Foot and nail surgery
- Foot health education
- Foot surgery: congential and acquired deformities e.g flat foot, tarsal coalitions, bunion (hallux abducto valgus), digital deformity, ankle instability
In the UK any practitioner working under the reserved title Podiatrist must be registered with the Health Professions Council.
The Society of Chiropodists and Podiatrists is the largest professional body and trade union for registered chiropodists and students. The Society represents over 11,000 members working in private practice, the NHS, education, and the retail sector.
The Alliance of Private Sector Chiropody and Podiatry Practitioners represents both Podiatrists and Foot Health Practitioners who can be consulted directly by the public for early attention.
The profession of podiatry has developed from its origins in chiropody to become a medical speciality dealing with assessment, diagnosis and treatment of the lower limb.
# United States
In the United States, podiatric medicine and surgery is practiced by a licensed Doctor of Podiatric Medicine (D.P.M.). Education consists of a second entry degree which is a four-year program followed by a two- or three-year residency. Similar to Medical School, this training follows their four-year undergraduate college degree. The first four years of podiatric medical school are similar to training that traditional physicians (either medical doctors or osteopathic doctors) receive, but with more emphasis on foot, ankle and lower extremity problems and less emphasis on other topics such as embryology and pediatrics. Some of the podiatric medical schools are integrating into MD and DO schools for the first year or two. Being classified as a second entry degree, in order to be considered for admission an applicant must first complete a minimum of 90 semester hours at the university level and/or complete a bachelor's degree. The D.P.M. degree itself takes a minimum of four years to complete. Dentists likewise, have a separate educational school system. Thus there are five medical professions that allow for independent diagnosis and medical and surgical treatment: M.D., D.O., D.P.M., OD, and DDS/DMD.
The four-year podiatric medical school is followed by a residency, which is the hands-on post-doctoral training. There are two standard residencies named Podiatric Medicine and Surgery 24 or 36 (PM&S 24 or PM&S 36). These represent the two- or three-year residency training. Podiatric residents rotate through all main areas of medicine such as: emergency, pediatric, internal medicine, orthopedic and general surgery and of course podiatry — both clinic and surgical. During these rotations, attending physicians train the resident physicians in medicine and surgery. The surgical training varies from forefoot surgery to more complex foot, ankle, and leg reconstruction and salvage as well as trauma.
Podiatrists may independently diagnose, treat and prescribe medicine and perform surgery for disorders of the foot and in most states the ankle and leg. Board certification exists for podiatric physicians. Two speciality boards aligned with three areas of special practice are recognized by the Council on Podiatric Medical Education and the Joint Committee on the Recognition of Specialty Boards. Recognition is based on a board demonstrating that it can meet criteria established by the podiatric medical profession. The specialty board that certifies in the specialty areas of primary podiatric medicine and podiatric orthopedics is the American Board of Podiatric Orthopedics and Primary Podiatric Medicine. The specialty board that certifies in the specialty area of podiatric surgery is the American Board of Podiatric Surgery. The surgical board certification is divided into foot surgery and rearfoot/ankle reconstruction surgery. The rearfoot and ankle board certification requires at least a three-year residency to qualify. The surgical board which certifies minimally invasive percutaneous surgery is the American Board of Foot and Ankle Surgery. All of the surgical board certifications require applicants to submit their surgical cases to the board committee. The applicants then take written and oral exams prior to becoming board certified.
In the United States, the previous titles used for the Doctor of Podiatric Medicine (D.P.M.) degree were Doctor of Surgical Chiropody (D.S.C.) and Doctor of Podiatry (Pod.D.) Podiatry in the US currently encompasses a broader spectrum of medical practice than it used to. Podiatrists can now perform medical and surgical procedures in all 50 states, though the specific scope of practice does vary slightly in each state.
## Early educational developments
William Mathias Scholl began his career in Chicago, 1899, in a small shoe store specializing in comfort and specialist footwear. His concern for customers with painful foot conditions motivated him to enroll in medical school to study the anatomy and physiology of the foot.
By 1904 he had graduated from the Illinois Medical College as a doctor of medicine (M.D.) and launched his first foot care product, an arch support — The Foot-eazer. Dr. Scholl made it his life-long mission to improve the health, comfort and well-being of people through their feet.
In 1907 the Scholl Manufacturing Co. Inc. was created and in 1912 Dr. Scholl founded the Illinois College of Chiropody and Orthopaedics. By 1913, the company was expanding worldwide and
Dr. Scholl's first Foot Comfort Service shop opened in London. By the 1930s the company expanded its range for the comfort of the legs and began to make a range of compression hosiery for the relief of swollen ankles and varicose veins. Dr. Scholl was a prolific inventor and went on to create a range of remedy and cushioning devices covering the whole spectrum of common foot conditions.
In 1959 the first Scholl Exercise Sandal was created and became an international fashion hit and an icon for the brand.
Dr. Scholl's is a brand of foot-care products manufactured by Schering-Plough and footwear made by Brown Shoe Company. William M. Scholl died in 1968 at the age of 86, leaving the company to his nephew, William H. Scholl. The company had an initial public offering in 1971.
Just prior to Scholl founding a Chiropody College in Illinois, other innovators and individuals around the United States were founding other institutions of learning for foot care. Among these was M.J. Lewi, M.D. who founded what is now the oldest and largest college of podiatric medicine located in New York City. His institution later became the M.J. Lewi School of Podiatric Medicine and ultimately became the New York College of Podiatric Medicine.
The New York College of Podiatric Medicine notes that by 1911 the New York School of Chiropody had been created, dedicated to educating and training chiropodists. Dr. Maurice J. Lewi, a physician and educator, then serving as Secretary to the New York State Board of Examiners, was named the first president of the school.
Dr. Lewi assisted in developing the first legislation governing the practice of chiropody. He also developed the curricula and training programs for the first course of study at the school.
He was the first to suggest that the term "chiropody" be changed to "podiatry", since the term "chiropody" was etymologically incorrect. Some years later, the term "podiatry" was adopted by all other colleges of podiatric medicine and by the National Association of Chiropodists (NAC), now known as the American Podiatric Medical Association.
## Practice characteristics
While the majority of podiatric physicians are in solo practice, there has been a movement toward larger group practices as well as the use of podiatrists in multi-specialty groups including orthopedic groups, treating diabetes or in multi-specialty orthopedic surgical groups. Some podiatrists work within clinic practices such as the Indian Health System (IHS), the Rural Health Centers (RHC) and Community Health Center (FQHC) systems established by the Federal government to provide services to under insured and non-insured patients as well as within the United States Department of Veterans Affairs providing care to veterans of military service.
### Scope of practice
The differences in podiatric medical and surgical practice are determined by state law. Podiatrists are often defined as physicians in most States. Each state allows or limits the practice of podiatric medicine to the foot, ankle, and in many States, portions of the leg or related leg structures.
This may include surgery above the ankle and leg in 44 states. Most states require completion of a residency or a post-graduate training to practice. Most podiatric surgeons work in surgery centers or hospitals performing both medical and surgical treatments for patients. As in many other specialties, some podiatrists work in nursing homes and some perform house calls for patients. Podiatric patients range from newborns and infants to the geriatric.
### Medical and orthopedic practice
Some podiatrists limit their practices to the non-(hospital) surgical treatment of patients. Because much work in podiatric medicine and surgery involves cutting of some kind, many procedures are considered surgical by insurance companies including tasks such as the cutting of nails, removing of corns or callus, which the general public would not ordinarily consider to be surgery. These podiatrists use their skills in handling arthritic, diabetic, and other medical problems associated with the feet and lower extremities. Some use devices fitted in shoes (orthotics) or modify the shoe itself to make walking better or easier. Some practices focus on sports medicine and treat many runners, dancers, soccer players, and other athletes.
### Surgical practice
Within the scope of practice, podiatrists are the experts at foot, ankle & related leg structures surgery. Some podiatrists have primarily surgical practices. Some specialists complete additional fellowship training in reconstruction of the foot, ankle and leg. Many podiatric surgeons specialize in minimally invasive percutaneous surgery. Most podiatrists utilize medical, orthopedic, biomechanical and surgical practices. Indeed, surgical podiatric principles rest on a base of orthopedic and kinesthetic knowledge.
## Distinction from Orthopedic Foot and Ankle Surgery
Orthopaedic foot and ankle specialistis first must complete a medical degree either (MD, MBBS, MBChB, etc) or Osteopathic D.O. degree. After completion of medical school orthopaedic surgeons complete a 5-6 year residency program. A majority of orthopedic residency programs dedicated 12 week or less to foot and ankle surgery. To compensate for this, some orthopedic surgeons may complete a foot and ankle fellowship that varies from 3 - 12 months. This contrasts with podiatric surgeons who have a residency of 2 to 3 years dedicated to foot and ankle surgery. Some of the practice of orthopedic surgeons and podiatrists is overlapping. Foot and ankle orthopaedic surgeons often work in the same practices as podiatrists, and will occasionally refer patients to one another.
## Job opportunities and salary
The US Department of Labor, Bureau of Labor Statistics expects the need for podiatrists to rise, but slowly because podiatrists tend to have long careers before retirement. The most recent podiatric practice survey in 2006 revealed a median salary of $150,000 and in 2007, podiatric medicine placed 15th on the Forbes survey of “America’s 25 Best Paying Jobs.”
## Colleges and education
There are eight colleges of podiatric medicine in the United States with a ninth school being added in 2009 at Western University of Health Sciences. These are governed by the American Association of Colleges of Podiatric Medicine (AACPM). The AACPM describes its mission as to enhance academic podiatric medicine.
# Speciality branches
Podiatrists worldwide, regardless of educational pathways, treat a wide variety of foot and lower extremity conditions, through conservative or surgical approaches.
Amongst those subspecialties are such fields of practice as:
- General Podiatry Practice
- Podopaediatrics (the study of children's foot and ankle conditions)
- Sports Medicine
- Diabetic foot and wound care
- Forensic Podiatry (the study of footprints, footwear, shoeprints and feet associated with crime scene investigations)
- Rheumatology
- Gerontology
- Reconstructive foot and ankle surgery
- Minimally invasive percutaneous surgery
# Professional societies and organizations
- Alpha Gamma Kappa
- Kappa Tau Epsilon
- Pi Delta National Honor Society
- Student National Podiatric Medical Association (SNPMA)
- American Podiatric Medical Students' Association (APMSA) | Podiatry
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# Overview
Podiatry, podiatric medicine or chiropody is a field of healthcare devoted to the study and treatment of disorders of the foot, ankle, and the knee, leg and hip (collectively known as the lower extremity). The range of disorders podiatry can address largely depends on the scope of practice laid down in national, state, and/or provincial jurisdiction. It is practiced by podiatrists (Template:PronEng), chiropodists (Template:PronEng) and podiatric surgeons.
# History
The professional care of feet was in existence in ancient Egypt as evidenced by bas-relief carvings at the entrance to Ankmahor's tomb where work on hands and feet is depicted. Many Egyptologists believe tending feet probably spanned the whole of Egyptian civilization. The placement of carvings at the entrance of a tomb typically signified the profession of the buried individual and The Tomb of the Physician dates from 2400 BC.
Corns and calluses were described by Hippocrates who recognised the need to physically reduce hard skin, followed by removal of the cause. He invented skin scrapers for this purpose and these were the original scalpels. Aulus Cornelius Celsus, a Roman scientist and philosopher, was probably responsible for giving corns their name. Later Paul of Aegina (AD 615-690) defined a corn as "a white circular body like the head of a nail, forming in all parts of the body, but more especially on the soles of the feet and the toes. It may be removed in the course of some time by paring away the prominent part of it constantly with a scalpel or rubbing it down with pumice. The same thing can be done with a callus."
Until the turn of the 20th century, chiropodists - now known as podiatrists - were separate from organized medicine. They were independently licensed physicians who treated the feet, ankle and related leg structures. Lewis Durlacher was one of the first people to recognize the need for a protected profession. He tried to establish the first association of practitioners in 1854, although it would take another century to come to pass.
There are records of the King of France employing a personal podiatrist, as did Napoleon. In the United States, President Abraham Lincoln suffered greatly with his feet and chose a chiropodist named Isachar Zacharie, who not only cared for the president’s feet, but also was sent by President Lincoln on confidential missions to confer with leaders of the Confederacy during the U.S. Civil War.
The first society of chiropodists was established in New York in 1895 with the first school opening in 1911. One year later the British established a society at the London Foot Hospital and a school was added in 1919. In Australia professional associations appeared from 1924 onwards. The first American journal appeared in 1907, followed in 1912 by a UK journal. In 1939, the Australians introduced a training centre as well as a professional journal. The number of chiropodists increased markedly after the Great War then again after World War II. Increased numbers of ex-soldiers needing to be gainfully employed gave chiropody a boost and led to the need for registration in all English speaking countries. The study of the foot (i.e. podology), brought greater knowledge to the practice of foot care or podiatry.
# Podiatrist
A podiatrist (Template:PronEng, "poh-DYE-eh-trist") or foot doctor is a podiatric professional, a person devoted to the study and medical treatment of disorders of the foot, ankle and lower extremity. The term originated in the United States but has now become the accepted term in the English speaking world for all graduates of podiatric medical schools who have earned one of the following degrees: (D.P.M., D.P., B.Pod., Pod.B, or Pod.D.).
In other countries, such as the United Kingdom, Germany, New Zealand, and certain provinces of Canada, the title “chiropodist” (Template:PronEng) is often used. The titles “podiatrist” and “chiropodist”, in these countries, are now interchangeable, with the term “podiatrist” becoming more favoured within the profession. In the UK, individuals may not use the title “podiatrist” or “chiropodist” unless they are registrants of the Health Professions Council (HPC). They are protected titles and their use by non-registrants is unlawful. Such registration is normally only granted to those holding a specialised Bachelors degree or Diploma in Podiatry from one of the 13 recognised schools of podiatry in the UK. In these countries they usually only treat the foot through non-invasive procedures, they can however perform minor surgical procedures such as nail surgery using local anaesthetics. The United States is one of the few countries that grants more invasive surgical privileges to podiatrists.[1] [2]
Though the title "chiropodist" was previously used in the United States to designate what is now known as a "podiatrist," the title "chiropodist" is now considered to be an antiquated and etymologically incorrect term.
# Australia
In Australia, Podiatry is classified as an allied health profession, and is practised by individuals licensed by their represpective State Boards of Podiatry. There are seven registration boards and six teaching centres, with two levels of awards — unclassified bachelors degree and honours level. In Australia there exists 2 levels of professional accreditation and professional privilege; Podiatrist and Podiatric Surgeon (Surgical Podiatrist in the state of Queensland). Australian podiatrists are be able to practice abroad with their qualifications recognised in some Commonwealth countries.
## Education and Training
Australian Podiatrists complete an undergraduate degree ranging from 3 to 4 years of education. The first 2 years of this program are generally focused on various biomedical science subjects including anatomy, medical chemistry, biochemistry, physiology and patient psychology, similar to the medical curriculum. The following two years will then be spent focusing on podiatry specific areas such as podiatric biomechanics and human gait, podiatric orthopaedics or the non-surgical management of foot abnormalities, basic pharmacology, general medicine, general pathology, local and general anaesthesia, and surgical techniques such as Partial Nail Avulsion.
Australian Podiatric Surgeons are specialist podiatrists with further training in basic medicine, basic pharmacology, and training in foot surgery. They first complete a degree of 4 years, 2 years of clinical experience. Following this, a masters degree must be completed with focus on biomechanics, medicine, surgery, general surgery, advanced pharmacology, advanced medical imaging and clinical pathology. They then qualify for the status of Registrar with the Australasian College of Podiatric Surgeons. Following surgical training with a podiatric surgeon (3-5 years), and passing oral and written exams, Registrars may qualify for Fellowship status.
## Prescribing Rights
There is considerable variation between state laws regarding the prescribing rights of Australian Podiatrists. While all are able to utilize local anaesthesia for minor surgical techniques, some states allow suitable qualified podiatrists further privileges. Recent legislative changes, which are expected to come into effect soon, will allow Victorian graduates to prescribe relevant schedule 4 poisons. In other states such as Western Australia and South Australia, podiatrists with Masters Degree's in Podiatry, and extensive training in pharmacology are authorised to prescribe S4 poisons. States such as Queensland and New South Wales only grant prescribing privilege to those who are fellows of the Australasian College of Podiatric Surgeons, and thus are Podiatric Surgeons.
# Canada
In some parts of Canada the situation is legislatively stratified between the U.S. and British systems. For instance, in some provinces like British Columbia and Alberta, the standards is the same Doctor of Podiatric Medicine (D.P.M.) level as in the United States. Quebec, too, has recently changed to the D.P.M. level of training. Also in Quebec, in 2004, Université du Québec de Trois-Rivières started the first program of Podiatric Medicine in Canada. In the prairie provinces, the standard has been based on the British model of chiropody. Recognising this fact, in the province of Ontario, chiropodists and podiatrists are legislatively distinct occupational designations. Ontario chiropodists have a narrower scope of permitted practice than Ontario podiatrists (i.e., limitations on surgical practice). Both occupations are governed by the College of Chiropodists of Ontario. Persons licensed after July 1993 in Ontario can only be licensed as a chiropodist and cannot be licensed as a podiatrist, regardless of their training.
# New Zealand
Chiropody became a registered profession in New Zealand in 1969 with the requirement that all applicants take a recognized three-year course of training. Soon after the professional title was changed from Chiropody to Podiatry and The New Zealand School of Podiatry was established in 1970 at Petone under the direction of John Gallocher. Later the school moved to the Central Institute of Technology, Upper Hutt, Wellington. In 1976 the profession gained the legal right to use a local anaesthetic and began to introduce minor surgical ingrown toenail procedures as part of the scope of practice.
New Zealand podiatrists were granted the right of direct referral to radiologists for X-rays in 1984. Acknowledgement of podiatric expertise marked improved services to patients and eventually in 1989 suitably trained podiatrists were able to become licensed to take X-rays within their own practice. Diagnostic radiographic training is incorporated into the degree syllabus and on successful completion of the course, graduates register with the New Zealand National Radiation Laboratory.
In 1986 the profession undertook a needs analysis in conjunction with the Central Institute of Technology to identify competencies for podiatry in 2000. A Bachelor of Health Science was introduced in 1993.
# United Kingdom
A podiatrist is a specialist who studies foot pathology from a structural and functional standpoint, and who treats medical problems dealing with the foot.[3]
Scope of practice:
- High risk patient management
- Sports injuries and biomechanics
- Foot and nail surgery
- Foot health education
- Foot surgery: congential and acquired deformities e.g flat foot, tarsal coalitions, bunion (hallux abducto valgus), digital deformity, ankle instability
In the UK any practitioner working under the reserved title Podiatrist must be registered with the Health Professions Council.
The Society of Chiropodists and Podiatrists is the largest professional body and trade union for registered chiropodists and students. The Society represents over 11,000 members working in private practice, the NHS, education, and the retail sector.
The Alliance of Private Sector Chiropody and Podiatry Practitioners represents both Podiatrists and Foot Health Practitioners who can be consulted directly by the public for early attention.
The profession of podiatry has developed from its origins in chiropody to become a medical speciality dealing with assessment, diagnosis and treatment of the lower limb.[4]
# United States
In the United States, podiatric medicine and surgery is practiced by a licensed Doctor of Podiatric Medicine (D.P.M.). Education consists of a second entry degree which is a four-year program followed by a two- or three-year residency. Similar to Medical School, this training follows their four-year undergraduate college degree. The first four years of podiatric medical school are similar to training that traditional physicians (either medical doctors or osteopathic doctors) receive, but with more emphasis on foot, ankle and lower extremity problems and less emphasis on other topics such as embryology and pediatrics. Some of the podiatric medical schools are integrating into MD and DO schools for the first year or two. Being classified as a second entry degree, in order to be considered for admission an applicant must first complete a minimum of 90 semester hours at the university level and/or complete a bachelor's degree. The D.P.M. degree itself takes a minimum of four years to complete. Dentists likewise, have a separate educational school system. Thus there are five medical professions that allow for independent diagnosis and medical and surgical treatment: M.D., D.O., D.P.M., OD, and DDS/DMD.
The four-year podiatric medical school is followed by a residency, which is the hands-on post-doctoral training. There are two standard residencies named Podiatric Medicine and Surgery 24 or 36 (PM&S 24 or PM&S 36). These represent the two- or three-year residency training. Podiatric residents rotate through all main areas of medicine such as: emergency, pediatric, internal medicine, orthopedic and general surgery and of course podiatry — both clinic and surgical. During these rotations, attending physicians train the resident physicians in medicine and surgery. The surgical training varies from forefoot surgery to more complex foot, ankle, and leg reconstruction and salvage as well as trauma.
Podiatrists may independently diagnose, treat and prescribe medicine and perform surgery for disorders of the foot and in most states the ankle and leg. Board certification exists for podiatric physicians. Two speciality boards aligned with three areas of special practice are recognized by the Council on Podiatric Medical Education and the Joint Committee on the Recognition of Specialty Boards. Recognition is based on a board demonstrating that it can meet criteria established by the podiatric medical profession. The specialty board that certifies in the specialty areas of primary podiatric medicine and podiatric orthopedics is the American Board of Podiatric Orthopedics and Primary Podiatric Medicine. The specialty board that certifies in the specialty area of podiatric surgery is the American Board of Podiatric Surgery. The surgical board certification is divided into foot surgery and rearfoot/ankle reconstruction surgery. The rearfoot and ankle board certification requires at least a three-year residency to qualify. The surgical board which certifies minimally invasive percutaneous surgery is the American Board of Foot and Ankle Surgery. All of the surgical board certifications require applicants to submit their surgical cases to the board committee. The applicants then take written and oral exams prior to becoming board certified.
In the United States, the previous titles used for the Doctor of Podiatric Medicine (D.P.M.) degree were Doctor of Surgical Chiropody (D.S.C.) and Doctor of Podiatry (Pod.D.) Podiatry in the US currently encompasses a broader spectrum of medical practice than it used to. Podiatrists can now perform medical and surgical procedures in all 50 states, though the specific scope of practice does vary slightly in each state.
## Early educational developments
William Mathias Scholl began his career in Chicago, 1899, in a small shoe store specializing in comfort and specialist footwear. His concern for customers with painful foot conditions motivated him to enroll in medical school to study the anatomy and physiology of the foot.
By 1904 he had graduated from the Illinois Medical College as a doctor of medicine (M.D.) and launched his first foot care product, an arch support — The Foot-eazer. Dr. Scholl made it his life-long mission to improve the health, comfort and well-being of people through their feet.
In 1907 the Scholl Manufacturing Co. Inc. was created and in 1912 Dr. Scholl founded the Illinois College of Chiropody and Orthopaedics. By 1913, the company was expanding worldwide and
Dr. Scholl's first Foot Comfort Service shop opened in London. By the 1930s the company expanded its range for the comfort of the legs and began to make a range of compression hosiery for the relief of swollen ankles and varicose veins. Dr. Scholl was a prolific inventor and went on to create a range of remedy and cushioning devices covering the whole spectrum of common foot conditions.
In 1959 the first Scholl Exercise Sandal was created and became an international fashion hit and an icon for the brand.
Dr. Scholl's is a brand of foot-care products manufactured by Schering-Plough and footwear made by Brown Shoe Company. William M. Scholl died in 1968 at the age of 86, leaving the company to his nephew, William H. Scholl. The company had an initial public offering in 1971.
Just prior to Scholl founding a Chiropody College in Illinois, other innovators and individuals around the United States were founding other institutions of learning for foot care. Among these was M.J. Lewi, M.D. who founded what is now the oldest and largest college of podiatric medicine located in New York City. His institution later became the M.J. Lewi School of Podiatric Medicine and ultimately became the New York College of Podiatric Medicine.
The New York College of Podiatric Medicine notes that by 1911 the New York School of Chiropody had been created, dedicated to educating and training chiropodists. Dr. Maurice J. Lewi, a physician and educator, then serving as Secretary to the New York State Board of Examiners, was named the first president of the school.
Dr. Lewi assisted in developing the first legislation governing the practice of chiropody. He also developed the curricula and training programs for the first course of study at the school.
He was the first to suggest that the term "chiropody" be changed to "podiatry", since the term "chiropody" was etymologically incorrect. Some years later, the term "podiatry" was adopted by all other colleges of podiatric medicine and by the National Association of Chiropodists (NAC), now known as the American Podiatric Medical Association.
## Practice characteristics
While the majority of podiatric physicians are in solo practice, there has been a movement toward larger group practices as well as the use of podiatrists in multi-specialty groups including orthopedic groups, treating diabetes or in multi-specialty orthopedic surgical groups. Some podiatrists work within clinic practices such as the Indian Health System (IHS), the Rural Health Centers (RHC) and Community Health Center (FQHC) systems established by the Federal government to provide services to under insured and non-insured patients as well as within the United States Department of Veterans Affairs providing care to veterans of military service.
### Scope of practice
The differences in podiatric medical and surgical practice are determined by state law. Podiatrists are often defined as physicians in most States. Each state allows or limits the practice of podiatric medicine to the foot, ankle, and in many States, portions of the leg or related leg structures.
This may include surgery above the ankle and leg in 44 states. Most states require completion of a residency or a post-graduate training to practice. Most podiatric surgeons work in surgery centers or hospitals performing both medical and surgical treatments for patients. As in many other specialties, some podiatrists work in nursing homes and some perform house calls for patients. Podiatric patients range from newborns and infants to the geriatric.
### Medical and orthopedic practice
Some podiatrists limit their practices to the non-(hospital) surgical treatment of patients. Because much work in podiatric medicine and surgery involves cutting of some kind, many procedures are considered surgical by insurance companies including tasks such as the cutting of nails, removing of corns or callus, which the general public would not ordinarily consider to be surgery. These podiatrists use their skills in handling arthritic, diabetic, and other medical problems associated with the feet and lower extremities. Some use devices fitted in shoes (orthotics) or modify the shoe itself to make walking better or easier. Some practices focus on sports medicine and treat many runners, dancers, soccer players, and other athletes.
### Surgical practice
Within the scope of practice, podiatrists are the experts at foot, ankle & related leg structures surgery. Some podiatrists have primarily surgical practices. Some specialists complete additional fellowship training in reconstruction of the foot, ankle and leg. Many podiatric surgeons specialize in minimally invasive percutaneous surgery. Most podiatrists utilize medical, orthopedic, biomechanical and surgical practices. Indeed, surgical podiatric principles rest on a base of orthopedic and kinesthetic knowledge.
## Distinction from Orthopedic Foot and Ankle Surgery
Orthopaedic foot and ankle specialistis first must complete a medical degree either (MD, MBBS, MBChB, etc) or Osteopathic D.O. degree. After completion of medical school orthopaedic surgeons complete a 5-6 year residency program. A majority of orthopedic residency programs dedicated 12 week or less to foot and ankle surgery.[5] To compensate for this, some orthopedic surgeons may complete a foot and ankle fellowship that varies from 3 - 12 months. This contrasts with podiatric surgeons who have a residency of 2 to 3 years dedicated to foot and ankle surgery. Some of the practice of orthopedic surgeons and podiatrists is overlapping. Foot and ankle orthopaedic surgeons often work in the same practices as podiatrists, and will occasionally refer patients to one another.
## Job opportunities and salary
The US Department of Labor, Bureau of Labor Statistics expects the need for podiatrists to rise, but slowly because podiatrists tend to have long careers before retirement. The most recent podiatric practice survey in 2006 revealed a median salary of $150,000 and in 2007, podiatric medicine placed 15th on the Forbes survey of “America’s 25 Best Paying Jobs.” [6]
## Colleges and education
There are eight colleges of podiatric medicine in the United States with a ninth school being added in 2009 at Western University of Health Sciences. These are governed by the American Association of Colleges of Podiatric Medicine (AACPM). The AACPM describes its mission as to enhance academic podiatric medicine.
# Speciality branches
Podiatrists worldwide, regardless of educational pathways, treat a wide variety of foot and lower extremity conditions, through conservative or surgical approaches.
Amongst those subspecialties are such fields of practice as:
- General Podiatry Practice
- Podopaediatrics (the study of children's foot and ankle conditions)
- Sports Medicine
- Diabetic foot and wound care
- Forensic Podiatry (the study of footprints, footwear, shoeprints and feet associated with crime scene investigations)
- Rheumatology
- Gerontology
- Reconstructive foot and ankle surgery
- Minimally invasive percutaneous surgery
# Professional societies and organizations
- Alpha Gamma Kappa
- Kappa Tau Epsilon
- Pi Delta National Honor Society
- Student National Podiatric Medical Association (SNPMA)
- American Podiatric Medical Students' Association (APMSA) | https://www.wikidoc.org/index.php/D.P.M. | |
a49ac7a2bcf3ae3d4cc313503eeedfb53f2c6f51 | wikidoc | DCA agar | DCA agar
DCA agar - Deoxycholate Citrate Agar - is particularly useful for the isolation of organisms that cause bacilliary dysentery, salmonella strains that cause food poisoning and Salmonella Paratyphi. It is not so selective for Salmonella Typhi. This growth medium is inhibitory to most gut bacteria, in particular species of the genus Proteus, although these species do survive on DCA agar. It is therefore essential that suspected pathogens must be subcultured on a less inhibitory medium prior to identification.
Salmonella spp appear to be yellow or colourless colonies, often with a dark centre.
As there are many bacteria that also look like Salmonella on DCA, it is widely recommended that more selective agars are used for the identification of Salmonella, namely xylose lysine deoxycholate (XLD) agar.
This growth medium is heat-sensitive and should be poured and cooled as soon as possible after addition of the deoxycholate, otherwise it tends to become very soft and difficult to handle. It has a pH of approximately 7.3, and when poured and cooled, appears light to dark pink in colour.
DCA agar contains: | DCA agar
DCA agar - Deoxycholate Citrate Agar - is particularly useful for the isolation of organisms that cause bacilliary dysentery, salmonella strains that cause food poisoning and Salmonella Paratyphi. It is not so selective for Salmonella Typhi. This growth medium is inhibitory to most gut bacteria, in particular species of the genus Proteus, although these species do survive on DCA agar. It is therefore essential that suspected pathogens must be subcultured on a less inhibitory medium prior to identification.
Salmonella spp appear to be yellow or colourless colonies, often with a dark centre.
As there are many bacteria that also look like Salmonella on DCA, it is widely recommended that more selective agars are used for the identification of Salmonella, namely xylose lysine deoxycholate (XLD) agar.
This growth medium is heat-sensitive and should be poured and cooled as soon as possible after addition of the deoxycholate, otherwise it tends to become very soft and difficult to handle. It has a pH of approximately 7.3, and when poured and cooled, appears light to dark pink in colour.
DCA agar contains:
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/DCA_agar | |
bad1fab197e527e396e9fe545b0ace52fa1f8bc4 | wikidoc | DEFB103A | DEFB103A
Beta-defensin 103 is a protein that in humans is encoded by the DEFB103A gene.
# Function
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 103B, which has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense.
In dogs, the product of the same genetic locus, β-Defensin 103, also plays a role in pigmentation, being an agonist of the melanocortin 1 receptor. | DEFB103A
Beta-defensin 103 is a protein that in humans is encoded by the DEFB103A gene.[1][2][3]
# Function
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 103B, which has broad spectrum antimicrobial activity and may play an important role in innate epithelial defense.[3]
In dogs, the product of the same genetic locus, β-Defensin 103, also plays a role in pigmentation, being an agonist of the melanocortin 1 receptor.[4] | https://www.wikidoc.org/index.php/DEFB103A | |
43b40d5a7fc8a13526f18c9410976bb5422333cc | wikidoc | DEFB106A | DEFB106A
Beta-defensin 106 is a protein that in humans is encoded by the DEFB106A gene.
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy.
# Function
The purified DEFB106 showed antimicrobial activity against Escherichia coli, Candida albicans and Staphylococcus aureus. | DEFB106A
Beta-defensin 106 is a protein that in humans is encoded by the DEFB106A gene.[1][2]
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy.[2]
# Function
The purified DEFB106 showed antimicrobial activity against Escherichia coli, Candida albicans and Staphylococcus aureus.[3] | https://www.wikidoc.org/index.php/DEFB106A | |
914d2801329aaf43efc042ca15b3f683d9d87ecc | wikidoc | DNA-PKcs | DNA-PKcs
DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. The DNA-Pkcs protein is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids.
# Function
DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase called DNA-PK. The second component is the autoimmune antigen Ku. On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity. DNA-PKcs is required for the non-homologous end joining (NHEJ) pathway of DNA repair, which rejoins double-strand breaks. It is also required for V(D)J recombination, a process that utilizes NHEJ to promote immune system diversity. DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect.
Many proteins have been identified as substrates for the kinase activity of DNA-PK. Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break. DNA-PK also cooperates with ATR and ATM to phosphorylate proteins involved in the DNA damage checkpoint.
# Cancer
DNA damage appears to be the primary underlying cause of cancer, and deficiencies in DNA repair genes likely underlie many forms of cancer. If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutations due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. Such mutations and epigenetic alterations may give rise to cancer.
PRKDC (DNA-PKcs) mutations were found in 3 out of 10 of endometriosis-associated ovarian cancers, as well as in the field defects from which they arose. They were also found in 10% of breast and pancreatic cancers.
Reductions in expression of DNA repair genes (usually caused by epigenetic alterations) are very common in cancers, and are ordinarily even more frequent than mutational defects in DNA repair genes in cancers. DNA-PKcs expression was reduced by 23% to 57% in six cancers as indicated in the table.
It is not clear what causes reduced expression of DNA-PKcs in cancers. MicroRNA-101 targets DNA-PKcs via binding to the 3'- UTR of DNA-PKcs mRNA and efficiently reduces protein levels of DNA-PKcs. But miR-101 is more often decreased in cancers, rather than increased.
HMGA2 protein could also have an effect on DNA-PKcs. HMGA2 delays the release of DNA-PKcs from sites of double-strand breaks, interfering with DNA repair by non-homologous end joining and causing chromosomal aberrations. The let-7a microRNA normally represses the HMGA2 gene. In normal adult tissues, almost no HMGA2 protein is present. In many cancers, let-7 microRNA is repressed. As an example, in breast cancers the promoter region controlling let-7a-3/let-7b microRNA is frequently repressed by hypermethylation. Epigenetic reduction or absence of let-7a microRNA allows high expression of the HMGA2 protein and this would lead to defective expression of DNA-PKcs.
DNA-PKcs can be up-regulated by stressful conditions such as in Helicobacter pylori-associated gastritis. After ionizing radiation DNA-PKcs was increased in the surviving cells of oral squamous cell carcinoma tissues.
The ATM protein is important in homologous recombinational repair (HRR) of DNA double strand breaks. When cancer cells are deficient in ATM the cells are "addicted" to DNA-PKcs, important in the alternative DNA repair pathway for double-strand breaks, non-homologous end joining (NHEJ). That is, in ATM-mutant cells, an inhibitor of DNA-PKcs causes high levels of apoptotic cell death. In ATM mutant cells, additional loss of DNA-PKcs leaves the cells without either major pathway (HRR and NHEJ) for repair of DNA double-strand breaks.
Elevated DNA-PKcs expression is found in a large fraction (40% to 90%) of some cancers (the remaining fraction of cancers often has reduced or absent expression of DNA-PKcs). The elevation of DNA-PKcs is thought to reflect the induction of a compensatory DNA repair capability, due to the genome instability in these cancers. (As indicated in the article Genome instability, such genome instability may be due to deficiencies in other DNA repair genes present in the cancers.) Elevated DNA-PKcs is thought to be "beneficial to the tumor cells", though it would be at the expense of the patient. As indicated in a table listing 12 types of cancer reported in 20 publications, the fraction of cancers with over-expression of DNA-PKcs is often associated with an advanced stage of the cancer and shorter survival time for the patient. However, the table also indicates that for some cancers, the fraction of cancers with reduced or absent DNA-PKcs is also associated with advanced stage and poor patient survival.
# Aging
Non-homologous end joining (NHEJ) is the principal DNA repair process used by mammalian somatic cells to cope with double-strand breaks that continually occur in the genome. DNA-PKcs is one of the key components of the NHEJ machinery. DNA-PKcs deficient mice have a shorter lifespan and show an earlier onset of numerous aging related pathologies than corresponding wild-type littermates. These findings suggest that failure to efficiently repair DNA double-strand breaks results in premature aging, consistent with the DNA damage theory of aging. (See also Bernstein et al.)
# Interactions
DNA-PKcs has been shown to interact with:
- ATM,
- C1D, and
- CDC5L,
- CHEK1,
- CHUK,
- CIB1,
- DCLRE1C,
- ILF2,
- ILF3,
- Ku80,
- NCOA6,
- P53,
- RPA2, and
- WRN. | DNA-PKcs
DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7.[1] DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. The DNA-Pkcs protein is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids.[2][3]
# Function
DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase called DNA-PK. The second component is the autoimmune antigen Ku. On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity.[4] DNA-PKcs is required for the non-homologous end joining (NHEJ) pathway of DNA repair, which rejoins double-strand breaks. It is also required for V(D)J recombination, a process that utilizes NHEJ to promote immune system diversity. DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect.
Many proteins have been identified as substrates for the kinase activity of DNA-PK. Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break.[5] DNA-PK also cooperates with ATR and ATM to phosphorylate proteins involved in the DNA damage checkpoint.
# Cancer
DNA damage appears to be the primary underlying cause of cancer,[6][7] and deficiencies in DNA repair genes likely underlie many forms of cancer.[8][9] If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutations due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair.[10][11] Such mutations and epigenetic alterations may give rise to cancer.
PRKDC (DNA-PKcs) mutations were found in 3 out of 10 of endometriosis-associated ovarian cancers, as well as in the field defects from which they arose.[12] They were also found in 10% of breast and pancreatic cancers.[13]
Reductions in expression of DNA repair genes (usually caused by epigenetic alterations) are very common in cancers, and are ordinarily even more frequent than mutational defects in DNA repair genes in cancers.[14] DNA-PKcs expression was reduced by 23% to 57% in six cancers as indicated in the table.
It is not clear what causes reduced expression of DNA-PKcs in cancers. MicroRNA-101 targets DNA-PKcs via binding to the 3'- UTR of DNA-PKcs mRNA and efficiently reduces protein levels of DNA-PKcs.[21] But miR-101 is more often decreased in cancers, rather than increased.[22][23]
HMGA2 protein could also have an effect on DNA-PKcs. HMGA2 delays the release of DNA-PKcs from sites of double-strand breaks, interfering with DNA repair by non-homologous end joining and causing chromosomal aberrations.[24] The let-7a microRNA normally represses the HMGA2 gene.[25][26] In normal adult tissues, almost no HMGA2 protein is present. In many cancers, let-7 microRNA is repressed. As an example, in breast cancers the promoter region controlling let-7a-3/let-7b microRNA is frequently repressed by hypermethylation.[27] Epigenetic reduction or absence of let-7a microRNA allows high expression of the HMGA2 protein and this would lead to defective expression of DNA-PKcs.
DNA-PKcs can be up-regulated by stressful conditions such as in Helicobacter pylori-associated gastritis.[28] After ionizing radiation DNA-PKcs was increased in the surviving cells of oral squamous cell carcinoma tissues.[29]
The ATM protein is important in homologous recombinational repair (HRR) of DNA double strand breaks. When cancer cells are deficient in ATM the cells are "addicted" to DNA-PKcs, important in the alternative DNA repair pathway for double-strand breaks, non-homologous end joining (NHEJ).[30] That is, in ATM-mutant cells, an inhibitor of DNA-PKcs causes high levels of apoptotic cell death. In ATM mutant cells, additional loss of DNA-PKcs leaves the cells without either major pathway (HRR and NHEJ) for repair of DNA double-strand breaks.
Elevated DNA-PKcs expression is found in a large fraction (40% to 90%) of some cancers (the remaining fraction of cancers often has reduced or absent expression of DNA-PKcs). The elevation of DNA-PKcs is thought to reflect the induction of a compensatory DNA repair capability, due to the genome instability in these cancers.[31] (As indicated in the article Genome instability, such genome instability may be due to deficiencies in other DNA repair genes present in the cancers.) Elevated DNA-PKcs is thought to be "beneficial to the tumor cells",[31] though it would be at the expense of the patient. As indicated in a table listing 12 types of cancer reported in 20 publications,[31] the fraction of cancers with over-expression of DNA-PKcs is often associated with an advanced stage of the cancer and shorter survival time for the patient. However, the table also indicates that for some cancers, the fraction of cancers with reduced or absent DNA-PKcs is also associated with advanced stage and poor patient survival.
# Aging
Non-homologous end joining (NHEJ) is the principal DNA repair process used by mammalian somatic cells to cope with double-strand breaks that continually occur in the genome. DNA-PKcs is one of the key components of the NHEJ machinery. DNA-PKcs deficient mice have a shorter lifespan and show an earlier onset of numerous aging related pathologies than corresponding wild-type littermates.[32][33] These findings suggest that failure to efficiently repair DNA double-strand breaks results in premature aging, consistent with the DNA damage theory of aging. (See also Bernstein et al.[34])
# Interactions
DNA-PKcs has been shown to interact with:
- ATM,[35][36]
- C1D,[37] and
- CDC5L,[38]
- CHEK1,[35][39]
- CHUK,[40]
- CIB1,[41]
- DCLRE1C,[42]
- ILF2,[43]
- ILF3,[43]
- Ku80,[44][45][46]
- NCOA6,[47]
- P53,[35][37][39]
- RPA2,[48] and
- WRN.[35][49] | https://www.wikidoc.org/index.php/DNA-PKcs | |
3c830ce7cafea0164d85093abf21d0d740b98fbf | wikidoc | DNASE1L2 | DNASE1L2
Deoxyribonuclease-1-like 2 is an enzyme that in humans is encoded by the DNASE1L2 gene.
# Model organisms
Model organisms have been used in the study of DNASE1L2 function. A conditional knockout mouse line, called Dnase1l2tm1(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and eight significant abnormalities were observed. Homozygous mutant animals had a decreased body weight, grip strength and bone mineral content; a kinked tail, abnormal indirect calorimetry and femur/tibia morphology. Females also had an increased blood urea nitrogen level while males had a decreased leukocyte cell number. | DNASE1L2
Deoxyribonuclease-1-like 2 is an enzyme that in humans is encoded by the DNASE1L2 gene.[1][2][3]
# Model organisms
Model organisms have been used in the study of DNASE1L2 function. A conditional knockout mouse line, called Dnase1l2tm1(KOMP)Wtsi[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[18][19][20]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty three tests were carried out on mutant mice and eight significant abnormalities were observed.[14] Homozygous mutant animals had a decreased body weight, grip strength and bone mineral content; a kinked tail, abnormal indirect calorimetry and femur/tibia morphology. Females also had an increased blood urea nitrogen level while males had a decreased leukocyte cell number.[14] | https://www.wikidoc.org/index.php/DNASE1L2 | |
03d2cfa057adfb82fa1e3c96f4bab0e16be9d7e5 | wikidoc | Mutation | Mutation
In biology, mutations are changes to the base pair sequence of the genetic material of an organism. Mutations can be caused by copying errors in the genetic material during cell division, by exposure to ultraviolet or ionizing radiation, chemical mutagens, or viruses, or can occur deliberately under cellular control during processes such as hypermutation. In multicellular organisms, mutations can be subdivided into germ line mutations, which can be passed on to descendants, and somatic mutations, which cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant). A new mutation that was not inherited from either parent is called a de novo mutation.
Mutations create variations in the gene pool, and the less favorable (or deleterious) mutations are reduced in frequency in the gene pool by natural selection, while more favorable (beneficial or advantageous) mutations tend sisto accumulate, resulting in evolutionary change. For example, a butterfly may produce offspring with a new mutation caused by ultraviolet light from the sun. In most cases, this mutation is not good, since obviously there was no 'purpose' for such change at the molecular level. However, sometimes a mutation may change the butterfly's color, making it harder for predators to see it; this is an advantage and the chances of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a large percentage of the species.
Neutral mutations are defined as mutations whose effects do not influence the fitness of either the species or the individuals who make up the species. These can accumulate over time due to genetic drift. The overwhelming majority of mutations have no significant effect, since DNA repair is able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.
# Classification
## By effect on structure
The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:
- Small-scale mutations, such as affecting a small gene is one or a few nucleotides, including:
Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mis-pairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
Silent mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and can truncate the protein.
Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.
Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
- Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mis-pairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
Silent mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and can truncate the protein.
- Silent mutations: which code for the same amino acid.
- Missense mutations: which code for a different amino acid.
- Nonsense mutations: which code for a stop and can truncate the protein.
- Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.
- Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
- Large-scale mutations in chromosomal structure, including:
Amplifications (or gene duplications) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
Deletions of large chromosomal regions, leading to loss of the genes within those regions.
Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
Chromosomal inversions: reversing the orientation of a chromosomal segment.
Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in an organism that previously had two different alleles.
- Amplifications (or gene duplications) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
- Deletions of large chromosomal regions, leading to loss of the genes within those regions.
- Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
Chromosomal inversions: reversing the orientation of a chromosomal segment.
- Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
- Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
- Chromosomal inversions: reversing the orientation of a chromosomal segment.
- Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in an organism that previously had two different alleles.
## By effect on function
- Loss-of-function mutations are the result of gene product having less or no function. When the allele has a complete loss of function (null allele) it is often called an amorphic mutation. Phenotypes associated with such mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called haploinsufficiency).
- Gain-of-function mutations change the gene product such that it gains a new and abnormal function. These mutations usually have dominant phenotypes. Often called a neo-morphic mutation.
- Dominant negative mutations (also called anti-morphic mutations) have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a dominant or semi-dominant phenotype. In humans, Marfan syndrome is an example of a dominant negative mutation occurring in an autosomal dominant disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.
- Lethal mutations are mutations that lead to a phenotype incapable of effective reproduction.
## By aspect of phenotype affected
- Morphological mutations usually affect the outward appearance of an individual. Mutations can change the height of a plant or change it from smooth to rough seeds.
- Biochemical mutations result in lesions stopping the enzymatic pathway. Often, morphological mutants are the direct result of a mutation due to the enzymatic pathway.
## Special classes
- Conditional mutation is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deleterious consequences at a lower temperature (permissive condition).
## Causes of mutation
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.
Spontaneous mutations on the molecular level include:
- Tautomerism - A base is changed by the repositioning of a hydrogen atom.
- Depurination - Loss of a purine base (A or G).
- Deamination - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), or spontaneous deamination of 5-methycytosine (irreparable), or A → HX (hypoxanthine).
- Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine.
- Transversion - A purine becomes a pyrimidine, or vice versa.
Induced mutations on the molecular level can be caused by:
- Chemicals
Nitrosoguanidine (NTG)
Hydroxylamine NH2OH
Base analogs (e.g. BrdU)
Simple chemicals (e.g. acids)
Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
Methylating agents (e.g. ethyl methanesulfonate (EMS))
Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
DNA intercalating agents (e.g. ethidium bromide)
DNA crosslinker (e.g. platinum)
Oxidative damage caused by oxygen(O)] radicals
- Nitrosoguanidine (NTG)
- Hydroxylamine NH2OH
- Base analogs (e.g. BrdU)
- Simple chemicals (e.g. acids)
- Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
- Methylating agents (e.g. ethyl methanesulfonate (EMS))
- Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
- DNA intercalating agents (e.g. ethidium bromide)
- DNA crosslinker (e.g. platinum)
- Oxidative damage caused by oxygen(O)] radicals
- Radiation
Ultraviolet radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
Ionizing radiation
- Ultraviolet radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
- Ionizing radiation
DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine.
Mutation rates also vary across species. Evolutionary biologists have theorized that higher mutation rates are beneficial in some situations, because they allow organisms to evolve and therefore adapt more quickly to their environments. For example, repeated exposure of bacteria to antibiotics, and selection of resistant mutants, can result in the selection of bacteria that have a much higher mutation rate than the original population (mutator strains).
## Nomenclature
Nomenclature of mutations specify the type of mutation and base or amino acid changes.
- Amino acid substitution - (e.g. D111E) The first letter is the one letter code of the wildtype amino acid, the number is the position of the amino acid from the N terminus and the second letter is the one letter code of the amino acid present in the mutation. If the second letter is 'X', any amino acid may replace the wildtype.
- Amino acid deletion - (e.g. ΔF508) The Greek symbol Δ or 'delta' indicates a deletion. The letter refers to the amino acid present in the wildtype and the number is the position from the N terminus of the amino acid were it to be present as in the wildtype.
# Types of mutations
## Adaptive mutation
In mainstream biological thought it is held that while mutagenesis is non-random in many ways, the utility of a genetic mutation to the organism in which it occurs does not affect the rate at which it occurs. However experimental evidence exists that in some instances the rate of specific mutations arising is greater when they are advantageous to the organism than when they are not.
## Back mutation
Back mutation is a change in a nucleotide pair of a point-mutated DNA sequence that restores the original sequence and hence the original phenotype.
## Frameshift mutation
A frameshift mutation is a mutation caused by indels, ie. inserts or deletes a number of nucleotides that is not evenly divisible by three from a DNA sequence. Due to the triplet nature of gene expression by codons, the insertion or deletion can disrupt the reading frame, or the grouping of the codons, resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein produced is.
## Missense mutation
Missense mutations or nonsynonymous mutations are types of point mutations where a single nucleotide is changed to cause substitution of a different amino acid. This in turn can render the resulting protein nonfunctional. Such mutations are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALSTemplate:Harv.
## Neutral mutation
A neutral mutation is a mutation that occurs in an amino acid codon (presumably within an mRNA molecule) which results in the use of a different, but chemically similar, amino acid. This is similar to a silent mutation, where a codon mutation may encode the same amino acid (see Wobble Hypothesis); for example, a change from AUU to AUC will still encode leucine, so no discernable change occurs (a silent mutation).
## Nonsense mutation
A nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and possibly a truncated, and often nonfunctional protein product.
## Point mutation
A point mutation, or substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. Often the term point mutation also includes insertions or deletions of a single base pair (which have more of an adverse effect on the synthesized protein due to nucleotides still being read in triplets, but in different frames- a mutation called a frameshift mutation).
## Silent mutation
Silent mutations are DNA mutations that do not result in a change to the amino acid sequence of a protein. They may occur in a non-coding region (outside of a gene or within an intron), or they may occur within an exon in a manner that does not alter the final amino acid sequence. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are a subcategory of the former, occurring only within exons.
# Harmful mutations
Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional proteins. To function correctly, each cell depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. A condition caused by mutations in one or more genes is called a genetic disorder. However, only a small percentage of mutations cause genetic disorders; most have no impact on health. For example, some mutations alter a gene's DNA base sequence but don’t change the function of the protein made by the gene.
If a mutation is present in a germ cell, it can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. On the other hand, a mutation can occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell, and certain mutations can cause the cell to become malignant, and thus cause cancer.
Often, gene mutations that could cause a genetic disorder are repaired by the DNA repair system of the cell. Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, the process of DNA repair is an important way in which the body protects itself from disease.
# Beneficial mutations
A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes. The CCR5 mutation is more common in those of European descent. One theory for the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People who had this mutation were able to survive infection thus its frequency in the population increased. It could also explain why this mutation is not found in Africa where the bubonic plague never reached. Newer theory says the selective pressure on the CCR5 Delta 32 mutation has been caused by smallpox instead of bubonic plague. | Mutation
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In biology, mutations are changes to the base pair sequence of the genetic material of an organism. Mutations can be caused by copying errors in the genetic material during cell division, by exposure to ultraviolet or ionizing radiation, chemical mutagens, or viruses, or can occur deliberately under cellular control during processes such as hypermutation. In multicellular organisms, mutations can be subdivided into germ line mutations, which can be passed on to descendants, and somatic mutations, which cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant). A new mutation that was not inherited from either parent is called a de novo mutation.
Mutations create variations in the gene pool, and the less favorable (or deleterious) mutations are reduced in frequency in the gene pool by natural selection, while more favorable (beneficial or advantageous) mutations tend sisto accumulate, resulting in evolutionary change. For example, a butterfly may produce offspring with a new mutation caused by ultraviolet light from the sun. In most cases, this mutation is not good, since obviously there was no 'purpose' for such change at the molecular level. However, sometimes a mutation may change the butterfly's color, making it harder for predators to see it; this is an advantage and the chances of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a large percentage of the species.
Neutral mutations are defined as mutations whose effects do not influence the fitness of either the species or the individuals who make up the species. These can accumulate over time due to genetic drift. The overwhelming majority of mutations have no significant effect, since DNA repair is able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.
# Classification
## By effect on structure
The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:
- Small-scale mutations, such as affecting a small gene is one or a few nucleotides, including:
Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mis-pairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
Silent mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and can truncate the protein.
Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.
Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
- Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mis-pairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
Silent mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and can truncate the protein.
- Silent mutations: which code for the same amino acid.
- Missense mutations: which code for a different amino acid.
- Nonsense mutations: which code for a stop and can truncate the protein.
- Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.
- Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
- Large-scale mutations in chromosomal structure, including:
Amplifications (or gene duplications) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
Deletions of large chromosomal regions, leading to loss of the genes within those regions.
Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
Chromosomal inversions: reversing the orientation of a chromosomal segment.
Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in an organism that previously had two different alleles.
- Amplifications (or gene duplications) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
- Deletions of large chromosomal regions, leading to loss of the genes within those regions.
- Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
Chromosomal inversions: reversing the orientation of a chromosomal segment.
- Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
- Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
- Chromosomal inversions: reversing the orientation of a chromosomal segment.
- Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in an organism that previously had two different alleles.
## By effect on function
- Loss-of-function mutations are the result of gene product having less or no function. When the allele has a complete loss of function (null allele) it is often called an amorphic mutation. Phenotypes associated with such mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called haploinsufficiency).
- Gain-of-function mutations change the gene product such that it gains a new and abnormal function. These mutations usually have dominant phenotypes. Often called a neo-morphic mutation.
- Dominant negative mutations (also called anti-morphic mutations) have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a dominant or semi-dominant phenotype. In humans, Marfan syndrome is an example of a dominant negative mutation occurring in an autosomal dominant disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.
- Lethal mutations are mutations that lead to a phenotype incapable of effective reproduction.
## By aspect of phenotype affected
- Morphological mutations usually affect the outward appearance of an individual. Mutations can change the height of a plant or change it from smooth to rough seeds.
- Biochemical mutations result in lesions stopping the enzymatic pathway. Often, morphological mutants are the direct result of a mutation due to the enzymatic pathway.
## Special classes
- Conditional mutation is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deleterious consequences at a lower temperature (permissive condition).
## Causes of mutation
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.
Spontaneous mutations on the molecular level include:
- Tautomerism - A base is changed by the repositioning of a hydrogen atom.
- Depurination - Loss of a purine base (A or G).
- Deamination - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), or spontaneous deamination of 5-methycytosine (irreparable), or A → HX (hypoxanthine).
- Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine.
- Transversion - A purine becomes a pyrimidine, or vice versa.
Induced mutations on the molecular level can be caused by:
- Chemicals
Nitrosoguanidine (NTG)
Hydroxylamine NH2OH
Base analogs (e.g. BrdU)
Simple chemicals (e.g. acids)
Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
Methylating agents (e.g. ethyl methanesulfonate (EMS))
Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
DNA intercalating agents (e.g. ethidium bromide)
DNA crosslinker (e.g. platinum)
Oxidative damage caused by oxygen(O)] radicals
- Nitrosoguanidine (NTG)
- Hydroxylamine NH2OH
- Base analogs (e.g. BrdU)
- Simple chemicals (e.g. acids)
- Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
- Methylating agents (e.g. ethyl methanesulfonate (EMS))
- Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
- DNA intercalating agents (e.g. ethidium bromide)
- DNA crosslinker (e.g. platinum)
- Oxidative damage caused by oxygen(O)] radicals
- Radiation
Ultraviolet radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
Ionizing radiation
- Ultraviolet radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
- Ionizing radiation
DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine.
Mutation rates also vary across species. Evolutionary biologists have theorized that higher mutation rates are beneficial in some situations, because they allow organisms to evolve and therefore adapt more quickly to their environments. For example, repeated exposure of bacteria to antibiotics, and selection of resistant mutants, can result in the selection of bacteria that have a much higher mutation rate than the original population (mutator strains).
## Nomenclature
Nomenclature of mutations specify the type of mutation and base or amino acid changes.
- Amino acid substitution - (e.g. D111E) The first letter is the one letter code of the wildtype amino acid, the number is the position of the amino acid from the N terminus and the second letter is the one letter code of the amino acid present in the mutation. If the second letter is 'X', any amino acid may replace the wildtype.
- Amino acid deletion - (e.g. ΔF508) The Greek symbol Δ or 'delta' indicates a deletion. The letter refers to the amino acid present in the wildtype and the number is the position from the N terminus of the amino acid were it to be present as in the wildtype.
# Types of mutations
## Adaptive mutation
In mainstream biological thought it is held that while mutagenesis is non-random in many ways, the utility of a genetic mutation to the organism in which it occurs does not affect the rate at which it occurs. However experimental evidence exists that in some instances the rate of specific mutations arising is greater when they are advantageous to the organism than when they are not.
## Back mutation
Back mutation is a change in a nucleotide pair of a point-mutated DNA sequence that restores the original sequence and hence the original phenotype.[1]
## Frameshift mutation
A frameshift mutation is a mutation caused by indels, ie. inserts or deletes a number of nucleotides that is not evenly divisible by three from a DNA sequence. Due to the triplet nature of gene expression by codons, the insertion or deletion can disrupt the reading frame, or the grouping of the codons, resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein produced is.
## Missense mutation
Missense mutations or nonsynonymous mutations are types of point mutations where a single nucleotide is changed to cause substitution of a different amino acid. This in turn can render the resulting protein nonfunctional. Such mutations are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALSTemplate:Harv.
## Neutral mutation
A neutral mutation is a mutation that occurs in an amino acid codon (presumably within an mRNA molecule) which results in the use of a different, but chemically similar, amino acid. This is similar to a silent mutation, where a codon mutation may encode the same amino acid (see Wobble Hypothesis); for example, a change from AUU to AUC will still encode leucine, so no discernable change occurs (a silent mutation).
## Nonsense mutation
A nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and possibly a truncated, and often nonfunctional protein product.
## Point mutation
A point mutation, or substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. Often the term point mutation also includes insertions or deletions of a single base pair (which have more of an adverse effect on the synthesized protein due to nucleotides still being read in triplets, but in different frames- a mutation called a frameshift mutation).
## Silent mutation
Silent mutations are DNA mutations that do not result in a change to the amino acid sequence of a protein. They may occur in a non-coding region (outside of a gene or within an intron), or they may occur within an exon in a manner that does not alter the final amino acid sequence. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are a subcategory of the former, occurring only within exons.
# Harmful mutations
Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional proteins. To function correctly, each cell depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. A condition caused by mutations in one or more genes is called a genetic disorder. However, only a small percentage of mutations cause genetic disorders; most have no impact on health. For example, some mutations alter a gene's DNA base sequence but don’t change the function of the protein made by the gene.
If a mutation is present in a germ cell, it can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. On the other hand, a mutation can occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell, and certain mutations can cause the cell to become malignant, and thus cause cancer[2].
Often, gene mutations that could cause a genetic disorder are repaired by the DNA repair system of the cell. Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, the process of DNA repair is an important way in which the body protects itself from disease.
# Beneficial mutations
A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes.[3] The CCR5 mutation is more common in those of European descent. One theory for the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People who had this mutation were able to survive infection thus its frequency in the population increased.[4] It could also explain why this mutation is not found in Africa where the bubonic plague never reached. Newer theory says the selective pressure on the CCR5 Delta 32 mutation has been caused by smallpox instead of bubonic plague.[5] | https://www.wikidoc.org/index.php/DNA_mutations | |
b0ea6faab8932adaa545ac0721cacdb669aed5b5 | wikidoc | Levodopa | Levodopa
# Overview
Levodopa (INN) or L-DOPA (3,4-dihydroxy-L-phenylalanine) is an intermediate in dopamine biosynthesis. In clinical use, levodopa is administered in the management of Parkinson's disease.
# Therapeutic use
Levodopa is used as a prodrug to increase dopamine levels for the treatment of Parkinson's disease, since it is able to cross the blood-brain barrier, whereas dopamine itself cannot. Once levodopa has entered the central nervous system (CNS), it is metabolized to dopamine by aromatic L-amino acid decarboxylase. However, conversion to dopamine also occurs in the peripheral tissues, causing adverse effects and decreasing the available dopamine to the CNS, so it is standard practice to co-administer a peripheral DOPA decarboxylase inhibitor – carbidopa or benserazide – and often a catechol-O-methyl transferase (COMT) inhibitor. However, Vitamin-B6 (pyridoxine) inhibits the conversion of levodopa to dopamine. Thus, it is necessary to limit pyridoxine intake, but with extreme care in dosing, for vitamin-B6 deficiency can lead to paresthesias, numbness of extremities, mental confusion, and depression.
# Adverse effects
Possible adverse drug reactions include:
- Hypotension, especially if the dosage is too high
- Arrhythmias, although these are uncommon
- Nausea, which is often helped by taking the drug with food, although protein interferes with drug absorption
- Gastrointestinal bleeding
- Disturbed respiration, which is not always harmful, and can actually benefit patients with upper airway obstruction
- Hair loss
- Confusion
- Extreme emotional states, particularly anxiety, but also excessive libido
- Vivid dreams and/or fragmented sleep
- Visual and possibly auditory hallucinations
- Effects on learning; there is some evidence that it improves working memory, while impairing other complex functions
- Sleepiness and sleep attacks
- A condition similar to amphetamine psychosis.
Although there are many adverse effects associated with levodopa, particularly psychiatric ones, it has fewer than other anti-Parkinson's drugs, including anticholinergics, amantadine, and dopamine agonists.
More serious are the effects of chronic levodopa administration, which include:
- End-of-dose deterioration of function
- On/off oscillations
- Freezing during movement
- Dose failure (drug resistance)
- Dyskinesia at peak dose.
Clinicians will try to avoid these by limiting levodopa dosages as far as possible until absolutely necessary.
# Biosynthesis
L-DOPA is produced from the amino acid tyrosine by the enzyme tyrosine hydroxylase. It is also the precursor molecule for the catecholamine neurotransmitters dopamine and norepinephrine (noradrenaline), and the hormone epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.
The prefix L- references its property of levorotation (compared with dextrorotation or D-DOPA).
# History
In work that earned him a Nobel Prize in 2000, Swedish scientist Arvid Carlsson first showed in the 1950s that administering levodopa to animals with Parkinsonian symptoms would cause a reduction of the symptoms. The neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his book Awakenings, upon which the movie Awakenings is based.
The 2001 Nobel Prize in Chemistry was also related to L-DOPA: the Nobel Committee awarded one-fourth of the prize to William S. Knowles for his work on chirally-catalysed hydrogenation reactions, the most noted example of which was used for the synthesis of L-DOPA.
# Supplements containing L-DOPA
Herbal supplements containing standardized dosages of L-DOPA are available without a prescription. These supplements have recently increased in both availability and popularity in the United States and on the Internet. The most common plant source of L-DOPA marketed in this manner is a tropical legume, Mucuna pruriens, also known as "Velvet Bean" and by a number of other common names.
Two of the most popular brands of Mucuna pruriens are "DopaBean," marketed by Solaray, and "Mucuna," marketed by Physician Formulas, Inc. These preparations claim to contain standardized dosages of L-DOPA in enteric-coated capsules. The dosage claimed is usually about 50 mg per capsule, and the recommended dose is two capsules per day. A third product, "L-Dopa," marketed by Unique Nutrition, claims a higher effective dose of 250 mg. American Nutrition also carries a Mucuna pruriens standardized to 40% L-DOPA under its NutraceuticsRx label.
Some of the claims made for the use of these supplements may have validity, whereas many do not. Among the most common claims are that the supplements will increase libido and aid in body-building (presumably by increasing human growth hormone in both cases). The long-term consequences of the use of these supplements by healthy individuals remains to be seen.
# Adhesion
DOPA is a key molecule in the formation of marine adhesive proteins, such as those found in mussels. It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.
# Melanin formation
Both levodopa and the related amino acid L-tyrosine are precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of L-dopa to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. | Levodopa
For patient information, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Levodopa (INN) or L-DOPA (3,4-dihydroxy-L-phenylalanine) is an intermediate in dopamine biosynthesis. In clinical use, levodopa is administered in the management of Parkinson's disease.
# Therapeutic use
Levodopa is used as a prodrug to increase dopamine levels for the treatment of Parkinson's disease, since it is able to cross the blood-brain barrier, whereas dopamine itself cannot. Once levodopa has entered the central nervous system (CNS), it is metabolized to dopamine by aromatic L-amino acid decarboxylase. However, conversion to dopamine also occurs in the peripheral tissues, causing adverse effects and decreasing the available dopamine to the CNS, so it is standard practice to co-administer a peripheral DOPA decarboxylase inhibitor – carbidopa or benserazide – and often a catechol-O-methyl transferase (COMT) inhibitor. However, Vitamin-B6 (pyridoxine) inhibits the conversion of levodopa to dopamine. Thus, it is necessary to limit pyridoxine intake, but with extreme care in dosing, for vitamin-B6 deficiency can lead to paresthesias, numbness of extremities, mental confusion, and depression.
# Adverse effects
Possible adverse drug reactions include:
- Hypotension, especially if the dosage is too high
- Arrhythmias, although these are uncommon
- Nausea, which is often helped by taking the drug with food, although protein interferes with drug absorption
- Gastrointestinal bleeding
- Disturbed respiration, which is not always harmful, and can actually benefit patients with upper airway obstruction
- Hair loss
- Confusion
- Extreme emotional states, particularly anxiety, but also excessive libido
- Vivid dreams and/or fragmented sleep
- Visual and possibly auditory hallucinations
- Effects on learning; there is some evidence that it improves working memory, while impairing other complex functions
- Sleepiness and sleep attacks
- A condition similar to amphetamine psychosis.
Although there are many adverse effects associated with levodopa, particularly psychiatric ones, it has fewer than other anti-Parkinson's drugs, including anticholinergics, amantadine, and dopamine agonists.
More serious are the effects of chronic levodopa administration, which include:
- End-of-dose deterioration of function
- On/off oscillations
- Freezing during movement
- Dose failure (drug resistance)
- Dyskinesia at peak dose.
Clinicians will try to avoid these by limiting levodopa dosages as far as possible until absolutely necessary.
# Biosynthesis
L-DOPA is produced from the amino acid tyrosine by the enzyme tyrosine hydroxylase. It is also the precursor molecule for the catecholamine neurotransmitters dopamine and norepinephrine (noradrenaline), and the hormone epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.
The prefix L- references its property of levorotation (compared with dextrorotation or D-DOPA).
# History
In work that earned him a Nobel Prize in 2000, Swedish scientist Arvid Carlsson first showed in the 1950s that administering levodopa to animals with Parkinsonian symptoms would cause a reduction of the symptoms. The neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his book Awakenings, upon which the movie Awakenings is based.
The 2001 Nobel Prize in Chemistry was also related to L-DOPA: the Nobel Committee awarded one-fourth of the prize to William S. Knowles for his work on chirally-catalysed hydrogenation reactions, the most noted example of which was used for the synthesis of L-DOPA.
# Supplements containing L-DOPA
Herbal supplements containing standardized dosages of L-DOPA are available without a prescription. These supplements have recently increased in both availability and popularity in the United States and on the Internet. The most common plant source of L-DOPA marketed in this manner is a tropical legume, Mucuna pruriens, also known as "Velvet Bean" and by a number of other common names.
Two of the most popular brands of Mucuna pruriens are "DopaBean," marketed by Solaray, and "Mucuna," marketed by Physician Formulas, Inc. These preparations claim to contain standardized dosages of L-DOPA in enteric-coated capsules. The dosage claimed is usually about 50 mg per capsule, and the recommended dose is two capsules per day. A third product, "L-Dopa," marketed by Unique Nutrition, claims a higher effective dose of 250 mg. American Nutrition also carries a Mucuna pruriens standardized to 40% L-DOPA under its NutraceuticsRx label.
Some of the claims made for the use of these supplements may have validity, whereas many do not. Among the most common claims are that the supplements will increase libido and aid in body-building (presumably by increasing human growth hormone in both cases). The long-term consequences of the use of these supplements by healthy individuals remains to be seen.
# Adhesion
DOPA is a key molecule in the formation of marine adhesive proteins, such as those found in mussels. It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.
# Melanin formation
Both levodopa and the related amino acid L-tyrosine are precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of L-dopa to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. | https://www.wikidoc.org/index.php/DOPA | |
99ac9eb9b01d377ac5a27e07869bd93a7b2135a8 | wikidoc | Torsin A | Torsin A
Torsin-1A (TorA) also known as dystonia 1 protein (DYT1) is a protein that in humans is encoded by the TOR1A gene (also known as DQ2 or DYT1). TorA localizes to the endoplasmic reticulum and contiguous perinuclear space, where its ATPase activity is activated by either LULL1 or LAP1, respectively.
# Function
The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family and is expressed prominently in the substantia nigra pars compacta.
# Clinical significance
Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1. | Torsin A
Torsin-1A (TorA) also known as dystonia 1 protein (DYT1) is a protein that in humans is encoded by the TOR1A gene (also known as DQ2 or DYT1).[1] TorA localizes to the endoplasmic reticulum and contiguous perinuclear space, where its ATPase activity is activated by either LULL1 or LAP1, respectively.
# Function
The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family and is expressed prominently in the substantia nigra pars compacta.[2]
# Clinical significance
Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1.[2] | https://www.wikidoc.org/index.php/DYT1 | |
a320834a655bcbaaa33b18caa316b42cc6d7ce15 | wikidoc | Dactylis | Dactylis
# Overview
Dactylis is a genus of grasses in the subfamily Pooideae, native to Europe, Asia, and northern Africa. They are known in English as cock's-foot or cocksfoot grasses, also sometimes as orchard grasses.
# Taxonomy
The genus has been treated as containing only a single species D. glomerata by many authors, treating variation in the genus at only subspecific rank within D. glomerata, but more recently, there has been a trend to accept two species, while some authors accept even more species in the genus, particularly island endemic species in Macaronesia.
# Description
Dactylis species are perennial grasses, forming dense tussocks growing to 15–140 centimetres tall, with leaves 20–50 cm long and up to 1.5 cm broad, and distinctive tufted triangular flowerheads comprising a panicle 10–15 cm long, turning pale grey-brown at seed maturity. The spikelets are 5–9 mm long, typically containing two to five flowers. The stems have a flattened base, which distinguishes them from many other grasses.
# Species
- Dactylis glomerata L. Throughout most of the range of the genus.
- Dactylis marina Borrill. Western Mediterranean region (SW Europe, NW Africa).
- Dactylis metlesicsii Schönfelder & Ludwig. Canary Islands, endemic.
- Dactylis smithii Link (syn. D. glomerata subsp. smithii (Link) Stebbins & Zohary). Canary Islands, Cape Verde, Madeira.
# Cytology
The taxa show several different levels of polyploidy. Dactylis glomerata subsp. glomerata and D. glomerata subsp. hispanica are tetraploid forms with 28 chromosomes. Several of the other taxa, including D. glomerata. subsp. himalayensis (syn. D. himalayensis), D. glomerata subsp. lobata (syn. D. polygama), D. metlesicsii, and some forms of D. smithii, are diploid with 2n = 14; hexaploids with 42 chromosomes also occur rarely. | Dactylis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dactylis is a genus of grasses in the subfamily Pooideae, native to Europe, Asia, and northern Africa. They are known in English as cock's-foot or cocksfoot grasses, also sometimes as orchard grasses.
# Taxonomy
The genus has been treated as containing only a single species D. glomerata by many authors, treating variation in the genus at only subspecific rank within D. glomerata,[1][2][3] but more recently, there has been a trend to accept two species,[4] while some authors accept even more species in the genus, particularly island endemic species in Macaronesia.[5][6][7][8]
# Description
Dactylis species are perennial grasses, forming dense tussocks growing to 15–140 centimetres tall, with leaves 20–50 cm long and up to 1.5 cm broad, and distinctive tufted triangular flowerheads comprising a panicle 10–15 cm long, turning pale grey-brown at seed maturity. The spikelets are 5–9 mm long, typically containing two to five flowers. The stems have a flattened base, which distinguishes them from many other grasses.[2][9][10][11]
# Species
- Dactylis glomerata L. Throughout most of the range of the genus.
- Dactylis marina Borrill. Western Mediterranean region (SW Europe, NW Africa).
- Dactylis metlesicsii Schönfelder & Ludwig. Canary Islands, endemic.
- Dactylis smithii Link (syn. D. glomerata subsp. smithii (Link) Stebbins & Zohary). Canary Islands, Cape Verde, Madeira.
# Cytology
The taxa show several different levels of polyploidy. Dactylis glomerata subsp. glomerata and D. glomerata subsp. hispanica are tetraploid forms with 28 chromosomes. Several of the other taxa, including D. glomerata. subsp. himalayensis (syn. D. himalayensis), D. glomerata subsp. lobata (syn. D. polygama), D. metlesicsii, and some forms of D. smithii, are diploid with 2n = 14; hexaploids with 42 chromosomes also occur rarely.[2][6][12] | https://www.wikidoc.org/index.php/Dactylis | |
3392c9bec1499cb39d39363467f74ecd840c5441 | wikidoc | Dezocine | Dezocine
# Overview
Dezocine (Dalgan, WY-16225) is an opioid analgesic related to pentazocine, with a similar profile of effects that include analgesic action and euphoria at low doses, but produces dysphoria and hallucinations at high doses, most likely due to action at κ-opioid receptors.
Dezocine has been found to be an effective painkiller comparable to meperidine (pethidine), and so is a more effective analgesic than pentazocine, but causes relatively more respiratory depression than pentazocine. It is a useful drug for the treatment of pain, but side effects such as dizziness limit its clinical application, and it can produce opioid withdrawal syndrome in patients already dependent on other opioids.
Dezocine is unusual among opioids as it is the only primary amine known to be an active opioid. It is a mixed agonist-antagonist as with other drugs in this class, and despite having a stronger respiratory depressant effect than morphine, dezocine shows a ceiling effect on its respiratory depressive action so above a certain dose this effect does not get any more severe. | Dezocine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dezocine (Dalgan, WY-16225) is an opioid analgesic related to pentazocine, with a similar profile of effects that include analgesic action and euphoria at low doses,[1] but produces dysphoria and hallucinations at high doses, most likely due to action at κ-opioid receptors.[2][3]
Dezocine has been found to be an effective painkiller comparable to meperidine (pethidine),[4] and so is a more effective analgesic than pentazocine, but causes relatively more respiratory depression than pentazocine.[5] It is a useful drug for the treatment of pain,[6] but side effects such as dizziness limit its clinical application,[7] and it can produce opioid withdrawal syndrome in patients already dependent on other opioids.[8]
Dezocine is unusual among opioids as it is the only primary amine known to be an active opioid. It is a mixed agonist-antagonist as with other drugs in this class,[9] and despite having a stronger respiratory depressant effect than morphine, dezocine shows a ceiling effect on its respiratory depressive action so above a certain dose this effect does not get any more severe.[10]
Template:Pharm-stub | https://www.wikidoc.org/index.php/Dalgan | |
5da667758182442fd8cc9c349bb325b98acf7758 | wikidoc | Dandruff | Dandruff
Dandruff (also called scurf and historically termed Pityriasis capitis) is due to the excessive shedding of dead skin cells from the scalp. As it is normal for skin cells to die and flake off, a small amount of flaking is normal and in fact quite common. Some people, however, either chronically or as a result of certain triggers, experience an unusually large amount of flaking, which can also be accompanied by redness and irritation. Most cases of dandruff can be easily treated with specialized shampoos. Dandruff is not an organism like lice; it is just dead skin that accumulates in the scalp. Dandruff is unlikely to be the cause of hair loss.
Excessive flaking can also be a symptom of seborrhoeic dermatitis, psoriasis, fungal infection or excoriation associated with infestation of head lice.
Dandruff is a global phenomenon and many people find that dandruff can cause social or self-esteem problems. Treatment may be important purely for psychological reasons.
# Causes
As the epidermal layer continually replaces itself, cells are pushed outward where they eventually die and flake off. In most people, these flakes of skin are too small to be visible. However, certain conditions cause cell turnover to be unusually rapid, especially in the scalp. For people with dandruff, skin cells may mature and be shed in 2 - 7 days, as opposed to around a month in people without dandruff. The result is that dead skin cells are shed in large, oily clumps, which appear as white or grayish patches on the scalp skin and clothes.
Dandruff has been shown to be the result of three required factors:
- Skin oil commonly referred to as sebum or sebaceous secretions
- The metabolic by-products of skin micro-organisms (most specifically Malassezia yeasts)
- Individual susceptibility
Common older literature cites the fungus Malassezia furfur (previously known as Pityrosporum ovale) as the cause of dandruff. While this fungus is found naturally on the skin surface of both healthy people and those with dandruff, it has recently been shown that a scalp specific fungus, Malassezia globosa, is the responsible agent. This fungus metabolizes triglycerides present in sebum by the expression of lipase, resulting in a lipid byproduct oleic acid (OA). Penetration by OA of the top layer of the epidermis, the stratum corneum, results in an inflammatory response in susceptible persons which disturbs homeostasis and results in erratic cleavage of stratum corneum cells.
Rarely, dandruff can be a manifestation of an allergic reaction to chemicals in hair gels/sprays, hair oils, or sometimes even dandruff medications like ketoconazole.
There is no convincing evidence that food (such as sugar or yeast), excessive perspiration, or climate have any role in the pathogenesis of dandruff.
# Seborrheic dermatitis
Flaking is a symptom of seborrheic dermatitis. Joseph Bark notes that "Redness and itching is actually seborrheic dermatitis, and it frequently occurs around the folds of the nose and the eyebrow areas, not just the scalp." Dry, thick, well-defined lesions consisting of large, silvery scales may be traced to the less common psoriasis of the scalp.
Seasonal changes, stress, and immuno-suppression seem to affect seborrheic dermatitis.
# Treatment
There have been many strategies for the control of dandruff. Simply increasing shampooing will remove flakes. However, elimination of the fungus results in dramatic improvement. Regular shampooing with an anti-fungal product can reduce recurrence.
Anti-fungal/anti-dandruff shampoos containing ketoconazole have been shown to be more effective than zinc pyrithione. Ketoconazole is the most effective antifungal agent concluded by multiple studies. | Dandruff
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Dandruff (also called scurf and historically termed Pityriasis capitis) is due to the excessive shedding of dead skin cells from the scalp. As it is normal for skin cells to die and flake off, a small amount of flaking is normal and in fact quite common. Some people, however, either chronically or as a result of certain triggers, experience an unusually large amount of flaking, which can also be accompanied by redness and irritation. Most cases of dandruff can be easily treated with specialized shampoos. Dandruff is not an organism like lice; it is just dead skin that accumulates in the scalp. Dandruff is unlikely to be the cause of hair loss.
Excessive flaking can also be a symptom of seborrhoeic dermatitis, psoriasis, fungal infection or excoriation associated with infestation of head lice.
Dandruff is a global phenomenon and many people find that dandruff can cause social or self-esteem problems. Treatment may be important purely for psychological reasons.
# Causes
As the epidermal layer continually replaces itself, cells are pushed outward where they eventually die and flake off. In most people, these flakes of skin are too small to be visible. However, certain conditions cause cell turnover to be unusually rapid, especially in the scalp. For people with dandruff, skin cells may mature and be shed in 2 - 7 days, as opposed to around a month in people without dandruff. The result is that dead skin cells are shed in large, oily clumps, which appear as white or grayish patches on the scalp skin and clothes.
Dandruff has been shown to be the result of three required factors:[1]
- Skin oil commonly referred to as sebum or sebaceous secretions[2]
- The metabolic by-products of skin micro-organisms (most specifically Malassezia yeasts)[3][4][5][6][7]
- Individual susceptibility
Common older literature cites the fungus Malassezia furfur (previously known as Pityrosporum ovale) as the cause of dandruff. While this fungus is found naturally on the skin surface of both healthy people and those with dandruff, it has recently been shown that a scalp specific fungus, Malassezia globosa, is the responsible agent. This fungus metabolizes triglycerides present in sebum by the expression of lipase, resulting in a lipid byproduct oleic acid (OA). Penetration by OA of the top layer of the epidermis, the stratum corneum, results in an inflammatory response in susceptible persons which disturbs homeostasis and results in erratic cleavage of stratum corneum cells.[5]
Rarely, dandruff can be a manifestation of an allergic reaction to chemicals in hair gels/sprays, hair oils, or sometimes even dandruff medications like ketoconazole.
There is no convincing evidence that food (such as sugar or yeast), excessive perspiration, or climate have any role in the pathogenesis of dandruff.
# Seborrheic dermatitis
Flaking is a symptom of seborrheic dermatitis. Joseph Bark notes that "Redness and itching is actually seborrheic dermatitis, and it frequently occurs around the folds of the nose and the eyebrow areas, not just the scalp." Dry, thick, well-defined lesions consisting of large, silvery scales may be traced to the less common psoriasis of the scalp.
Seasonal changes, stress, and immuno-suppression seem to affect seborrheic dermatitis.
# Treatment
There have been many strategies for the control of dandruff. Simply increasing shampooing will remove flakes.[8] However, elimination of the fungus results in dramatic improvement. Regular shampooing with an anti-fungal product can reduce recurrence.
Anti-fungal/anti-dandruff shampoos containing ketoconazole have been shown to be more effective than zinc pyrithione.[14] Ketoconazole is the most effective antifungal agent concluded by multiple studies.[15][16] | https://www.wikidoc.org/index.php/Dandruff | |
c2a9eb456958679f4c8fd21bc2cb62459e28949d | wikidoc | Database | Database
Slide set: File:Data Management.pdf
A database is a structured collection of records or data. A computer database relies upon software to organize the storage of data. The software models the database structure in what are known as database models. The model in most common use today is the relational model. Other models such as the hierarchical model and the network model use a more explicit representation of relationships (see below for explanation of the various database models).
Database management systems (DBMS) are the software used to organize and maintain the database. These are categorized according to the database model that they support. The model tends to determine the query languages that are available to access the database. A great deal of the internal engineering of a DBMS, however, is independent of the data model, and is concerned with managing factors such as performance, concurrency, integrity, and recovery from hardware failures. In these areas there are large differences between products.
# History
The earliest known use of the term data base was in November 1963, when the System Development Corporation sponsored a symposium under the title Development and Management of a Computer-centered Data Base. Database as a single word became common in Europe in the early 1970s and by the end of the decade it was being used in major American newspapers. (The abbreviation DB, however, survives.)
The first database management systems were developed in the 1960s. A pioneer in the field was Charles Bachman. Bachman's early papers show that his aim was to make more effective use of the new direct access storage devices becoming available: until then, data processing had been based on punched cards and magnetic tape, so that serial processing was the dominant activity. Two key data models arose at this time: CODASYL developed the network model based on Bachman's ideas, and (apparently independently) the hierarchical model was used in a system developed by North American Rockwell later adopted by IBM as the cornerstone of their IMS product. While IMS along with the CODASYL IDMS were the big, high visibility databases developed in the 1960s, several others were also born in that decade, some of which have a significant installed base today. Two worthy of mention are the PICK and MUMPS databases, with the former developed originally as an operating system with an embedded database and the latter as a programming language and database for the development of healthcare systems.
The relational model was proposed by E. F. Codd in 1970. He criticized existing models for confusing the abstract description of information structure with descriptions of physical access mechanisms. For a long while, however, the relational model remained of academic interest only. While CODASYL products (IDMS) and network model products (IMS) were conceived as practical engineering solutions taking account of the technology as it existed at the time, the relational model took a much more theoretical perspective, arguing (correctly) that hardware and software technology would catch up in time. Among the first implementations were Michael Stonebraker's Ingres at Berkeley, and the System R project at IBM. Both of these were research prototypes, announced during 1976. The first commercial products, Oracle and DB2, did not appear until around 1980. The first successful database product for microcomputers was dBASE for the CP/M and PC-DOS/MS-DOS operating systems.
During the 1980s, research activity focused on distributed database systems and database machines. Another important theoretical idea was the Functional Data Model, but apart from some specialized applications in genetics, molecular biology, and fraud investigation, the world took little notice.
In the 1990s, attention shifted to object-oriented databases. These had some success in fields where it was necessary to handle more complex data than relational systems could easily cope with, such as spatial databases, engineering data (including software repositories), and multimedia data. Some of these ideas were adopted by the relational vendors, who integrated new features into their products as a result. The 1990s also saw the spread of Open Source databases, such as PostgreSQL and MySQL.
In the 2000s, the fashionable area for innovation is the XML database. As with object databases, this has spawned a new collection of start-up companies, but at the same time the key ideas are being integrated into the established relational products. XML databases aim to remove the traditional divide between documents and data, allowing all of an organization's information resources to be held in one place, whether they are highly structured or not.
# Database models
Various techniques are used to model data structure. Most database systems are built around one particular data model, although it is increasingly common for products to offer support for more than one model. For any one logical model various physical implementations may be possible, and most products will offer the user some level of control in tuning the physical implementation, since the choices that are made have a significant effect on performance. Here are three examples:
## Hierarchical model
In a hierarchical model, data is organized into an inverted tree-like structure, implying a multiple downward link in each node to describe the nesting, and a sort field to keep the records in a particular order in each same-level list. This structure arranges the various data elements in a hierarchy and helps to establish logical relationships among data elements of multiple files. Each unit in the model is a record which is also known as a node. In such a model, each record on one level can be related to multiple records on the next lower level. A record that has subsidiary records is called a parent and the subsidiary records are called children. Data elements in this model are well suited for one-to-many relationships with other data elements in the database.
This model is advantageous when the data elements are inherently hierarchical. The disadvantage is that in order to prepare the database it becomes necessary to identify the requisite groups of files that are to be logically integrated. Hence, a hierarchical data model may not always be flexible enough to accommodate the dynamic needs of an organisation.
## Network model
The network model tends to store records with links to other records. Each record in the database can have multiple parents, i.e., the relationships among data elements can have a many to many relationship. Associations are tracked via "pointers". These pointers can be node numbers or disk addresses. Most network databases tend to also include some form of hierarchical model. Databases can be translated from hierarchical model to network and vice versa. The main difference between the network model and hierarchical model is that in a network model, a child can have a number of parents whereas in a hierarchical model, a child can have only one parent.
The network model provides greater advantage than the hierarchical model in that it promotes greater flexibility and data accessibility, since records at a lower level can be accessed without accessing the records above them. This model is more efficient than hierarchical model, easier to understand and can be applied to many real world problems that require routine transactions. The disadvantages are that: It is a complex process to design and develop a network database; It has to be refined frequently; It requires that the relationships among all the records be defined before development starts, and changes often demand major programming efforts; Operation and maintenance of the network model is expensive and time consuming.
Examples of database engines that have network model capabilities are RDM Embedded and RDM Server.
## Relational model
The basic data structure of the relational model is a table where information about a particular entity (say, an employee) is represented in columns and rows. The columns enumerate the various attributes of an entity (e.g. employee_name, address, phone_number). Rows (also called records) represent instances of an entity (e.g. specific employees).
The "relation" in "relational database" comes from the mathematical notion of relations from the field of set theory. A relation is a set of tuples, so rows are sometimes called tuples. All tables in a relational database adhere to three basic rules.
- The ordering of columns is immaterial
- Identical rows are not allowed in a table
- Each row has a single (separate) value for each of its columns (each tuple has an atomic value).
If the same value occurs in two different records (from the same table or different tables) it can imply a relationship between those records. Relationships between records are often categorized by their cardinality (1:1, (0), 1:M, M:M).
Tables can have a designated column or set of columns that act as a "key" to select rows from that table with the same or similar key values. A "primary key" is a key that has a unique value for each row in the table. Keys are commonly used to join or combine data from two or more tables. For example, an employee table may contain a column named address which contains a value that matches the key of a address table. Keys are also critical in the creation of indexes, which facilitate fast retrieval of data from large tables. It is not necessary to define all the keys in advance; a column can be used as a key even if it was not originally intended to be one.
### Relational operations
Users (or programs) request data from a relational database by sending it a query that is written in a special language, usually a dialect of SQL. Although SQL was originally intended for end-users, it is much more common for SQL queries to be embedded into software that provides an easier user interface. Many web applications, such as Wikipedia, perform SQL queries when generating pages.
In response to a query, the database returns a result set, which is the list of rows constituting the answer. The simplest query is just to return all the rows from a table, but more often, the rows are filtered in some way to return just the answer wanted. Often, data from multiple tables are combined into one, by doing a join. There are a number of relational operations in addition to join.
### Normal forms
Relations are classified based upon the types of anomalies to which they're vulnerable. A database that's in the first normal form is vulnerable to all types of anomalies, while a database that's in the domain/key normal form has no modification anomalies. Normal forms are hierarchical in nature. That is, the lowest level is the first normal form, and the database cannot meet the requirements for higher level normal forms without first having met all the requirements of the lesser normal form.
# Database Management Systems
## Relational database management systems
An RDBMS implements the features of the relational model outlined above. In this context, Date's Information Principle states:
The entire information content of the database is represented in one and only one way. Namely as explicit values in column positions (attributes) and rows in relations (tuples) Ergo, there are no explicit pointers between related tables.
## Post-relational database models
Several products have been identified as post-relational because the data model incorporates relations but is not constrained by the Information Principle, requiring that all information is represented by data values in relations. Products using a post-relational data model typically employ a model that actually pre-dates the relational model. These might be identified as a directed graph with trees on the nodes.
Examples of models that could be classified as post-relational are PICK aka MultiValue, and MUMPS.
## Object database models
In recent years, the object-oriented paradigm has been applied to database technology, creating a new programming model known as object databases. These databases attempt to bring the database world and the application programming world closer together, in particular by ensuring that the database uses the same type system as the application program. This aims to avoid the overhead (sometimes referred to as the impedance mismatch) of converting information between its representation in the database (for example as rows in tables) and its representation in the application program (typically as objects). At the same time, object databases attempt to introduce the key ideas of object programming, such as encapsulation and polymorphism, into the world of databases.
A variety of these ways have been tried for storing objects in a database. Some products have approached the problem from the application programming end, by making the objects manipulated by the program persistent. This also typically requires the addition of some kind of query language, since conventional programming languages do not have the ability to find objects based on their information content. Others have attacked the problem from the database end, by defining an object-oriented data model for the database, and defining a database programming language that allows full programming capabilities as well as traditional query facilities.
# DBMS internals
## Storage and physical database design
Database tables/indexes are typically stored in memory or on hard disk in one of many forms, ordered/unordered flat files, ISAM, heaps, hash buckets or B+ trees. These have various advantages and disadvantages discussed further in the main article on this topic. The most commonly used are B+ trees and ISAM.
Other important design choices relate to the clustering of data by category (such as grouping data by month, or location), creating pre-computed views known as materialized views, partitioning data by range or hash. As well memory management and storage topology can be important design choices for database designers. Just as normalization is used to reduce storage requirements and improve the extensibility of the database, conversely denormalization is often used to reduce join complexity and reduce execution time for queries.
### Indexing
All of these databases can take advantage of indexing to increase their speed. This technology has advanced tremendously since its early uses in the 1960s and 1970s. The most common kind of index is a sorted list of the contents of some particular table column, with pointers to the row associated with the value. An index allows a set of table rows matching some criterion to be located quickly. Typically, indexes are also stored in the various forms of data-structure mentioned above (such as B-trees, hashes, and linked lists). Usually, a specific technique is chosen by the database designer to increase efficiency in the particular case of the type of index required.
Relational DBMS's have the advantage that indexes can be created or dropped without changing existing applications making use of it. The database chooses between many different strategies based on which one it estimates will run the fastest. In other words, indexes are transparent to the application or end-user querying the database; while they affect performance, any SQL command will run with or without index to compute the result of an SQL statement. The RDBMS will produce a plan of how to execute the query, which is generated by analyzing the run times of the different algorithms and selecting the quickest. Some of the key algorithms that deal with joins are nested loop join, sort-merge join and hash join. Which of these is chosen depends on whether an index exists, what type it is, and its cardinality.
An index speeds up access to data, but it has disadvantages as well. First, every index increases the amount of storage on the hard drive necessary for the database file, and second, the index must be updated each time the data are altered, and this costs time.
(Thus an index saves time in the reading of data, but it costs time in entering and altering data. It thus depends on the use to which the data are to be put whether an index is on the whole a net plus or minus in the quest for efficiency.)
A special case of an index is a primary index, or primary key, which is distinguished in that the primary index must ensure a unique reference to a record. Often, for this purpose one simply uses a running index number (ID number). Primary indexes play a significant role in relational databases, and they can speed up access to data considerably.
## Transactions and concurrency
In addition to their data model, most practical databases ("transactional databases") attempt to enforce a database transaction . Ideally, the database software should enforce the ACID rules, summarized here:
- Atomicity: Either all the tasks in a transaction must be done, or none of them. The transaction must be completed, or else it must be undone (rolled back).
- Consistency: Every transaction must preserve the integrity constraints — the declared consistency rules — of the database. It cannot place the data in a contradictory state.
- Isolation: Two simultaneous transactions cannot interfere with one another. Intermediate results within a transaction are not visible to other transactions.
- Durability: Completed transactions cannot be aborted later or their results discarded. They must persist through (for instance) restarts of the DBMS after crashes
In practice, many DBMS's allow most of these rules to be selectively relaxed for better performance.
Concurrency control is a method used to ensure that transactions are executed in a safe manner and follow the ACID rules. The DBMS must be able to ensure that only serializable, recoverable schedules are allowed, and that no actions of committed transactions are lost while undoing aborted transactions .
## Replication
Replication of databases is closely related to transactions. If a database can log its individual actions, it is possible to create a duplicate of the data in real time.
The duplicate can be used to improve performance or availability of the whole database system.
Common replication concepts include:
- Master/Slave Replication: All write requests are performed on the master and then replicated to the slaves
- Quorum: The result of Read and Write requests are calculated by querying a "majority" of replicas.
- Multimaster: Two or more replicas sync each other via a transaction identifier.
Parallel synchronous replication of databases enables transactions to be replicated on multiple servers simultaneously, which provides a method for backup and security as well as data availability.
## Security
Database security denotes the system, processes, and procedures that protect a database from unintended activity.
In the United Kingdom legislation protecting the public from unauthorized disclosure of personal information held on databases falls under the Office of the Information Commissioner. United Kingdom based organizations holding personal data in electronic format (databases for example) are required to register with the Data Commissioner. (reference: )
## Locking
Locking is the act of putting a lock (access restriction) on an aspect of a database which at a particular given instance is being modified. Such locks can be applied on a row level, or on other levels such as an entire table. This helps maintain the integrity of the data by ensuring that only one user at a time can modify the data. Databases can also be locked for other reasons, like access restrictions for given levels of user.
Databases are also locked for routine database maintenance, which prevents changes being made during the maintenance. See IBM for more detail.
## Architecture
Depending on the intended use, there are a number of database architectures in use. Many databases use a combination of strategies.
On-line Transaction Processing systems (OLTP) often use a row-oriented datastore architecture, while data-warehouse and other retrieval-focused applications like Google's BigTable, or bibliographic database(library catalogue) systems may use a column-oriented datastore architecture.
Document-Oriented, XML, Knowledgebases, as well as frame databases and rdf-stores (aka Triple-Stores), may also use a combination of these architectures in their implementation.
Finally it should be noted that not all database have or need a database 'schema' (so called schema-less databases).
# Applications of databases
Databases are used in many applications, spanning virtually the entire range of computer software. Databases are the preferred method of storage for large multiuser applications, where coordination between many users is needed. Even individual users find them convenient, and many electronic mail programs and personal organizers are based on standard database technology. Software database drivers are available for most database platforms so that application software can use a common Application Programming Interface to retrieve the information stored in a database. Two commonly used database APIs are JDBC and ODBC.
For example suppliers database contains the data relating to suppliers such as;
- supplier name
- supplier code
- supplier address
It is often used by schools to teach students and grade them.
# Database as Cultural Form
Although originally a computer technology, the database, according to media theorist Lev Manovich, is becoming a new cultural form in its own right and a genre of new media. A cultural form is one of many ways that people represent the world—art and literature, for example. As contemporary culture is gradually computerized, Manovich argues, traditional cultural forms are being replaced with new ones that derive from the computer. He calls this transcoding. The database is the computer age’s key form of cultural expression, as narrative was to the modern age via cinema. In this analysis, he is using "database" metaphorically. See also database cinema.
Katherine Hayles has argued, in response, that narrative and database are not in opposition but rather are natural symbionts.
# Links to DBMS products
- 4D
- ADABAS
- Alpha Five
- Apache Derby (Java, also known as IBM Cloudscape and Sun Java DB)
- BerkeleyDB
- CouchDB
- CSQL
- Datawasp
- dBase
- FileMaker
- Firebird (database server)
- H2 (Java)
- Hsqldb (Java)
- IBM DB2
- IBM IMS (Information Management System)
- IBM UniVerse
- Informix
- Ingres
- Interbase
- InterSystems Caché
- MaxDB (formerly SapDB)
- Microsoft Access
- Microsoft SQL Server
- Model 204
- MySQL
- Nomad
- Objectivity/DB
- ObjectStore
- OpenLink Virtuoso
- OpenOffice.org Base
- Oracle Database
- Paradox (database)
- Polyhedra DBMS
- PostgreSQL
- Progress 4GL
- RDM Embedded
- ScimoreDB
- SQLite
- Superbase
- Sybase
- Teradata
- Vertica
- Visual FoxPro | Database
Slide set: File:Data Management.pdf
A database is a structured collection of records or data. A computer database relies upon software to organize the storage of data. The software models the database structure in what are known as database models. The model in most common use today is the relational model. Other models such as the hierarchical model and the network model use a more explicit representation of relationships (see below for explanation of the various database models).
Database management systems (DBMS) are the software used to organize and maintain the database. These are categorized according to the database model that they support. The model tends to determine the query languages that are available to access the database. A great deal of the internal engineering of a DBMS, however, is independent of the data model, and is concerned with managing factors such as performance, concurrency, integrity, and recovery from hardware failures. In these areas there are large differences between products.
# History
The earliest known use of the term data base was in November 1963, when the System Development Corporation sponsored a symposium under the title Development and Management of a Computer-centered Data Base[1]. Database as a single word became common in Europe in the early 1970s and by the end of the decade it was being used in major American newspapers. (The abbreviation DB, however, survives.)
The first database management systems were developed in the 1960s. A pioneer in the field was Charles Bachman. Bachman's early papers show that his aim was to make more effective use of the new direct access storage devices becoming available: until then, data processing had been based on punched cards and magnetic tape, so that serial processing was the dominant activity. Two key data models arose at this time: CODASYL developed the network model based on Bachman's ideas, and (apparently independently) the hierarchical model was used in a system developed by North American Rockwell later adopted by IBM as the cornerstone of their IMS product. While IMS along with the CODASYL IDMS were the big, high visibility databases developed in the 1960s, several others were also born in that decade, some of which have a significant installed base today. Two worthy of mention are the PICK and MUMPS databases, with the former developed originally as an operating system with an embedded database and the latter as a programming language and database for the development of healthcare systems.
The relational model was proposed by E. F. Codd in 1970. He criticized existing models for confusing the abstract description of information structure with descriptions of physical access mechanisms. For a long while, however, the relational model remained of academic interest only. While CODASYL products (IDMS) and network model products (IMS) were conceived as practical engineering solutions taking account of the technology as it existed at the time, the relational model took a much more theoretical perspective, arguing (correctly) that hardware and software technology would catch up in time. Among the first implementations were Michael Stonebraker's Ingres at Berkeley, and the System R project at IBM. Both of these were research prototypes, announced during 1976. The first commercial products, Oracle and DB2, did not appear until around 1980. The first successful database product for microcomputers was dBASE for the CP/M and PC-DOS/MS-DOS operating systems.
During the 1980s, research activity focused on distributed database systems and database machines. Another important theoretical idea was the Functional Data Model, but apart from some specialized applications in genetics, molecular biology, and fraud investigation, the world took little notice.
In the 1990s, attention shifted to object-oriented databases. These had some success in fields where it was necessary to handle more complex data than relational systems could easily cope with, such as spatial databases, engineering data (including software repositories), and multimedia data. Some of these ideas were adopted by the relational vendors, who integrated new features into their products as a result. The 1990s also saw the spread of Open Source databases, such as PostgreSQL and MySQL.
In the 2000s, the fashionable area for innovation is the XML database. As with object databases, this has spawned a new collection of start-up companies, but at the same time the key ideas are being integrated into the established relational products. XML databases aim to remove the traditional divide between documents and data, allowing all of an organization's information resources to be held in one place, whether they are highly structured or not.
# Database models
Various techniques are used to model data structure. Most database systems are built around one particular data model, although it is increasingly common for products to offer support for more than one model. For any one logical model various physical implementations may be possible, and most products will offer the user some level of control in tuning the physical implementation, since the choices that are made have a significant effect on performance. Here are three examples:
## Hierarchical model
In a hierarchical model, data is organized into an inverted tree-like structure, implying a multiple downward link in each node to describe the nesting, and a sort field to keep the records in a particular order in each same-level list. This structure arranges the various data elements in a hierarchy and helps to establish logical relationships among data elements of multiple files. Each unit in the model is a record which is also known as a node. In such a model, each record on one level can be related to multiple records on the next lower level. A record that has subsidiary records is called a parent and the subsidiary records are called children. Data elements in this model are well suited for one-to-many relationships with other data elements in the database.
This model is advantageous when the data elements are inherently hierarchical. The disadvantage is that in order to prepare the database it becomes necessary to identify the requisite groups of files that are to be logically integrated. Hence, a hierarchical data model may not always be flexible enough to accommodate the dynamic needs of an organisation.
## Network model
The network model tends to store records with links to other records. Each record in the database can have multiple parents, i.e., the relationships among data elements can have a many to many relationship. Associations are tracked via "pointers". These pointers can be node numbers or disk addresses. Most network databases tend to also include some form of hierarchical model. Databases can be translated from hierarchical model to network and vice versa. The main difference between the network model and hierarchical model is that in a network model, a child can have a number of parents whereas in a hierarchical model, a child can have only one parent.
The network model provides greater advantage than the hierarchical model in that it promotes greater flexibility and data accessibility, since records at a lower level can be accessed without accessing the records above them. This model is more efficient than hierarchical model, easier to understand and can be applied to many real world problems that require routine transactions. The disadvantages are that: It is a complex process to design and develop a network database; It has to be refined frequently; It requires that the relationships among all the records be defined before development starts, and changes often demand major programming efforts; Operation and maintenance of the network model is expensive and time consuming.
Examples of database engines that have network model capabilities are RDM Embedded and RDM Server.
## Relational model
The basic data structure of the relational model is a table where information about a particular entity (say, an employee) is represented in columns and rows. The columns enumerate the various attributes of an entity (e.g. employee_name, address, phone_number). Rows (also called records) represent instances of an entity (e.g. specific employees).
The "relation" in "relational database" comes from the mathematical notion of relations from the field of set theory. A relation is a set of tuples, so rows are sometimes called tuples. All tables in a relational database adhere to three basic rules.
- The ordering of columns is immaterial
- Identical rows are not allowed in a table
- Each row has a single (separate) value for each of its columns (each tuple has an atomic value).
If the same value occurs in two different records (from the same table or different tables) it can imply a relationship between those records. Relationships between records are often categorized by their cardinality (1:1, (0), 1:M, M:M).
Tables can have a designated column or set of columns that act as a "key" to select rows from that table with the same or similar key values. A "primary key" is a key that has a unique value for each row in the table. Keys are commonly used to join or combine data from two or more tables. For example, an employee table may contain a column named address which contains a value that matches the key of a address table. Keys are also critical in the creation of indexes, which facilitate fast retrieval of data from large tables. It is not necessary to define all the keys in advance; a column can be used as a key even if it was not originally intended to be one.
### Relational operations
Users (or programs) request data from a relational database by sending it a query that is written in a special language, usually a dialect of SQL. Although SQL was originally intended for end-users, it is much more common for SQL queries to be embedded into software that provides an easier user interface. Many web applications, such as Wikipedia, perform SQL queries when generating pages.
In response to a query, the database returns a result set, which is the list of rows constituting the answer. The simplest query is just to return all the rows from a table, but more often, the rows are filtered in some way to return just the answer wanted. Often, data from multiple tables are combined into one, by doing a join. There are a number of relational operations in addition to join.
### Normal forms
Relations are classified based upon the types of anomalies to which they're vulnerable. A database that's in the first normal form is vulnerable to all types of anomalies, while a database that's in the domain/key normal form has no modification anomalies. Normal forms are hierarchical in nature. That is, the lowest level is the first normal form, and the database cannot meet the requirements for higher level normal forms without first having met all the requirements of the lesser normal form.
# Database Management Systems
## Relational database management systems
An RDBMS implements the features of the relational model outlined above. In this context, Date's Information Principle states:
The entire information content of the database is represented in one and only one way. Namely as explicit values in column positions (attributes) and rows in relations (tuples) Ergo, there are no explicit pointers between related tables.
## Post-relational database models
Several products have been identified as post-relational because the data model incorporates relations but is not constrained by the Information Principle, requiring that all information is represented by data values in relations. Products using a post-relational data model typically employ a model that actually pre-dates the relational model. These might be identified as a directed graph with trees on the nodes.
Examples of models that could be classified as post-relational are PICK aka MultiValue, and MUMPS.
## Object database models
In recent years, the object-oriented paradigm has been applied to database technology, creating a new programming model known as object databases. These databases attempt to bring the database world and the application programming world closer together, in particular by ensuring that the database uses the same type system as the application program. This aims to avoid the overhead (sometimes referred to as the impedance mismatch) of converting information between its representation in the database (for example as rows in tables) and its representation in the application program (typically as objects). At the same time, object databases attempt to introduce the key ideas of object programming, such as encapsulation and polymorphism, into the world of databases.
A variety of these ways have been tried for storing objects in a database. Some products have approached the problem from the application programming end, by making the objects manipulated by the program persistent. This also typically requires the addition of some kind of query language, since conventional programming languages do not have the ability to find objects based on their information content. Others have attacked the problem from the database end, by defining an object-oriented data model for the database, and defining a database programming language that allows full programming capabilities as well as traditional query facilities.
# DBMS internals
## Storage and physical database design
Template:Expand-section
Database tables/indexes are typically stored in memory or on hard disk in one of many forms, ordered/unordered flat files, ISAM, heaps, hash buckets or B+ trees. These have various advantages and disadvantages discussed further in the main article on this topic. The most commonly used are B+ trees and ISAM.
Other important design choices relate to the clustering of data by category (such as grouping data by month, or location), creating pre-computed views known as materialized views, partitioning data by range or hash. As well memory management and storage topology can be important design choices for database designers. Just as normalization is used to reduce storage requirements and improve the extensibility of the database, conversely denormalization is often used to reduce join complexity and reduce execution time for queries. [2]
### Indexing
All of these databases can take advantage of indexing to increase their speed. This technology has advanced tremendously since its early uses in the 1960s and 1970s. The most common kind of index is a sorted list of the contents of some particular table column, with pointers to the row associated with the value. An index allows a set of table rows matching some criterion to be located quickly. Typically, indexes are also stored in the various forms of data-structure mentioned above (such as B-trees, hashes, and linked lists). Usually, a specific technique is chosen by the database designer to increase efficiency in the particular case of the type of index required.
Relational DBMS's have the advantage that indexes can be created or dropped without changing existing applications making use of it. The database chooses between many different strategies based on which one it estimates will run the fastest. In other words, indexes are transparent to the application or end-user querying the database; while they affect performance, any SQL command will run with or without index to compute the result of an SQL statement. The RDBMS will produce a plan of how to execute the query, which is generated by analyzing the run times of the different algorithms and selecting the quickest. Some of the key algorithms that deal with joins are nested loop join, sort-merge join and hash join. Which of these is chosen depends on whether an index exists, what type it is, and its cardinality.
An index speeds up access to data, but it has disadvantages as well. First, every index increases the amount of storage on the hard drive necessary for the database file, and second, the index must be updated each time the data are altered, and this costs time.
(Thus an index saves time in the reading of data, but it costs time in entering and altering data. It thus depends on the use to which the data are to be put whether an index is on the whole a net plus or minus in the quest for efficiency.)
A special case of an index is a primary index, or primary key, which is distinguished in that the primary index must ensure a unique reference to a record. Often, for this purpose one simply uses a running index number (ID number). Primary indexes play a significant role in relational databases, and they can speed up access to data considerably.
## Transactions and concurrency
In addition to their data model, most practical databases ("transactional databases") attempt to enforce a database transaction . Ideally, the database software should enforce the ACID rules, summarized here:
- Atomicity: Either all the tasks in a transaction must be done, or none of them. The transaction must be completed, or else it must be undone (rolled back).
- Consistency: Every transaction must preserve the integrity constraints — the declared consistency rules — of the database. It cannot place the data in a contradictory state.
- Isolation: Two simultaneous transactions cannot interfere with one another. Intermediate results within a transaction are not visible to other transactions.
- Durability: Completed transactions cannot be aborted later or their results discarded. They must persist through (for instance) restarts of the DBMS after crashes
In practice, many DBMS's allow most of these rules to be selectively relaxed for better performance.
Concurrency control is a method used to ensure that transactions are executed in a safe manner and follow the ACID rules. The DBMS must be able to ensure that only serializable, recoverable schedules are allowed, and that no actions of committed transactions are lost while undoing aborted transactions .
## Replication
Replication of databases is closely related to transactions. If a database can log its individual actions, it is possible to create a duplicate of the data in real time.
The duplicate can be used to improve performance or availability of the whole database system.
Common replication concepts include:
- Master/Slave Replication: All write requests are performed on the master and then replicated to the slaves
- Quorum: The result of Read and Write requests are calculated by querying a "majority" of replicas.
- Multimaster: Two or more replicas sync each other via a transaction identifier.
Parallel synchronous replication of databases enables transactions to be replicated on multiple servers simultaneously, which provides a method for backup and security as well as data availability.
## Security
Database security denotes the system, processes, and procedures that protect a database from unintended activity.
In the United Kingdom legislation protecting the public from unauthorized disclosure of personal information held on databases falls under the Office of the Information Commissioner. United Kingdom based organizations holding personal data in electronic format (databases for example) are required to register with the Data Commissioner. (reference: [1])
## Locking
Template:Expand-section
Locking is the act of putting a lock (access restriction) on an aspect of a database which at a particular given instance is being modified. Such locks can be applied on a row level, or on other levels such as an entire table. This helps maintain the integrity of the data by ensuring that only one user at a time can modify the data. Databases can also be locked for other reasons, like access restrictions for given levels of user.
Databases are also locked for routine database maintenance, which prevents changes being made during the maintenance. See IBM for more detail.
## Architecture
Depending on the intended use, there are a number of database architectures in use. Many databases use a combination of strategies.
On-line Transaction Processing systems (OLTP) often use a row-oriented datastore architecture, while data-warehouse and other retrieval-focused applications like Google's BigTable, or bibliographic database(library catalogue) systems may use a column-oriented datastore architecture.
Document-Oriented, XML, Knowledgebases, as well as frame databases and rdf-stores (aka Triple-Stores), may also use a combination of these architectures in their implementation.
Finally it should be noted that not all database have or need a database 'schema' (so called schema-less databases).
# Applications of databases
Databases are used in many applications, spanning virtually the entire range of computer software. Databases are the preferred method of storage for large multiuser applications, where coordination between many users is needed. Even individual users find them convenient, and many electronic mail programs and personal organizers are based on standard database technology. Software database drivers are available for most database platforms so that application software can use a common Application Programming Interface to retrieve the information stored in a database. Two commonly used database APIs are JDBC and ODBC.
For example suppliers database contains the data relating to suppliers such as;
- supplier name
- supplier code
- supplier address
It is often used by schools to teach students and grade them.
# Database as Cultural Form
Although originally a computer technology, the database, according to media theorist Lev Manovich, is becoming a new cultural form in its own right and a genre of new media[3][4]. A cultural form is one of many ways that people represent the world—art and literature, for example. As contemporary culture is gradually computerized, Manovich argues, traditional cultural forms are being replaced with new ones that derive from the computer. He calls this transcoding. The database is the computer age’s key form of cultural expression, as narrative was to the modern age via cinema. In this analysis, he is using "database" metaphorically. See also database cinema.
Katherine Hayles has argued, in response, that narrative and database are not in opposition but rather are natural symbionts. [5]
# Links to DBMS products
- 4D
- ADABAS
- Alpha Five
- Apache Derby (Java, also known as IBM Cloudscape and Sun Java DB)
- BerkeleyDB
- CouchDB
- CSQL
- Datawasp
- dBase
- FileMaker
- Firebird (database server)
- H2 (Java)
- Hsqldb (Java)
- IBM DB2
- IBM IMS (Information Management System)
- IBM UniVerse
- Informix
- Ingres
- Interbase
- InterSystems Caché
- MaxDB (formerly SapDB)
- Microsoft Access
- Microsoft SQL Server
- Model 204
- MySQL
- Nomad
- Objectivity/DB
- ObjectStore
- OpenLink Virtuoso
- OpenOffice.org Base
- Oracle Database
- Paradox (database)
- Polyhedra DBMS
- PostgreSQL
- Progress 4GL
- RDM Embedded
- ScimoreDB
- SQLite
- Superbase
- Sybase
- Teradata
- Vertica
- Visual FoxPro | https://www.wikidoc.org/index.php/Database | |
32a070e1c81e715642d1b512464c19003c8a62ae | wikidoc | Delusion | Delusion
# Overview
A delusion is commonly defined as a fixed false belief and is used in everyday language to describe a belief that is either false, fanciful or derived from deception. In psychiatry, the definition is necessarily more precise and implies that the belief is pathological (the result of an illness or illness process). As a pathology it is distinct from a belief based on false or incomplete information or certain effects of perception which would more properly be termed an apperception or illusion.
Delusions typically occur in the context of neurological or mental illness, although they are not tied to any particular disease and have been found to occur in the context of many pathological states (both physical and mental). However, they are of particular diagnostic importance in psychotic disorders and particularly in schizophrenia.
# Psychiatric definition
Although non-specific concepts of madness have been around for several thousand years, the psychiatrist and philosopher Karl Jaspers was the first to define the three main criteria for a belief to be considered delusional in his book General Psychopathology. These criteria are:
- certainty (held with absolute conviction)
- incorrigibility (not changeable by compelling counterargument or proof to the contrary)
- impossibility or falsity of content (implausible, bizarre or patently untrue)
These criteria still live on in modern psychiatric diagnosis. In the most recent Diagnostic and Statistical Manual of Mental Disorders, a delusion is defined as:
Example: Nebraska Head Coach Bill Callahan ]
# Causes
## Common Causes
- Alzheimer's Disease
- Chronic psychostimulant and alcohol abuse
- Delusional disorder
- Dementia
- Myxedema madness
- Illicit drugs
- Mania or hypomania
- Psychotic depression
- Schizoaffective disorder
- Schizophrenia
## Causes by Organ System
## Causes in Alphabetical Order
# Diagnostic issues
The modern definition and Jaspers' original criteria have been criticised, as counter-examples can be shown for every defining feature.
Studies on psychiatric patients have shown that delusions can be seen to vary in intensity and conviction over time which suggests that certainty and incorrigibility are not necessary components of a delusional belief.
Delusions do not necessarily have to be false or 'incorrect inferences about external reality'. Some religious or spiritual beliefs (such as 'I believe in the existence of God') by their nature may not be falsifiable, and hence cannot be described as false or incorrect, no matter whether the person holding these beliefs was diagnosed as delusional or not.
In other situations the delusion may turn out to be true belief. For example, delusional jealousy, where a person believes that their partner is being unfaithful (and may even follow them into the bathroom believing them to be seeing their lover even during the briefest of partings) may result in the faithful partner being driven to infidelity by the constant and unreasonable strain put on them by their delusional spouse. In this case the delusion does not cease to be a delusion because the content later turns out to be true.
In other cases, the delusion may be assumed to be false by a doctor or psychiatrist assessing the belief, because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a person’s claims leading to some true beliefs to be erroneously classified as delusional. This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).
Similar factors have led to criticisms of Jaspers' definition of true delusions as being ultimately 'un-understandable'. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information which might make a belief otherwise interpretable.
Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. Similarly, Thomas Kuhn argued in The Structure of Scientific Revolutions that scientists can hold strong beliefs in scientific theories despite considerable apparent discrepancies with experimental evidence.
These factors have led the psychiatrist Anthony David to note that "there is no acceptable (rather than accepted) definition of a delusion". In practice psychiatrists tend to diagnose a belief as delusional if it is either patently bizarre, causing significant distress, or excessively pre-occupies the patient, especially if the person is subsequently unswayed in belief by counter-evidence or reasonable arguments.
# Related Chapters
- Delirium
- Capgras delusion
- Clinical lycanthropy
- Cotard delusion
- Delusional disorder
- Delusional jealousy
- Delusional misidentification syndrome
- Delusional parasitosis
- Erotomania
- Folie à deux
- Fregoli delusion
- Grandiose delusion
- Illusion
- Karl Jaspers
- Jerusalem syndrome
- R. D. Laing
- Reduplicative paramnesia
- Martha Mitchell effect
- Monothematic delusions
- Paranoia
- Paranoia Network
- Psychosis
- Schizophrenia
# Further reading
- Bell, V., Halligan, P.W. & Ellis, H. (2003) Beliefs about delusions. The Psychologist, 16(8), 418-423. Full text
- Blackwood NJ, Howard RJ, Bentall RP, Murray RM. (2001) Cognitive neuropsychiatric models of persecutory delusions. American Journal of Psychiatry, 158 (4), 527-39. Full text
- Coltheart, M. & Davies, M. (2000) (Eds.) Pathologies of belief. Oxford: Blackwell. ISBN 0-631-22136-0
- Persaud, R. (2003) From the Edge of the Couch: Bizarre Psychiatric Cases and What They Teach Us About Ourselves. Bantam. ISBN 0-553-81346-3. | Delusion
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A delusion is commonly defined as a fixed false belief and is used in everyday language to describe a belief that is either false, fanciful or derived from deception. In psychiatry, the definition is necessarily more precise and implies that the belief is pathological (the result of an illness or illness process). As a pathology it is distinct from a belief based on false or incomplete information or certain effects of perception which would more properly be termed an apperception or illusion.
Delusions typically occur in the context of neurological or mental illness, although they are not tied to any particular disease and have been found to occur in the context of many pathological states (both physical and mental). However, they are of particular diagnostic importance in psychotic disorders and particularly in schizophrenia.
# Psychiatric definition
Although non-specific concepts of madness have been around for several thousand years, the psychiatrist and philosopher Karl Jaspers was the first to define the three main criteria for a belief to be considered delusional in his book General Psychopathology. These criteria are:
- certainty (held with absolute conviction)
- incorrigibility (not changeable by compelling counterargument or proof to the contrary)
- impossibility or falsity of content (implausible, bizarre or patently untrue)
These criteria still live on in modern psychiatric diagnosis. In the most recent Diagnostic and Statistical Manual of Mental Disorders, a delusion is defined as:
Example: Nebraska Head Coach Bill Callahan [[2]]
# Causes
## Common Causes
- Alzheimer's Disease
- Chronic psychostimulant and alcohol abuse
- Delusional disorder
- Dementia
- Myxedema madness
- Illicit drugs
- Mania or hypomania
- Psychotic depression
- Schizoaffective disorder
- Schizophrenia
## Causes by Organ System
## Causes in Alphabetical Order
# Diagnostic issues
The modern definition and Jaspers' original criteria have been criticised, as counter-examples can be shown for every defining feature.
Studies on psychiatric patients have shown that delusions can be seen to vary in intensity and conviction over time which suggests that certainty and incorrigibility are not necessary components of a delusional belief.[1]
Delusions do not necessarily have to be false or 'incorrect inferences about external reality'.[2] Some religious or spiritual beliefs (such as 'I believe in the existence of God') by their nature may not be falsifiable, and hence cannot be described as false or incorrect, no matter whether the person holding these beliefs was diagnosed as delusional or not. [3]
In other situations the delusion may turn out to be true belief.[4] For example, delusional jealousy, where a person believes that their partner is being unfaithful (and may even follow them into the bathroom believing them to be seeing their lover even during the briefest of partings) may result in the faithful partner being driven to infidelity by the constant and unreasonable strain put on them by their delusional spouse. In this case the delusion does not cease to be a delusion because the content later turns out to be true.
In other cases, the delusion may be assumed to be false by a doctor or psychiatrist assessing the belief, because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a person’s claims leading to some true beliefs to be erroneously classified as delusional.[5] This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).
Similar factors have led to criticisms of Jaspers' definition of true delusions as being ultimately 'un-understandable'. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information which might make a belief otherwise interpretable.
Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. Similarly, Thomas Kuhn argued in The Structure of Scientific Revolutions that scientists can hold strong beliefs in scientific theories despite considerable apparent discrepancies with experimental evidence.[6]
These factors have led the psychiatrist Anthony David to note that "there is no acceptable (rather than accepted) definition of a delusion".[7] In practice psychiatrists tend to diagnose a belief as delusional if it is either patently bizarre, causing significant distress, or excessively pre-occupies the patient, especially if the person is subsequently unswayed in belief by counter-evidence or reasonable arguments.
# Related Chapters
- Delirium
- Capgras delusion
- Clinical lycanthropy
- Cotard delusion
- Delusional disorder
- Delusional jealousy
- Delusional misidentification syndrome
- Delusional parasitosis
- Erotomania
- Folie à deux
- Fregoli delusion
- Grandiose delusion
- Illusion
- Karl Jaspers
- Jerusalem syndrome
- R. D. Laing
- Reduplicative paramnesia
- Martha Mitchell effect
- Monothematic delusions
- Paranoia
- Paranoia Network
- Psychosis
- Schizophrenia
# Further reading
- Bell, V., Halligan, P.W. & Ellis, H. (2003) Beliefs about delusions. The Psychologist, 16(8), 418-423. Full text
- Blackwood NJ, Howard RJ, Bentall RP, Murray RM. (2001) Cognitive neuropsychiatric models of persecutory delusions. American Journal of Psychiatry, 158 (4), 527-39. Full text
- Coltheart, M. & Davies, M. (2000) (Eds.) Pathologies of belief. Oxford: Blackwell. ISBN 0-631-22136-0
- Persaud, R. (2003) From the Edge of the Couch: Bizarre Psychiatric Cases and What They Teach Us About Ourselves. Bantam. ISBN 0-553-81346-3. | https://www.wikidoc.org/index.php/Ddx:Delusions | |
338126920749585ea30a8de323df90baa5addc11 | wikidoc | Ferritin | Ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including algae, bacteria, higher plants, and animals. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. Plasma ferritin is also an indirect marker of the total amount of iron stored in the body, hence serum ferritin is used as a diagnostic test for iron-deficiency anemia.
Ferritin is a globular protein complex consisting of 24 protein subunits forming a nanocage with multiple metal–protein interactions. It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin.
# Gene
Ferritin genes are highly conserved between species. All vertebrate ferritin genes have three introns and four exons. In human ferritin, introns are present between amino acid residues 14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred untranslated bases at either end of the combined exons. The tyrosine residue at amino acid position 27 is thought to be associated with biomineralization.
# Protein structure
Ferritin is a hollow globular protein of 474 kDa consisting of 24 subunits that is present in every cell type. Typically it has internal and external diameters of about 8 and 12 nm, respectively. In vertebrates, these subunits are both the light (L) and the heavy (H) type with an apparent molecular weight of 19 kDa or 21 kDa respectively; their sequences are homologous (about 50% identical). Amphibians have an additional ("M") type of ferritin; the single ferritin of plants and bacteria most closely resembles the vertebrate H-type. Two types have been recovered in the gastropod Lymnaea, the somatic ferritin being distinct from the yolk ferritin (see below). An additional subunit resembling Lymnaea soma ferritin is associated with shell formation in the pearl oyster. Two types are present in the parasite Schistosoma, one in males, the other in females. All the aforementioned ferritins are similar, in terms of their primary sequence, with the vertebrate H-type. In E. coli, a 20% similarity to human H-ferritin is observed. Inside the ferritin shell, iron ions form crystallites together with phosphate and hydroxide ions. The resulting particle is similar to the mineral ferrihydrite. Each ferritin complex can store about 4500 iron (Fe3+) ions.
Some ferritin complexes in vertebrates are hetero-oligomers of two highly related gene products with slightly different physiological properties. The ratio of the two homologous proteins in the complex depends on the relative expression levels of the two genes.
Mitochondrial ferritin was recently identified as a protein precursor, and is classified as a metal-binding protein that is located within the mitochondria. After the protein is taken up by the mitochondria it can be processed into a mature protein and assemble to form functional ferritin shells. Its structure was determined at 1.70 angstroms through the use of X-ray diffraction and contains 182 residues. It is 67% helical. The Ramachandran plot shows that the structure of mitochondrial ferritin is mainly alpha helical with a low prevalence of beta sheets. Unlike other human ferritin, it appears to have no introns in its genetic code.
# Function
## Iron storage
Ferritin serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required. The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of mRNA. mRNA concentration is further tweaked by changes to how it is stored and how efficiently it is transcribed. The presence of iron itself is a major trigger for the production of ferritin, with some exceptions (such as the yolk ferritin of the gastropod Lymnaea, which lacks an iron-responsive unit).
Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton reaction. Hence vertebrates evolve an elaborate set of protective mechanisms to bind iron in various tissue compartments. Within cells, iron is stored in a protein complex as ferritin or hemosiderin. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the reticuloendothelial system, protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells although hemosiderin is less readily available. Under steady state conditions, the serum ferritin level correlates with total body iron stores; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.
Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as molluscs to control the concentration and distribution of iron, thus sculpting shell morphology and colouration. It also plays a role in the haemolymph of the polyplacophora where it serves to rapidly transport iron to the mineralizing radula.
Iron is released from ferritin for use by ferritin degradation, which is performed mainly by lysosomes.
## Ferroxidase activity
Vertebrate ferritin consists of two or three subunits which are named based on their molecular weight: L "light", H "heavy", and M "middle" subunits. The M subunit has only been reported in bullfrogs. In bacteria and archaea, ferritin consists of one subunit type. H and M subunits of eukaryotic ferritin and all subunits of bacterial and archaeal ferritin are H-type and have ferroxidase activity, which is the conversion of iron from the ferrous (Fe2+) to ferric (Fe3+) forms. This limits the deleterious reaction which occurs between ferrous iron and hydrogen peroxide known as the Fenton reaction which produces the highly damaging hydroxyl radical. The ferroxidase activity occurs at a diiron binding site in the middle of each H-type subunits. After oxidation of Fe(II), the Fe(III) product stays metastably in the ferroxidase center and is displaced by Fe(II), a mechanism that appears to be common among ferritins of all three kingdoms of life. The light chain of ferritin has no ferroxidase activity but may be responsible for the electron transfer across the protein cage.
## Immune response
Ferritin concentrations increase drastically in the presence of an infection or cancer. Endotoxins are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as Pseudomonas, although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism.
## Stress response
The concentration of ferritin has been shown to increase in response to stresses such as anoxia; this implies that it is an acute phase protein.
## Mitochondria
Mitochondrial ferritin has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.
## Yolk
In some snails, the protein component of the egg yolk is primarily ferritin; this is a different ferritin, with a different genetic sequence, from the somatic ferritin. It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs.
## Industrial applications
Ferritin is also used in materials science as a precursor in making iron nanoparticles for carbon nanotube growth by chemical vapor deposition.
# Tissue distribution
In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma.
# Diagnostic uses
Serum ferritin levels are measured in medical laboratories as part of the iron studies workup for iron-deficiency anemia. The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of anemia of chronic disease where ferritin is elevated in its capacity as an inflammatory acute phase protein and not as a marker for iron overload.
## Normal ranges
A normal ferritin blood level, referred to as the reference interval is determined by many testing laboratories. The ranges for ferritin can vary between laboratories but typical ranges would be between 30–300 ng/mL (=μg/L) for males, and 18–160 ng/mL (=μg/L) for females.
## Deficiency
If the ferritin level is low, there is a risk for lack of iron, which could lead to anemia.
In the setting of anemia, low serum ferritin is the most specific lab test for iron-deficiency anemia. However it is less sensitive, since its levels are increased in the blood by infection or any type of chronic inflammation, and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range.
Low ferritin may also indicate hypothyroidism, vitamin C deficiency or celiac disease.
Low serum ferritin levels are seen in some patients with restless legs syndrome, not necessarily related to anemia, but perhaps due to low iron stores short of anemia.
A falsely low blood ferritin (equivalent to a false positive test) is very uncommon, but can result from a hook effect of the measuring tools in extreme cases.
Vegetarianism may cause low serum ferritin levels, resulting from iron deficiency, with one study finding this in 19% of vegetarians.
## Excess
If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload.
Ferritin is also used as a marker for iron overload disorders, such as hemochromatosis or hemosiderosis. Adult-onset Still's disease, some porphyrias, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome are diseases in which the ferritin level may be abnormally raised.
As ferritin is also an acute-phase reactant, it is often elevated in the course of disease. A normal C-reactive protein can be used to exclude elevated ferritin caused by acute phase reactions.
According to a study of anorexia nervosa patients, ferritin can be elevated during periods of acute malnourishment, perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls.
Another study suggests that due to the catabolic nature of anorexia nervosa, isoferritins may be released. Furthermore, ferritin has significant non storage roles within the body, such as protection from oxidative damage. The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through immunoassay or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status.
# Applications
Cavities formed by ferritin and mini-ferritins (Dps) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles (NPs). Protein shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications. | Ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including algae, bacteria, higher plants, and animals. In humans, it acts as a buffer against iron deficiency and iron overload.[3] Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. Plasma ferritin is also an indirect marker of the total amount of iron stored in the body, hence serum ferritin is used as a diagnostic test for iron-deficiency anemia.[4]
Ferritin is a globular protein complex consisting of 24 protein subunits forming a nanocage with multiple metal–protein interactions.[5] It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin.
# Gene
Ferritin genes are highly conserved between species. All vertebrate ferritin genes have three introns and four exons.[6] In human ferritin, introns are present between amino acid residues 14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred untranslated bases at either end of the combined exons.[7] The tyrosine residue at amino acid position 27 is thought to be associated with biomineralization.[8]
# Protein structure
Ferritin is a hollow globular protein of 474 kDa consisting of 24 subunits that is present in every cell type.[7] Typically it has internal and external diameters of about 8 and 12 nm, respectively.[9] In vertebrates, these subunits are both the light (L) and the heavy (H) type with an apparent molecular weight of 19 kDa or 21 kDa respectively; their sequences are homologous (about 50% identical).[7] Amphibians have an additional ("M") type of ferritin;[10] the single ferritin of plants and bacteria most closely resembles the vertebrate H-type.[10] Two types have been recovered in the gastropod Lymnaea, the somatic ferritin being distinct from the yolk ferritin (see below).[10] An additional subunit resembling Lymnaea soma ferritin is associated with shell formation in the pearl oyster.[11] Two types are present in the parasite Schistosoma, one in males, the other in females.[10] All the aforementioned ferritins are similar, in terms of their primary sequence, with the vertebrate H-type.[10] In E. coli, a 20% similarity to human H-ferritin is observed.[10] Inside the ferritin shell, iron ions form crystallites together with phosphate and hydroxide ions. The resulting particle is similar to the mineral ferrihydrite. Each ferritin complex can store about 4500 iron (Fe3+) ions.[7][10]
Some ferritin complexes in vertebrates are hetero-oligomers of two highly related gene products with slightly different physiological properties. The ratio of the two homologous proteins in the complex depends on the relative expression levels of the two genes.
Mitochondrial ferritin was recently identified as a protein precursor, and is classified as a metal-binding protein that is located within the mitochondria.[12] After the protein is taken up by the mitochondria it can be processed into a mature protein and assemble to form functional ferritin shells. Its structure was determined at 1.70 angstroms through the use of X-ray diffraction and contains 182 residues. It is 67% helical. The Ramachandran plot[13] shows that the structure of mitochondrial ferritin is mainly alpha helical with a low prevalence of beta sheets. Unlike other human ferritin, it appears to have no introns in its genetic code.
# Function
## Iron storage
Ferritin serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required.[14] The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of mRNA. mRNA concentration is further tweaked by changes to how it is stored and how efficiently it is transcribed.[7] The presence of iron itself is a major trigger for the production of ferritin,[7] with some exceptions (such as the yolk ferritin of the gastropod Lymnaea, which lacks an iron-responsive unit).[10]
Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton reaction.[15] Hence vertebrates evolve an elaborate set of protective mechanisms to bind iron in various tissue compartments[discuss]. Within cells, iron is stored in a protein complex as ferritin or hemosiderin. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the reticuloendothelial system, protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells although hemosiderin is less readily available. Under steady state conditions, the serum ferritin level correlates with total body iron stores; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.
Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as molluscs to control the concentration and distribution of iron, thus sculpting shell morphology and colouration.[16][17] It also plays a role in the haemolymph of the polyplacophora where it serves to rapidly transport iron to the mineralizing radula.[18]
Iron is released from ferritin for use by ferritin degradation, which is performed mainly by lysosomes.[19]
## Ferroxidase activity
Vertebrate ferritin consists of two or three subunits which are named based on their molecular weight: L "light", H "heavy", and M "middle" subunits. The M subunit has only been reported in bullfrogs. In bacteria and archaea, ferritin consists of one subunit type.[20] H and M subunits of eukaryotic ferritin and all subunits of bacterial and archaeal ferritin are H-type and have ferroxidase activity, which is the conversion of iron from the ferrous (Fe2+) to ferric (Fe3+) forms. This limits the deleterious reaction which occurs between ferrous iron and hydrogen peroxide known as the Fenton reaction which produces the highly damaging hydroxyl radical. The ferroxidase activity occurs at a diiron binding site in the middle of each H-type subunits.[20][21] After oxidation of Fe(II), the Fe(III) product stays metastably in the ferroxidase center and is displaced by Fe(II),[21][22] a mechanism that appears to be common among ferritins of all three kingdoms of life.[20] The light chain of ferritin has no ferroxidase activity but may be responsible for the electron transfer across the protein cage.[23]
## Immune response
Ferritin concentrations increase drastically in the presence of an infection or cancer. Endotoxins are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as Pseudomonas, although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism.[24]
## Stress response
The concentration of ferritin has been shown to increase in response to stresses such as anoxia;[25] this implies that it is an acute phase protein.[26]
## Mitochondria
Mitochondrial ferritin has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.
## Yolk
In some snails, the protein component of the egg yolk is primarily ferritin;[27] this is a different ferritin, with a different genetic sequence, from the somatic ferritin. It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs.[27]
## Industrial applications
Ferritin is also used in materials science as a precursor in making iron nanoparticles for carbon nanotube growth by chemical vapor deposition.
# Tissue distribution
In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma.[24]
# Diagnostic uses
Serum ferritin levels are measured in medical laboratories as part of the iron studies workup for iron-deficiency anemia.[5] The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of anemia of chronic disease where ferritin is elevated in its capacity as an inflammatory acute phase protein and not as a marker for iron overload.
## Normal ranges
A normal ferritin blood level, referred to as the reference interval is determined by many testing laboratories. The ranges for ferritin can vary between laboratories but typical ranges would be between 30–300 ng/mL (=μg/L) for males, and 18–160 ng/mL (=μg/L) for females.
## Deficiency
If the ferritin level is low, there is a risk for lack of iron, which could lead to anemia.
In the setting of anemia, low serum ferritin is the most specific lab test for iron-deficiency anemia.[29] However it is less sensitive, since its levels are increased in the blood by infection or any type of chronic inflammation,[30] and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range.
Low ferritin may also indicate hypothyroidism, vitamin C deficiency or celiac disease.
Low serum ferritin levels are seen in some patients with restless legs syndrome, not necessarily related to anemia, but perhaps due to low iron stores short of anemia.[31][32]
A falsely low blood ferritin (equivalent to a false positive test) is very uncommon,[30] but can result from a hook effect of the measuring tools in extreme cases.[33]
Vegetarianism may cause low serum ferritin levels, resulting from iron deficiency, with one study finding this in 19% of vegetarians.[34]
## Excess
If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload.
Ferritin is also used as a marker for iron overload disorders, such as hemochromatosis or hemosiderosis. Adult-onset Still's disease, some porphyrias, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome are diseases in which the ferritin level may be abnormally raised.
As ferritin is also an acute-phase reactant, it is often elevated in the course of disease. A normal C-reactive protein can be used to exclude elevated ferritin caused by acute phase reactions.[citation needed]
According to a study of anorexia nervosa patients, ferritin can be elevated during periods of acute malnourishment, perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls.[35]
Another study suggests that due to the catabolic nature of anorexia nervosa, isoferritins may be released. Furthermore, ferritin has significant non storage roles within the body, such as protection from oxidative damage. The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through immunoassay or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status.[36]
# Applications
Cavities formed by ferritin and mini-ferritins (Dps) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles (NPs).[37][38][39][40] Protein shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications.[5] | https://www.wikidoc.org/index.php/Ddx:Ferritin | |
99b08d9515e73ced7441bbb9e67821ea54902ca5 | wikidoc | Flushing | Flushing
# Overview
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face or cheeks, and generally assumed to reflect embarrassment. Flushing is also a cardinal symptom of carcinoid syndrome – the syndrome that results from hormones (often serotonin or histamine) being secreted into systemic circulation.
# Causes
## Causes by Organ System
## Causes in Alphabetical Order
# Sex flush
Commonly referred to as the sex flush, vasocongestion (increased blood flow) of the skin can occur during all four phases of the human sexual response cycle. Studies show that the sex flush occurs in approximately 50-75% of females and 25% of males, yet not consistently. The sex flush tends to occur more often under warmer conditions and may not appear at all under cooler temperatures. It has also been commonly observed that the marked degree of the sex flush can predict the intensity of orgasm to follow.
During the female sex flush, pinkish spots develop under the breasts, then spread to the breasts, torso, face, hands, soles of the feet, and possibly over the entire body. Vasocongestion is also responsible for the darkening of the clitoris and the walls of the vagina during sexual arousal. During the male sex flush, the coloration of the skin develops less consistently than in the female, but typically starts with the epigastrium (upper abdomen), spreads across the chest, then continues to the neck, face, forehead, back, and sometimes, shoulders and forearms.
The sex flush typically disappears soon after orgasm occurs, but this may take up to two hours or so, and sometimes, intense sweating will occur simultaneously. The flush usually diminishes in reverse of which it appeared. | Flushing
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face or cheeks, and generally assumed to reflect embarrassment. Flushing is also a cardinal symptom of carcinoid syndrome – the syndrome that results from hormones (often serotonin or histamine) being secreted into systemic circulation.
# Causes
## Causes by Organ System
## Causes in Alphabetical Order
# Sex flush
Commonly referred to as the sex flush, vasocongestion (increased blood flow) of the skin can occur during all four phases of the human sexual response cycle. Studies show that the sex flush occurs in approximately 50-75% of females and 25% of males, yet not consistently. The sex flush tends to occur more often under warmer conditions and may not appear at all under cooler temperatures. It has also been commonly observed that the marked degree of the sex flush can predict the intensity of orgasm to follow.
During the female sex flush, pinkish spots develop under the breasts, then spread to the breasts, torso, face, hands, soles of the feet, and possibly over the entire body. Vasocongestion is also responsible for the darkening of the clitoris and the walls of the vagina during sexual arousal. During the male sex flush, the coloration of the skin develops less consistently than in the female, but typically starts with the epigastrium (upper abdomen), spreads across the chest, then continues to the neck, face, forehead, back, and sometimes, shoulders and forearms.
The sex flush typically disappears soon after orgasm occurs, but this may take up to two hours or so, and sometimes, intense sweating will occur simultaneously. The flush usually diminishes in reverse of which it appeared. | https://www.wikidoc.org/index.php/Ddx:Flushing | |
f3553c6dcb2bf2cdc2b8bd2f9159645b1bac300f | wikidoc | Myopathy | Myopathy
# Overview
In medicine, a myopathy is a neuromuscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease (myo- Greek μυσ "muscle" + pathy Greek "suffering"). This meaning implies that the primary defect is within the muscle, as opposed to the nerves ("neuropathies" or "neurogenic" disorders) or elsewhere (e.g., the brain etc.). Muscle cramps, stiffness, and spasm can also be associated with myopathy.
# Classes
Because myopathy is such a general term, there are several classes of myopathy.... (ICD-10 codes are provided where available.)
- (G71.0) Dystrophies (or muscular dystrophies) are a subgroup of myopathies characterized by muscle degeneration and regeneration. Clinically, muscular dystrophies are typically progressive, because the muscles' ability to regenerate is eventually lost, leading to progressive weakness, often leading to use of a wheelchair, and eventually death, usually related to respiratory weakness.
- (G71.1) Myotonia
Neuromyotonia
- Neuromyotonia
- (G71.2) The congenital myopathies do not show evidence for either a progressive dystrophic process (i.e., muscle death) or inflammation, but instead characteristic microscopic changes are seen in association with reduced contractile ability of the muscles. Among others, different congenital myopathies include:
(G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle),
(G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers),
(G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers) is a rare muscle wasting disorder that occurs in three forms:
The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- (G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle),
- (G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers),
- (G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers) is a rare muscle wasting disorder that occurs in three forms:
The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
- A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
- The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- (G71.3) Mitochondrial myopathies are due to defects in mitochondria, which provide a critical source of energy for muscle.
- (G72.3) Familial periodic paralysis
- (G72.4) Inflammatory myopathies are caused by problems with the immune system attacking components of the muscle, leading to signs of inflammation in the muscle.
- (G73.6) Metabolic myopathies result from defects in biochemical metabolism that primarily affect muscle
(G73.6/E74.0) Glycogen storage diseases may affect muscle
(G73.6/E75) Lipid storage disorder
- (G73.6/E74.0) Glycogen storage diseases may affect muscle
- (G73.6/E75) Lipid storage disorder
- (M33.0-M33.1) Dermatomyositis, (M33.2) polymyositis, inclusion body myositis, and related myopathies
- (M61) Myositis ossificans
- (M62.89) Rhabdomyolysis and (R82.1) myoglobinurias
- Common muscle (R25.2) cramps and (M25.6) stiffness, and (R29.0) tetany
# Causes
## Life Threatening Causes
- Amyloidosis
- Malignancy
- Osteomalacia
- Polymyositis
- Sarcoidosis
## Common Causes
- Aconitase deficiency
- Becker muscular dystrophy
- Brody myopathy
- Caveolin-3 related distal myopathy
- Congenital muscular dystrophy
- Desmin-related myopathy
- Distal myopathy 2
- Duchenne muscular dystrophy
- Emery-dreifuss muscular dystrophy
- Familial partial lipodystrophy type 2
- Laing distal myopathy
- Lama2-related muscular dystrophy
- Limb girdle muscular dystrophy
- Mitochondrial myopathy
- Mitochondrial trifunctional protein deficiency
- Miyoshi muscular dystrophy 2
- Muscular dystrophy
- Myoneurogastrointestinal encephalopathy syndrome
- Myosin storage myopathy
- Myotonia congenita
- Myotonic dystrophy
- Nonaka myopathy
- Osteomalacia
- Polymyositis
- Rigid spine muscular dystrophy
- Rippling muscle disease
- Salih myopathy
- Spheroid body myopathy
- Tubular aggregate myopathy
- Ullrich congenital muscular dystrophy
- Welander muscular dystrophy
## Causes by Organ System
## Causes in Alphabetical Order
- Aconitase deficiency
- Addison's disease
- Adenosine monophosphate deaminase deficiency
- Alcoholism
- Aldolase a deficiency
- Alpha-mannosidase deficiency
- Amish nemaline myopathy
- Amyloidosis
- Anoctaminopathy
- Arnold stickler bourne syndrome
- Arthrogryposis
- Atorvastatin
- Barth syndrome
- Becker muscular dystrophy
- Bethlem myopathy
- Bezafibrate
- Borud syndrome
- Brody myopathy
- Brown recluse spider poisoning
- Calpainopathy
- Carey-fineman-ziter syndrome
- Carnitine deficiency
- Carnitine palmitoyltransferase 2 deficiency
- Caveolin-3 related distal myopathy
- Chanarin-dorfman disease
- Chloroquine
- Christian syndrome 1
- Chronic hypokalemia
- Clevudine
- Colchicine
- Congenital muscular dystrophy
- Cushing's disease
- Cytochrome-c oxidase deficiency
- Dermatomyositis
- Desmin-related myopathy
- Diabetes
- Distal myopathy 2
- Duchenne muscular dystrophy
- Efavirenz
- Emery-dreifuss muscular dystrophy
- Ethanol
- Familial partial lipodystrophy type 2
- Forbes disease
- Freeman-sheldon syndrome
- Fukuyama congenital muscular dystrophy
- Gigantism
- Glutaric acidemia type 2
- Glycerol kinase deficiency
- Glycogen branching deficiency
- Glycogen storage diseases
- Glycogenosis
- Hereditary fibrosing poikiloderma
- Hiv-1 disease
- Hypercalcemia
- Hyperkalemia
- Hypermagnesemia
- Hyperparathyroidism
- Hyperthyroidism
- Hypocalcaemia
- Hypokalaemia
- Hyponatremia
- Hypothyroidism
- Kearns-sayre syndrome
- Lactate dehydrogenase deficiency
- Laing distal myopathy
- Lama2-related muscular dystrophy
- Limb girdle muscular dystrophy
- Long chain hydroxyacyl-coa dehydrogenase deficiency
- Lundberg ii syndrome
- Malignancy
- Malignant hyperthermia
- Marinesco-sjogren-garland syndrome
- Melas
- Merrf
- Mitochondrial myopathy
- Mitochondrial trifunctional protein deficiency
- Miyoshi muscular dystrophy 2
- Molybdenum cofactor deficiency
- Muscle-eye-brain disease
- Muscular dystrophy
- Myoneurogastrointestinal encephalopathy syndrome
- Myosin storage myopathy
- Myotonia congenita
- Myotonic dystrophy
- Neutral lipid storage disease
- Niacin
- Nonaka myopathy
- Osteomalacia
- Periodic paralysis
- Phencyclidine
- Phosphogylcerate mutase 2 deficiency
- Plasma membrane carnitine transporter deficiency
- Polymyositis
- Polyneuropathy
- Pork tapeworm
- Pravastatin
- Prednisolone
- Progressive external ophthalmoplegia
- Proximal renal tubular acidosis
- Rickets
- Rigid spine muscular dystrophy
- Rippling muscle disease
- Rosuvastatin
- Salih myopathy
- Sarcoidosis
- Short chain acyl-coa dehydrogenase deficiency
- Simvastatin
- Spheroid body myopathy
- Steroids
- Stormorken syndrome
- Subacute necrotising encephalomyelopathy
- Tel hashomer camptodactyly syndrome
- Telbivudine
- Thyroid eye disease
- Tk2-related mitochondrial dna depletion syndrome
- Triosephosphate isomerase deficiency
- Tubular aggregate myopathy
- Type iii glycogen storage disease
- Udd-markesbery tardive muscular dystrophy
- Ullrich congenital muscular dystrophy
- Walker-warburg syndrome
- Welander muscular dystrophy
- Wieacker-wolff syndrome
- Woods black norbury syndrome
- Xanthine oxidase deficiency
- Zidovudine
# Differential Diagnosis of Muscle Weakness
To review the differential diagnosis of Proximal muscle weakness, click here.
To review the differential diagnosis of Distal muscle weakness, click here.
To review the differential diagnosis of inflammatory myopathy, click here.
To review the differential diagnosis of Muscle weakness and Fever, click here.
To review the differential diagnosis of Muscle weakness and Myalgia, click here.
To review the differential diagnosis of Muscle weakness and Gait abnormality, click here.
To review the differential diagnosis of Muscle weakness and Neuropathy, click here.
To review the differential diagnosis of Muscle weakness and stiffness, click here.
To review the differential diagnosis of Muscle weakness and Myoglobinuria, click here.
To review the differential diagnosis of Muscle weakness and Atrophy, click here.
# Treatment
Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and even acupuncture are current treatments for a variety of myopathies.
# Prognosis
The prognosis for individuals with a myopathy varies. Some individuals have a normal life span and little or no disability. For others, however, the disorder may be progressive, severely disabling, life-threatening, or fatal. | Myopathy
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In medicine, a myopathy is a neuromuscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease (myo- Greek μυσ "muscle" + pathy Greek "suffering"). This meaning implies that the primary defect is within the muscle, as opposed to the nerves ("neuropathies" or "neurogenic" disorders) or elsewhere (e.g., the brain etc.). Muscle cramps, stiffness, and spasm can also be associated with myopathy.
# Classes
Because myopathy is such a general term, there are several classes of myopathy.... (ICD-10 codes are provided where available.)
- (G71.0) Dystrophies (or muscular dystrophies) are a subgroup of myopathies characterized by muscle degeneration and regeneration. Clinically, muscular dystrophies are typically progressive, because the muscles' ability to regenerate is eventually lost, leading to progressive weakness, often leading to use of a wheelchair, and eventually death, usually related to respiratory weakness.
- (G71.1) Myotonia
Neuromyotonia
- Neuromyotonia
- (G71.2) The congenital myopathies do not show evidence for either a progressive dystrophic process (i.e., muscle death) or inflammation, but instead characteristic microscopic changes are seen in association with reduced contractile ability of the muscles. Among others, different congenital myopathies include:
(G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle),
(G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers),
(G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers) is a rare muscle wasting disorder that occurs in three forms:
The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- (G71.2) nemaline myopathy (characterized by presence of "nemaline rods" in the muscle),
- (G71.2) multi/minicore myopathy (characterized by multiple small "cores" or areas of disruption in the muscle fibers),
- (G71.2) centronuclear myopathy (or myotubular myopathy) (in which the nuclei are abnormally found in the center of the muscle fibers) is a rare muscle wasting disorder that occurs in three forms:
The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- The most severe form is present at birth, which is inherited as an X-linked genetic trait, and can cause severe respiratory muscle weakness. This is the form of centronuclear myopathy currently referred to as myotubular myopathy.
- A less severe form of centronuclear myopathy that may present itself at birth or in early childhood progresses slowly and is inherited as an autosomal recessive genetic trait.
- The least severe of the three forms of centronuclear myopathy first appears during the second and third decades of life and is slowly progressive; it is inherited as an autosomal dominant genetic trait.
- (G71.3) Mitochondrial myopathies are due to defects in mitochondria, which provide a critical source of energy for muscle.
- (G72.3) Familial periodic paralysis
- (G72.4) Inflammatory myopathies are caused by problems with the immune system attacking components of the muscle, leading to signs of inflammation in the muscle.
- (G73.6) Metabolic myopathies result from defects in biochemical metabolism that primarily affect muscle
(G73.6/E74.0) Glycogen storage diseases may affect muscle
(G73.6/E75) Lipid storage disorder
- (G73.6/E74.0) Glycogen storage diseases may affect muscle
- (G73.6/E75) Lipid storage disorder
- (M33.0-M33.1) Dermatomyositis, (M33.2) polymyositis, inclusion body myositis, and related myopathies
- (M61) Myositis ossificans
- (M62.89) Rhabdomyolysis and (R82.1) myoglobinurias
- Common muscle (R25.2) cramps and (M25.6) stiffness, and (R29.0) tetany
# Causes
## Life Threatening Causes
- Amyloidosis
- Malignancy
- Osteomalacia
- Polymyositis
- Sarcoidosis
## Common Causes
- Aconitase deficiency
- Becker muscular dystrophy
- Brody myopathy
- Caveolin-3 related distal myopathy
- Congenital muscular dystrophy
- Desmin-related myopathy
- Distal myopathy 2
- Duchenne muscular dystrophy
- Emery-dreifuss muscular dystrophy
- Familial partial lipodystrophy type 2
- Laing distal myopathy
- Lama2-related muscular dystrophy
- Limb girdle muscular dystrophy
- Mitochondrial myopathy
- Mitochondrial trifunctional protein deficiency
- Miyoshi muscular dystrophy 2
- Muscular dystrophy
- Myoneurogastrointestinal encephalopathy syndrome
- Myosin storage myopathy
- Myotonia congenita
- Myotonic dystrophy
- Nonaka myopathy
- Osteomalacia
- Polymyositis
- Rigid spine muscular dystrophy
- Rippling muscle disease
- Salih myopathy
- Spheroid body myopathy
- Tubular aggregate myopathy
- Ullrich congenital muscular dystrophy
- Welander muscular dystrophy
## Causes by Organ System
## Causes in Alphabetical Order
- Aconitase deficiency
- Addison's disease
- Adenosine monophosphate deaminase deficiency
- Alcoholism
- Aldolase a deficiency
- Alpha-mannosidase deficiency
- Amish nemaline myopathy
- Amyloidosis
- Anoctaminopathy
- Arnold stickler bourne syndrome
- Arthrogryposis
- Atorvastatin
- Barth syndrome
- Becker muscular dystrophy
- Bethlem myopathy
- Bezafibrate
- Borud syndrome
- Brody myopathy
- Brown recluse spider poisoning
- Calpainopathy
- Carey-fineman-ziter syndrome
- Carnitine deficiency
- Carnitine palmitoyltransferase 2 deficiency
- Caveolin-3 related distal myopathy
- Chanarin-dorfman disease
- Chloroquine
- Christian syndrome 1
- Chronic hypokalemia
- Clevudine
- Colchicine
- Congenital muscular dystrophy
- Cushing's disease
- Cytochrome-c oxidase deficiency
- Dermatomyositis
- Desmin-related myopathy
- Diabetes
- Distal myopathy 2
- Duchenne muscular dystrophy
- Efavirenz
- Emery-dreifuss muscular dystrophy
- Ethanol
- Familial partial lipodystrophy type 2
- Forbes disease
- Freeman-sheldon syndrome
- Fukuyama congenital muscular dystrophy
- Gigantism
- Glutaric acidemia type 2
- Glycerol kinase deficiency
- Glycogen branching deficiency
- Glycogen storage diseases
- Glycogenosis
- Hereditary fibrosing poikiloderma
- Hiv-1 disease
- Hypercalcemia
- Hyperkalemia
- Hypermagnesemia
- Hyperparathyroidism
- Hyperthyroidism
- Hypocalcaemia
- Hypokalaemia
- Hyponatremia
- Hypothyroidism
- Kearns-sayre syndrome
- Lactate dehydrogenase deficiency
- Laing distal myopathy
- Lama2-related muscular dystrophy
- Limb girdle muscular dystrophy
- Long chain hydroxyacyl-coa dehydrogenase deficiency
- Lundberg ii syndrome
- Malignancy
- Malignant hyperthermia
- Marinesco-sjogren-garland syndrome
- Melas
- Merrf
- Mitochondrial myopathy
- Mitochondrial trifunctional protein deficiency
- Miyoshi muscular dystrophy 2
- Molybdenum cofactor deficiency
- Muscle-eye-brain disease
- Muscular dystrophy
- Myoneurogastrointestinal encephalopathy syndrome
- Myosin storage myopathy
- Myotonia congenita
- Myotonic dystrophy
- Neutral lipid storage disease
- Niacin
- Nonaka myopathy
- Osteomalacia
- Periodic paralysis
- Phencyclidine
- Phosphogylcerate mutase 2 deficiency
- Plasma membrane carnitine transporter deficiency
- Polymyositis
- Polyneuropathy
- Pork tapeworm
- Pravastatin
- Prednisolone
- Progressive external ophthalmoplegia
- Proximal renal tubular acidosis
- Rickets
- Rigid spine muscular dystrophy
- Rippling muscle disease
- Rosuvastatin
- Salih myopathy
- Sarcoidosis
- Short chain acyl-coa dehydrogenase deficiency
- Simvastatin
- Spheroid body myopathy
- Steroids
- Stormorken syndrome
- Subacute necrotising encephalomyelopathy
- Tel hashomer camptodactyly syndrome
- Telbivudine
- Thyroid eye disease
- Tk2-related mitochondrial dna depletion syndrome
- Triosephosphate isomerase deficiency
- Tubular aggregate myopathy
- Type iii glycogen storage disease
- Udd-markesbery tardive muscular dystrophy
- Ullrich congenital muscular dystrophy
- Walker-warburg syndrome
- Welander muscular dystrophy
- Wieacker-wolff syndrome
- Woods black norbury syndrome
- Xanthine oxidase deficiency
- Zidovudine
# Differential Diagnosis of Muscle Weakness
To review the differential diagnosis of Proximal muscle weakness, click here.
To review the differential diagnosis of Distal muscle weakness, click here.
To review the differential diagnosis of inflammatory myopathy, click here.
To review the differential diagnosis of Muscle weakness and Fever, click here.
To review the differential diagnosis of Muscle weakness and Myalgia, click here.
To review the differential diagnosis of Muscle weakness and Gait abnormality, click here.
To review the differential diagnosis of Muscle weakness and Neuropathy, click here.
To review the differential diagnosis of Muscle weakness and stiffness, click here.
To review the differential diagnosis of Muscle weakness and Myoglobinuria, click here.
To review the differential diagnosis of Muscle weakness and Atrophy, click here.
# Treatment
Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and even acupuncture are current treatments for a variety of myopathies.
# Prognosis
The prognosis for individuals with a myopathy varies. Some individuals have a normal life span and little or no disability. For others, however, the disorder may be progressive, severely disabling, life-threatening, or fatal. | https://www.wikidoc.org/index.php/Ddx:Myopathy | |
462a969fd665ed32cae6ec9f0007cda0857f7bc7 | wikidoc | Nocturia | Nocturia
Steven C. Campbell, M.D., Ph.D.; Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S Nasrin Nikravangolsefid, MD-MPH
# Overview
Nocturia (derived from Latin nox, night, and Greek ούρα, urine), also called nycturia (Greek νυκτουρία), is the need to get up during the night in order to urinate, thus interrupting sleep. Its occurrence is more frequent in the elderly. Nocturia could result simply from too much liquid intake before going to bed, or it could be a symptom of a larger problem, such as chronic renal failure, urinary incontinence, Interstitial Cystitis, diabetes, benign prostatic hyperplasia, Ureteropelvic junction obstruction or prostate cancer.
# Historical Perspective
- Nocturia was defined by International Continence Society (ICS) in 2002, as the need to wake up one or more times at nights to void.
- Clinical definition of nocturia is awaking from sleep to urinate two or more that two times per night.
The association between and was made in/during .
In , was the first to discover the association between and the development of .
In , mutations were first implicated in the pathogenesis of .
There have been several outbreaks of , including -----.
In , was developed by to treat/diagnose .
# Pathophysiology
- It is thought that nocturia is caused by a number of factors, including
urological disorders
abnormalities of bladder capacity
prostate enlargement
urine overproduction due to
depletion of third-space fluid in overload states following a recumbent position during sleep
-verproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
medications such as diuretics
behavioral factors such as high water intake at night
- urological disorders
abnormalities of bladder capacity
prostate enlargement
- abnormalities of bladder capacity
- prostate enlargement
- urine overproduction due to
depletion of third-space fluid in overload states following a recumbent position during sleep
-verproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
medications such as diuretics
behavioral factors such as high water intake at night
- depletion of third-space fluid in overload states following a recumbent position during sleep
- overproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
- sleep apnea
- congestive heart failure
- deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
- medications such as diuretics
- behavioral factors such as high water intake at night
- AVP regulates urine production by antidiuretic effects in the collecting system in the kidneys, resulted in
increasing water reabsorption
decreasing urine volume
- increasing water reabsorption
- decreasing urine volume
- AVP deficiency or AVP dysfunction leads to decreasing urine concentration, increasing urine volume and nocturia.
# Causes
## Causes by Pathogenesis
### Causes Due to Hormonal Imbalance
### Causes Due to Vesical Problems
## Causes by Organ System
## Causes in Alphabetical Order
- Anxiety disorders
- Benign prostatic hyperplasia
- Bicalutamide
- Bladder outlet obstruction
- Cardiac glycosides
- Chronic renal failure
- Demeclocycline
- Depression
- Detrusor hyperactivity
- Diabetes
- Diabetes insipidus
- Diuretics
- Excessive vitamin D intake
- Granulomatous prostatitis
- Heart failure
- Interstitial cystitis
- Learned voiding dysfunction
- Lithium
- Liver failure
- Methoxyflurane
- Nephrotic syndrome
- Neurogenic bladder
- Obesity
- Obstructive sleep apnea
- Parkinson disease
- Phenytoin
- Primary hyperaldosteronism
- Propoxyphene
- Primary polydipsia
- Prostate cancer
- Recurrent UTI
- Restless leg syndrome
- Tiagabine
- Ureteropelvic junction obstruction
- Urge incontinence
- Venous insufficiency
# Differentiating ((Page name)) from other Diseases
must be differentiated from other diseases that cause , , and , such as , , and .
OR
must be differentiated from , , and .
# Epidemiology and Demographics
- The prevalence of nocturia ≥ 1 voids is approximately 69000 per 100,000 men aged ≥ 40 years and 76000 per 100,000 women aged ≥ 40 years in the United States, United Kingdom, and Sweden.
- The prevalence of nocturia ≥ 2 voids in population aged 20-30 years is approximately 4000 to 18000 per 100,000 women and 2000 to 17000 per 100,000 men.
- The prevalence of nocturia ≥ 2 voids in population aged 70-80 years is 28000 to 62000 per 100,000 women and 29000 to 59000 per 100,000 men.
- The prevalence of nocturia ≥ 2 voids in in Canada, Germany, Italy, Sweden, and the United Kingdom is 13000 to 17000 per 100,000 individuals aged < 40 years and 20000 to 21000 per 100,000 middle-aged populations and 35000 to 36000 per 100,000 individuals aged ≥ 60 years.
- The incidence of nocturia increases with age.
- Nocturia can affect younger people as 1 from 5 or 6 younger population wake up at least two times per night to void.
- non-Hispanic black men are more likely to develop nocturia.
- nocturia affects men and women equally. However, nocturia incidence are more in young women than young men, and also old men are more likely to develop nocturia than old women.
# Risk Factors
- Common risk factors in the development of nocturia include
aging
Hispanic and Black race
history of nocturia during childhood
history of pre-existing conditions
Diabetes mellitus
Diabetes insipidus
Hypertension
Arthritis
Airway disease such as Asthma
history of psychological disease
Depression
Anxiety disorders
history of diuretic intake
- aging
- Hispanic and Black race
- history of nocturia during childhood
- history of pre-existing conditions
Diabetes mellitus
Diabetes insipidus
Hypertension
Arthritis
Airway disease such as Asthma
- Diabetes mellitus
- Diabetes insipidus
- Hypertension
- Arthritis
- Airway disease such as Asthma
- history of psychological disease
Depression
Anxiety disorders
- Depression
- Anxiety disorders
- history of diuretic intake
- Potent risk factors in the development of nocturia in men include
prostatitis
benign prostatic hyperplasia
prostate cancer
- prostatitis
- benign prostatic hyperplasia
- prostate cancer
- Potent risk factors in the development of nocturia in women include
high BMI
Heart disease
Inflammatory bowel disease
Uterine prolapse
Hysterectomy
Menopause
recurrent UTI
- high BMI
- Heart disease
- Inflammatory bowel disease
- Uterine prolapse
- Hysterectomy
- Menopause
- recurrent UTI
# Screening
There is insufficient evidence to recommend routine screening for nocturia.
# Natural History, Complications, and Prognosis
- Common complications of nocturia include
Sleep disorders
Depression
anxiety disorders
lower quality of life
increased risk of falling and bone fracture
increased mortality
- Sleep disorders
- Depression
- anxiety disorders
- lower quality of life
- increased risk of falling and bone fracture
- increased mortality
# Diagnosis
## Diagnostic Study of Choice
- The diagnosis of nocturia is based on the clinical history defined by International Continence Society (ICS) in 2002, which includes wake up at night ≥1 times to void.
- According to new revised definition in 2017 , nocturia is to wake up to void during the sleep period.
- Bladder diary should be asked from the patients, including
the amount of water intake
the time of water intake
time and volume of urination
the number of urinations during the day
the number of nocturia (urination during the sleep),
the number of urinations and the amount of urine production during the day
- the amount of water intake
- the time of water intake
- time and volume of urination
the number of urinations during the day
the number of nocturia (urination during the sleep),
the number of urinations and the amount of urine production during the day
- the number of urinations during the day
- the number of nocturia (urination during the sleep),
- the number of urinations and the amount of urine production during the day
- Frequency- volume charts can be diagnostic for nocturia.
## History and Symptoms
- The most common symptoms of nocturia include passing urine, urgency and frequency at nights.
- History of fluid, alcohol and caffeine intake, urinary symptoms, medications , sleep disorders should be asked from the patients.
Some medications that cause nocturia include diuretics, amlodipine and nifedipine should be discontinued.
- Some medications that cause nocturia include diuretics, amlodipine and nifedipine should be discontinued.
## Physical Examination
- physical examination should include
Checking Blood pressure
digital rectal examination of the prostate in men and pelvic examination in women
checking edema of the lower limbs
checking genitalia diseases (phimosis, meatal stenosis or cancer)
abdominal examination especially bladder to assess urinary retention
calculating BMI and/or waist circumference
filling the chart of Frequency-volume for at least 3 days
- Checking Blood pressure
- digital rectal examination of the prostate in men and pelvic examination in women
- checking edema of the lower limbs
- checking genitalia diseases (phimosis, meatal stenosis or cancer)
- abdominal examination especially bladder to assess urinary retention
- calculating BMI and/or waist circumference
- filling the chart of Frequency-volume for at least 3 days
## Laboratory Findings
- Laboratory tests that should be helpful for the diagnosis of nocturia include
urine analysis with urine culture to rule out urinary tract infection
serum electrolytes
renal function tests such as BUN, creatinine, GFR
serum glucose level and HbA1c to rule out diabetes mellitus
lipid profile
PSA level to rule out prostate cancer and BPH
- urine analysis with urine culture to rule out urinary tract infection
- serum electrolytes
- renal function tests such as BUN, creatinine, GFR
- serum glucose level and HbA1c to rule out diabetes mellitus
- lipid profile
- PSA level to rule out prostate cancer and BPH
## Electrocardiogram
There are no ECG findings associated with nocturia.
## X-ray
There are no x-ray findings associated with nocturia.
## Ultrasound
- ultrasound may be helpful in the diagnosis of nocturia associated conditions. Ultrasound can measure postvoid residual volume and bladder wall thickness.
## CT scan
- There are no CT scan findings associated with nocturia. However, a CT scan may be helpful in the diagnosis of bladder, prostate and urinary tracts abnormalities.
## MRI
There are no MRI findings associated with nocturia.
## Other Imaging Findings
There are no other imaging findings associated with .
OR
may be helpful in the diagnosis of . Findings on an suggestive of/diagnostic of include , , and .
## Other Diagnostic Studies
- Cystoscopy may be helpful in the diagnosis of bladder abnormalities that cause nocturia.
# Treatment
## Medical Therapy
## Treatment
- Treatment options for nocturia depend on the underlying causes.
- Behavioral modification includes
limiting fluid intake in the evening
avoiding alcohol, coffee and tea
treating underlying conditions such as chronic constipation, diabetes mellitus, diabetes insipidus
elevation of the lower limbs in the evening
avoiding diuretics intake in the evening and night
physical exercise
- limiting fluid intake in the evening
- avoiding alcohol, coffee and tea
- treating underlying conditions such as chronic constipation, diabetes mellitus, diabetes insipidus
- elevation of the lower limbs in the evening
- avoiding diuretics intake in the evening and night
- physical exercise
- Pharmacologic medical therapies for nocturia include
desmopressin (arginine vasopressin)
It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation.
α-blockers
antimuscarinics
phosphodiesterase type 5 inhibitors
Botulinum toxin
- desmopressin (arginine vasopressin)
It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation.
- It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
- It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation.
- α-blockers
- antimuscarinics
- phosphodiesterase type 5 inhibitors
- Botulinum toxin
## Surgery
Surgical intervention is not recommended for the management of .
OR
Surgery is not the first-line treatment option for patients with . Surgery is usually reserved for patients with either , , and
OR
The mainstay of treatment for is medical therapy. Surgery is usually reserved for patients with either , , and/or .
OR
The feasibility of surgery depends on the stage of at diagnosis.
OR
Surgery is the mainstay of treatment for .
## Primary Prevention
- Effective measures for the primary prevention of nocturia include lifestyle modifications such as
reducing intake of fluid, caffeine, alcohol, diuretics in the evening and night
less salt intake
take naps in the afternoon
weight loss in obese and overweight individuals
urination before going to bed
using compression stocks or elevating legs to reduce edema
- reducing intake of fluid, caffeine, alcohol, diuretics in the evening and night
- less salt intake
- take naps in the afternoon
- weight loss in obese and overweight individuals
- urination before going to bed
- using compression stocks or elevating legs to reduce edema
## Secondary Prevention
There are no established measures for the secondary prevention of nocturia. | Nocturia
For patient information click here
Template:Search infobox
Steven C. Campbell, M.D., Ph.D.; Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [1] Nasrin Nikravangolsefid, MD-MPH [2]
# Overview
Nocturia (derived from Latin nox, night, and Greek [τα] ούρα, urine), also called nycturia (Greek νυκτουρία), is the need to get up during the night in order to urinate, thus interrupting sleep. Its occurrence is more frequent in the elderly. Nocturia could result simply from too much liquid intake before going to bed, or it could be a symptom of a larger problem, such as chronic renal failure, urinary incontinence, Interstitial Cystitis, diabetes, benign prostatic hyperplasia, Ureteropelvic junction obstruction[1] or prostate cancer.
# Historical Perspective
- Nocturia was defined by International Continence Society (ICS) in 2002, as the need to wake up one or more times at nights to void. [2]
- Clinical definition of nocturia is awaking from sleep to urinate two or more that two times per night. [3] [4]
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
# Pathophysiology
- It is thought that nocturia is caused by a number of factors, including[5][6] [7]
urological disorders
abnormalities of bladder capacity
prostate enlargement
urine overproduction due to
depletion of third-space fluid in overload states following a recumbent position during sleep
overproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
medications such as diuretics
behavioral factors such as high water intake at night
- urological disorders
abnormalities of bladder capacity
prostate enlargement
- abnormalities of bladder capacity
- prostate enlargement
- urine overproduction due to
depletion of third-space fluid in overload states following a recumbent position during sleep
overproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
medications such as diuretics
behavioral factors such as high water intake at night
- depletion of third-space fluid in overload states following a recumbent position during sleep
- overproduction of atrial natriuretic peptide (ANP) caused by
sleep apnea
congestive heart failure
- sleep apnea
- congestive heart failure
- deficiency or dysfunction of antidiuretic hormone (ADH) or arginine vasopressin (AVP)
- medications such as diuretics
- behavioral factors such as high water intake at night
- AVP regulates urine production by antidiuretic effects in the collecting system in the kidneys, resulted in[6]
increasing water reabsorption
decreasing urine volume
- increasing water reabsorption
- decreasing urine volume
- AVP deficiency or AVP dysfunction leads to decreasing urine concentration, increasing urine volume and nocturia. [6][7]
# Causes
## Causes by Pathogenesis
### Causes Due to Hormonal Imbalance
### Causes Due to Vesical Problems
## Causes by Organ System
## Causes in Alphabetical Order
- Anxiety disorders
- Benign prostatic hyperplasia
- Bicalutamide
- Bladder outlet obstruction
- Cardiac glycosides
- Chronic renal failure
- Demeclocycline
- Depression
- Detrusor hyperactivity
- Diabetes
- Diabetes insipidus
- Diuretics
- Excessive vitamin D intake
- Granulomatous prostatitis
- Heart failure
- Interstitial cystitis
- Learned voiding dysfunction
- Lithium
- Liver failure
- Methoxyflurane
- Nephrotic syndrome
- Neurogenic bladder
- Obesity
- Obstructive sleep apnea
- Parkinson disease
- Phenytoin
- Primary hyperaldosteronism
- Propoxyphene
- Primary polydipsia
- Prostate cancer
- Recurrent UTI
- Restless leg syndrome
- Tiagabine
- Ureteropelvic junction obstruction
- Urge incontinence
- Venous insufficiency
# Differentiating ((Page name)) from other Diseases
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
# Epidemiology and Demographics
- The prevalence of nocturia ≥ 1 voids is approximately 69000 per 100,000 men aged ≥ 40 years and 76000 per 100,000 women aged ≥ 40 years in the United States, United Kingdom, and Sweden. [8] [6]
- The prevalence of nocturia ≥ 2 voids in population aged 20-30 years is approximately 4000 to 18000 per 100,000 women and 2000 to 17000 per 100,000 men. [9]
- The prevalence of nocturia ≥ 2 voids in population aged 70-80 years is 28000 to 62000 per 100,000 women and 29000 to 59000 per 100,000 men. [9]
- The prevalence of nocturia ≥ 2 voids in in Canada, Germany, Italy, Sweden, and the United Kingdom is 13000 to 17000 per 100,000 individuals aged < 40 years and 20000 to 21000 per 100,000 middle-aged populations and 35000 to 36000 per 100,000 individuals aged ≥ 60 years. [10]
- The incidence of nocturia increases with age. [9]
- Nocturia can affect younger people as 1 from 5 or 6 younger population wake up at least two times per night to void. [9] [10]
- non-Hispanic black men are more likely to develop nocturia. [11] [6]
- nocturia affects men and women equally. However, nocturia incidence are more in young women than young men, and also old men are more likely to develop nocturia than old women. [12]
# Risk Factors
- Common risk factors in the development of nocturia include[13] [14][15]
aging
Hispanic and Black race
history of nocturia during childhood
history of pre-existing conditions
Diabetes mellitus
Diabetes insipidus
Hypertension
Arthritis
Airway disease such as Asthma
history of psychological disease
Depression
Anxiety disorders
history of diuretic intake
- aging
- Hispanic and Black race
- history of nocturia during childhood
- history of pre-existing conditions
Diabetes mellitus
Diabetes insipidus
Hypertension
Arthritis
Airway disease such as Asthma
- Diabetes mellitus
- Diabetes insipidus
- Hypertension
- Arthritis
- Airway disease such as Asthma
- history of psychological disease
Depression
Anxiety disorders
- Depression
- Anxiety disorders
- history of diuretic intake
- Potent risk factors in the development of nocturia in men include[13][15]
prostatitis
benign prostatic hyperplasia
prostate cancer
- prostatitis
- benign prostatic hyperplasia
- prostate cancer
- Potent risk factors in the development of nocturia in women include[13]
high BMI
Heart disease
Inflammatory bowel disease
Uterine prolapse
Hysterectomy
Menopause
recurrent UTI
- high BMI
- Heart disease
- Inflammatory bowel disease
- Uterine prolapse
- Hysterectomy
- Menopause
- recurrent UTI
# Screening
There is insufficient evidence to recommend routine screening for nocturia.
# Natural History, Complications, and Prognosis
- Common complications of nocturia include[9][8][16][17][18][6][19]
Sleep disorders
Depression
anxiety disorders
lower quality of life
increased risk of falling and bone fracture
increased mortality
- Sleep disorders
- Depression
- anxiety disorders
- lower quality of life
- increased risk of falling and bone fracture
- increased mortality
# Diagnosis
## Diagnostic Study of Choice
- The diagnosis of nocturia is based on the clinical history defined by International Continence Society (ICS) in 2002, which includes wake up at night ≥1 times to void. [20]
- According to new revised definition in 2017 , nocturia is to wake up to void during the sleep period. [21]
- Bladder diary should be asked from the patients, including [22]
the amount of water intake
the time of water intake
time and volume of urination
the number of urinations during the day
the number of nocturia (urination during the sleep),
the number of urinations and the amount of urine production during the day
- the amount of water intake
- the time of water intake
- time and volume of urination
the number of urinations during the day
the number of nocturia (urination during the sleep),
the number of urinations and the amount of urine production during the day
- the number of urinations during the day
- the number of nocturia (urination during the sleep),
- the number of urinations and the amount of urine production during the day
- Frequency- volume charts can be diagnostic for nocturia. [4]
## History and Symptoms
- The most common symptoms of nocturia include passing urine, urgency and frequency at nights. [4]
- History of fluid, alcohol and caffeine intake, urinary symptoms, medications , sleep disorders should be asked from the patients. [4]
Some medications that cause nocturia include diuretics, amlodipine and nifedipine should be discontinued.
- Some medications that cause nocturia include diuretics, amlodipine and nifedipine should be discontinued.
## Physical Examination
- physical examination should include [4]
Checking Blood pressure
digital rectal examination of the prostate in men and pelvic examination in women
checking edema of the lower limbs
checking genitalia diseases (phimosis, meatal stenosis or cancer)
abdominal examination especially bladder to assess urinary retention
calculating BMI and/or waist circumference
filling the chart of Frequency-volume for at least 3 days
- Checking Blood pressure
- digital rectal examination of the prostate in men and pelvic examination in women
- checking edema of the lower limbs
- checking genitalia diseases (phimosis, meatal stenosis or cancer)
- abdominal examination especially bladder to assess urinary retention
- calculating BMI and/or waist circumference
- filling the chart of Frequency-volume for at least 3 days
## Laboratory Findings
- Laboratory tests that should be helpful for the diagnosis of nocturia include [4]
urine analysis with urine culture to rule out urinary tract infection
serum electrolytes
renal function tests such as BUN, creatinine, GFR
serum glucose level and HbA1c to rule out diabetes mellitus
lipid profile
PSA level to rule out prostate cancer and BPH
- urine analysis with urine culture to rule out urinary tract infection
- serum electrolytes
- renal function tests such as BUN, creatinine, GFR
- serum glucose level and HbA1c to rule out diabetes mellitus
- lipid profile
- PSA level to rule out prostate cancer and BPH
## Electrocardiogram
There are no ECG findings associated with nocturia.
## X-ray
There are no x-ray findings associated with nocturia.
## Ultrasound
- ultrasound may be helpful in the diagnosis of nocturia associated conditions. Ultrasound can measure postvoid residual volume and bladder wall thickness. [23][24]
## CT scan
- There are no CT scan findings associated with nocturia. However, a CT scan may be helpful in the diagnosis of bladder, prostate and urinary tracts abnormalities.[23]
## MRI
There are no MRI findings associated with nocturia.
## Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
## Other Diagnostic Studies
- Cystoscopy may be helpful in the diagnosis of bladder abnormalities that cause nocturia. [23]
# Treatment
## Medical Therapy
## Treatment
- Treatment options for nocturia depend on the underlying causes.
- Behavioral modification includes [22] [4]
limiting fluid intake in the evening
avoiding alcohol, coffee and tea
treating underlying conditions such as chronic constipation, diabetes mellitus, diabetes insipidus
elevation of the lower limbs in the evening
avoiding diuretics intake in the evening and night
physical exercise
- limiting fluid intake in the evening
- avoiding alcohol, coffee and tea
- treating underlying conditions such as chronic constipation, diabetes mellitus, diabetes insipidus
- elevation of the lower limbs in the evening
- avoiding diuretics intake in the evening and night
- physical exercise
- Pharmacologic medical therapies for nocturia include
desmopressin (arginine vasopressin) [22]
It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation. [25]
α-blockers
antimuscarinics
phosphodiesterase type 5 inhibitors
Botulinum toxin
- desmopressin (arginine vasopressin) [22]
It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation. [25]
- It decreases urine volume through vasopressin V2 receptors, which leads to increase water reabsorption in renal tubules.
- It is the preferred drug for the treatment of nocturia due to nocturnal polyuria according to the European Association of Urology (EAU) recommendation. [25]
- α-blockers
- antimuscarinics
- phosphodiesterase type 5 inhibitors
- Botulinum toxin
## Surgery
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
## Primary Prevention
- Effective measures for the primary prevention of nocturia include lifestyle modifications such as [4][23]
reducing intake of fluid, caffeine, alcohol, diuretics in the evening and night
less salt intake
take naps in the afternoon
weight loss in obese and overweight individuals
urination before going to bed
using compression stocks or elevating legs to reduce edema
- reducing intake of fluid, caffeine, alcohol, diuretics in the evening and night
- less salt intake
- take naps in the afternoon
- weight loss in obese and overweight individuals
- urination before going to bed
- using compression stocks or elevating legs to reduce edema
## Secondary Prevention
There are no established measures for the secondary prevention of nocturia. | https://www.wikidoc.org/index.php/Ddx:Nocturia | |
ae1ef8d17a217fd1eacda5ca73a5bd611b1cdf05 | wikidoc | Priapism | Priapism
For patient information page click here
Steven C. Campbell, M.D., Ph.D.
Please Join in Editing This Page and Apply to be an Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Priapism is a potentially harmful medical condition in which the erect penis does not return to its flaccid state (despite the absence of both physical and psychological stimulation) within about four hours. It is often painful. Priapism is considered a medical emergency, which should receive proper treatment by a qualified medical practitioner.
The name comes from the Greek god Priapus, referring to the myth that he was ironically punished by the other gods for attempting to rape a goddess, by being given a huge (but useless) set of wooden genitals.
# Causes
The causative mechanisms are poorly understood but involve complex neurological and vascular factors.
Priapism may be associated with haematological disorders, especially sickle-cell disease, and other conditions such as leukemia, thalassemia, and Fabry's disease, and neurologic disorders such as spinal cord lesions and spinal cord trauma (priapism has been reported in hanging victims; see death erection).
Priapism can be caused by medications. The most common medications that cause priapism are intra-cavernous injections for treatment of erectile dysfunction (papaverine, alprostadil). Other groups reported are antihypertensives, antipsychotics (e.g chlorpromazine, clozapine), antidepressants (most notably trazodone), anticoagulants, cantharides (Spanish Fly) and recreational drugs (alcohol and cocaine). Phosphodiesterase type-5 (PDE5) inhibitors such as sildenafil (popularly Viagra), tadalafil and vardenafil have very rarely been implicated, and probably do not cause priapism. PDE-5 inhibitors have even been evaluated as preventive treatment for recurrent priapism.
Female Priapism is a very rare disorder.
- Alfuzosin
- Alprostadil
- Chlorpromazine
- Iloperidone
- Indinavir
- Lorcaserin
- Methylphenidate
- Nandrolone
- Oxandrolone
- Oxymetholone
- Oxcarbazepine
- Pramipexole
- Sertraline
- Tamsulosin
- Risperidone
# Complications
Potential complications include ischemia, clotting of the blood retained in the penis (thrombosis), and damage to the blood vessels of the penis which may result in an impaired erectile function or impotence. In serious cases, the ischemia may result in gangrene, which could necessitate penis removal.
# Treatment
Medical advice should be sought immediately for cases of erection beyond four hours. Generally, this is done at an emergency department. The therapy at this stage is to aspirate blood from the corpus cavernosum under local anaesthetic. If this is still insufficient, then intra-cavernosal injections of phenylephrine are administered. This should only be performed by a trained urologist, with the patient under constant hemodynamic monitoring, as phenylephrine can cause severe hypertension, bradycardia, tachycardia, and arrhythmia.
If aspiration fails and tumescence re-occurs, surgical shunts are next attempted. These attempt to reverse the priapic state by shunting blood from the rigid corpora cavernosa into the corpus spongiosum (which contains the glans and the urethra). Distal shunts are the first step, followed by more proximal shunts.
Distal shunts, such as the Winter's, involves puncturing the glans (the distal part of the penis) into one of the cavernosa, where the old, stagnant blood is held. This causes the blood to leave the penis and return to the circulation. This procedure can be performed by a urologist at the bedside.
Proximal shunts, such as the Quackel's, are more involved and entail operative dissection in the perineum to where the corpora meet the spongiosum, making an incision in both, and suturing both openings together.
# Female Priapism
Female Priapism is very rare and normally goes undiagnosed or misdiagnosed. Emergency medical attention should be sought immediately. Treatment normally consists of medicinal pain management and hospital observation.
# Powerpoint Presentations
File:Priapism.ppt
# Footnotes
- ↑ Burnett AL, Bivalacqua TJ, Champion HC, Musicki B (2006). "Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism". Urology. 67 (5): 1043–8. doi:10.1016/j.urology.2005.11.045. PMID 16698365.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Burnett AL, Bivalacqua TJ, Champion HC, Musicki B (2006). "Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism". The journal of sexual medicine. 3 (6): 1077–84. doi:10.1111/j.1743-6109.2006.00333.x. PMID 17100941.CS1 maint: Multiple names: authors list (link)
- ↑ Montague DK, Jarow J, Broderick GA; et al. (2003). "American Urological Association guideline on the management of priapism". J. Urol. 170 (4 Pt 1): 1318–24. doi:10.1097/01.ju.0000087608.07371.ca. PMID 14501756.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) | Priapism
For patient information page click here
Template:Search infobox
Steven C. Campbell, M.D., Ph.D.
Please Join in Editing This Page and Apply to be an Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Priapism is a potentially harmful medical condition in which the erect penis does not return to its flaccid state (despite the absence of both physical and psychological stimulation) within about four hours. It is often painful. Priapism is considered a medical emergency, which should receive proper treatment by a qualified medical practitioner.
The name comes from the Greek god Priapus, referring to the myth that he was ironically punished by the other gods for attempting to rape a goddess, by being given a huge (but useless) set of wooden genitals.
# Causes
The causative mechanisms are poorly understood but involve complex neurological and vascular factors.
Priapism may be associated with haematological disorders, especially sickle-cell disease, and other conditions such as leukemia, thalassemia, and Fabry's disease, and neurologic disorders such as spinal cord lesions and spinal cord trauma (priapism has been reported in hanging victims; see death erection).
Priapism can be caused by medications. The most common medications that cause priapism are intra-cavernous injections for treatment of erectile dysfunction (papaverine, alprostadil). Other groups reported are antihypertensives, antipsychotics (e.g chlorpromazine, clozapine), antidepressants (most notably trazodone), anticoagulants, cantharides (Spanish Fly) and recreational drugs (alcohol and cocaine). Phosphodiesterase type-5 (PDE5) inhibitors such as sildenafil (popularly Viagra), tadalafil and vardenafil have very rarely been implicated, and probably do not cause priapism. PDE-5 inhibitors have even been evaluated as preventive treatment for recurrent priapism.[1][2]
Female Priapism is a very rare disorder.
- Alfuzosin
- Alprostadil
- Chlorpromazine
- Iloperidone
- Indinavir
- Lorcaserin
- Methylphenidate
- Nandrolone
- Oxandrolone
- Oxymetholone
- Oxcarbazepine
- Pramipexole
- Sertraline
- Tamsulosin
- Risperidone
# Complications
Potential complications include ischemia, clotting of the blood retained in the penis (thrombosis), and damage to the blood vessels of the penis which may result in an impaired erectile function or impotence. In serious cases, the ischemia may result in gangrene, which could necessitate penis removal.
# Treatment
Medical advice should be sought immediately for cases of erection beyond four hours. Generally, this is done at an emergency department. The therapy at this stage is to aspirate blood from the corpus cavernosum under local anaesthetic. If this is still insufficient, then intra-cavernosal injections of phenylephrine are administered. This should only be performed by a trained urologist, with the patient under constant hemodynamic monitoring, as phenylephrine can cause severe hypertension, bradycardia, tachycardia, and arrhythmia.
If aspiration fails and tumescence re-occurs, surgical shunts are next attempted. These attempt to reverse the priapic state by shunting blood from the rigid corpora cavernosa into the corpus spongiosum (which contains the glans and the urethra). Distal shunts are the first step, followed by more proximal shunts.
Distal shunts, such as the Winter's, involves puncturing the glans (the distal part of the penis) into one of the cavernosa, where the old, stagnant blood is held. This causes the blood to leave the penis and return to the circulation. This procedure can be performed by a urologist at the bedside.
Proximal shunts, such as the Quackel's, are more involved and entail operative dissection in the perineum to where the corpora meet the spongiosum, making an incision in both, and suturing both openings together.[3]
# Female Priapism
Female Priapism is very rare and normally goes undiagnosed or misdiagnosed. Emergency medical attention should be sought immediately. Treatment normally consists of medicinal pain management and hospital observation.
# Powerpoint Presentations
File:Priapism.ppt
# Footnotes
- ↑ Burnett AL, Bivalacqua TJ, Champion HC, Musicki B (2006). "Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism". Urology. 67 (5): 1043–8. doi:10.1016/j.urology.2005.11.045. PMID 16698365.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Burnett AL, Bivalacqua TJ, Champion HC, Musicki B (2006). "Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism". The journal of sexual medicine. 3 (6): 1077–84. doi:10.1111/j.1743-6109.2006.00333.x. PMID 17100941.CS1 maint: Multiple names: authors list (link)
- ↑ Montague DK, Jarow J, Broderick GA; et al. (2003). "American Urological Association guideline on the management of priapism". J. Urol. 170 (4 Pt 1): 1318–24. doi:10.1097/01.ju.0000087608.07371.ca. PMID 14501756.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) | https://www.wikidoc.org/index.php/Ddx:Priapism | |
b9b41348ef291ee23beb884a6d9c3c81e80a58ef | wikidoc | Pruritis | Pruritis
# Overview
Itch (Latin: pruritus) is defined as an unpleasant sensation that evokes the desire or reflex to scratch. Itch has many similarities to pain and both are unpleasant sensory experiences but their behavioral response patterns are different. Pain creates a reflex withdrawal while itch leads to a scratch reflex. Unmyelinated nerve fibers for itch and pain both originate in the skin, however information for them are conveyed centrally in two distinct systems that both use the same peripheral nerve bundle and spinothalamic tract.
Historically, the sensations of itch and pain have not been considered to be independent of each other until recently where it was found that itch has several features in common with pain but exhibits notable differences. The physiological mechanisms of itch are currently poorly understood and this is mainly due to the lack of animal models of itch. Pruritic stimuli mostly create the same reactions as noxious stimuli in experimental animals, but humans are capable of discerning the distinct features of itch and pain. Therefore human studies have provided most of the information regarding the processing of pruritic stimuli.
# Mechanism
Itch can originate in the peripheral nervous system (dermal or neuropathic) or in the central nervous system (neuropathic, neurogenic, or psychogenic).
## Dermal/Pruritoceptive
Itch originating in the skin is considered pruritoceptive and can be induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation. The primary afferent neurons responsible for histamine induced itch are unmyelinated C-fibers. In human C-fiber nociceptors, two major classes exist: mechano-responsive nociceptors and mechano-insensitive nociceptors. Mechano-responsive nociceptors have been in shown in studies to respond to mostly pain and mechano-insensitive receptors respond mostly to itch induced by histamine. However it does not explain mechanically induced itch or when itch is produced without a flare reaction which involves no histamine. Therefore it is possible that pruritoceptive nerve fibers have different classes of fibers, which is currently unclear in current research.
Studies have been done to show that itch receptors are only found on the top two skin layers, the epidermis and the epidermal/dermal transition layers. Shelley and Arthur had verified the depth by injecting individual itch powder spicules (Mucuna pruriens) and found that maximal sensitivity was found at the basal cell layer or the innermost layer of the epidermis. Surgical removal of those skin layers removed the ability for a patient to perceive itch. Itch is never felt in muscle, joints, or inner organs, which show that deep tissue does not contain itch signaling apparatuses.
Sensitivity to puritic stimuli is not even across the skin and has a random spot distribution with similar density to that of pain. The same substances that elicit itch upon intracutaneous injection (injection within the skin) elicit only pain when injected subcutaneously (beneath the skin). Itch is readily abolished in skin areas treated with nociceptor excitotoxin capsaicin but remains unchanged in skin areas which were rendered touch-insensitive by pretreatment with saponins, an anti-inflammatory agent. Although experimentally induced itch can still be perceived under a complete A-fiber conduction block, it is significantly diminished. Overall, itch sensation is mediated by A-delta and C nociceptors located in the uppermost layer of the skin.
## Neuropathic
Neuropathic itch can originate at any point along the afferent pathway as a result of damage of the nervous system. They could include diseases or disorders in the central nervous system or peripheral nervous system. Examples of neuropathic itch in origin are nostalgia paresthetica, brachioradial pruritus, brain tumors, multiple sclerosis, peripheral neuropathy, and nerve irritation.
## Neurogenic
Neurogenic itch, which is itch induced centrally but with no neural damage, is often associated with increased accumulation of endogenous opioids and possibly synethetic opioids.
## Psychogenic
Itch is also associated with some psychiatric disorders such as delusions of parasitosis or related obsessive-compulsive disorders, for example neurotic scratching.
# Interactions between Itch and Pain
## Pain Inhibits Itch
The sensation of itch can be reduced by many painful sensations. Many studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat, physical rubbing/scratching, noxious chemicals, and electric shock. Any stimuli that causes pain will inhibit itching.
The inhibition of itch by painful stimuli, including heat, physical stimulus, and chemical stimulus, has been shown experimentally. In an article written by Louise Ward and others, they studied the effects of noxious and non-noxious counterstimuli, such as heat, physical vibration, or chemical stimulation on skin, in healthy adults after they had experimentally induced itch (transdermal iontophoresis of histamine) and pain (with topical mustard oil) in their skin. They found that when they induced non-noxious counterstimuli, the reduction of pain and itch was reduced only for up to 20 seconds. However when they induced noxious counterstimuli, there was a significant inhibition of itch for an extended period of time but no inhibition of pain. In addition, it was found that brief noxious stimuli created an anti-itch state for more than 30 minutes. These findings show that itch is not a subliminal form of pain and that noxious counterstimulus is likely to act through a central instead of a peripheral mechanism.
Painful electrical stimulation reduced histamine-induced itch for several hours at a distance up to 10 cm from the stimulated site, which suggests a central mode of action. A new method had been recently found, by Hans-Jorgen Nilsson and others, that is able to relieve itch without damaging the skin called cutaneous field stimulation (CFS). CFS consists of a flexible rubber plate with 16 needle-like electrodes placed regularly at 2-centimeter intervals in a 4 by 4 matrix used to electrically stimulate nerve fibers in the surface of the skin. The electrodes were stimulated continuously at 4 Hertz per electrode, pulse duration of 1 millisecond, intensity 0.4-0.8 milliamperes, and for 25 minutes. CFS resulted in a pricking and burning sensation that usually faded away very quickly. The burning sensation was still present during a selective block of impulse conduction of A-fibers in myelinated fibers indicating that nociceptive C-fibers are activated by CFS. In addition, a flare reaction had been noted to develop around the CFS electrodes which indicate activation of axon reflexes in nociceptive C-fibers. Itch, which was induced by transdermal iontophoresis of histamine, was inhibited within the skin area treated with CFS, and it was reduced 10 cm distally to a significant amount. CFS proves to offer a new method of combating itch by using painful electrical stimulation as it creates a long lasting inhibitory effect, does not create any significant skin injuries, and is simple to manage. It is able to activate powerful itch inhibitory mechanisms possibly routed through central mechanisms, which could normally be activated by scratching of the skin.
A study done by Gil Yosipovitch, Katharine Fast, and Jeffrey Bernhard showed that noxious heat and scratching was able to inhibit or decrease itch induced by transdermal iontophoresis of histamine and most interestingly, decrease skin blood flow. Twenty-one healthy volunteers participated in their study. Baseline measurements of skin blood flow were obtained on the flexor part of the forearm and then compared with skin blood flow after various stimuli. Then transdermal iontophoresis of histamine was performed and tested with various stimuli. It is well known that skin blood flow is significantly increased during mechanical scratching, warming, and noxious heat. However it is quite interesting that this study is the first to examine the changes of blood flow by stimuli during iontophoresis of histamine and how itch is perceived in those conditions. Its examination provided an unexpected result that noxious heat and scratching has an inhibitory effect.
A negative correlation was found between pain sensitivity and itch sensitivity. In a study done by Amanda Green and others, they aimed to determine itch-related genetic factors, and establish a more useful animal model for itch. They looked at 11 different inbred mouse strains and compared their scratching behavior in response to two itch inducing agents, histamine and chloroquine. Every strain revealed an inverted-U shape dose response relationship from chloroquine, indicating that moderate dosages produced more scratching than at higher dosages. An explanation is that higher dosage produces more pain and the presence of pain inhibits pain thereby lowering the amount of overall scratching. Another notable result was that histamine induced scratching occurred in female mice on average 23% more than males. Finally, it was found that mice having strains sensitive to pain were resistant to itch and vice versa.
## Peripheral Sensitization
Inflammatory mediators such as bradykinin, serotonin (5-HT) and prostaglandins, released during a painful or pruritic inflammatory condition not only activates pruriceptors but also causes acute sensitization of the nociceptors. In addition, expression of neuro growth factors (NGF) can cause structural changes in of nociceptors such as sprouting. NGF is high in injured or inflamed tissue. Increased NGF is also found in atopic dermatitis, a hereditary and non-contagious skin disease with chronic inflammation. NGF is known to up-regulate neuropeptides, especially substance P. Substance P has been found to have an important role in inducing pain however there is no confirmation that substance P directly causes acute sensitization. Instead substance P may contribute to itch by increasing neuronal sensitization and may the affect release of mast cells, which contain many granules rich in histamine, during long-term interaction.
## Central Sensitization
Noxious input to the spinal cord is known to produce central sensitization, which consists of allodynia, exaggeration of pain, and punctuate hyperalgesia, extreme sensitivity to pain. Two types of mechanical hyperalgesia can occur: 1) touch that is normally painless in the uninjured surroundings of a cut or tear can trigger painful sensations (touch-evoked hyperalgesia), and 2) a slightly painful pin prick stimulation is perceived as more painful around a focused area of inflammation (punctuate hyperalgesia). Touch-evoked hyperalgesia requires continuous firing of primary afferent nociceptors, and punctuate hyperalgesia does not require continuous firing which means it can persist for hours after a trauma and can be stronger than normally experienced. In addition, it was found that patients with neuropathic pain, histamine ionophoresis resulted in a sensation of burning pain rather than itch, which would be induced in normal healthy patients. This shows that there is spinal hypersensitivity to C-fiber input in chronic pain.
# Causes
## Common Causes
- Xerosis
- Eczema
- Psoriasis
- Sunburn
- Athlete's foot
- Insect bites
- Urushiol
- Hodgkin's disease
- Jaundice
- Polycythemia
- Scabies
- Lice
- Thyroid illness
- Shaving
- Diabetes Mellitus
- Dandruff
- Iron deficiency anemia
- Parasitic infections
- Allergies
- Morphine
- Terbinafine
- Niacin
- Simvastatin
- Cholestasis
## Causes by Organ System
## Causes in Alphabetical Order
- Acamprosate
- Acanthocheilonemiasis
- Acipimox
- Acrodermatitis chronica atrophicans
- Acrokeratosis paraneoplastica of bazex
- Acropustulosis of infancy
- Actinic granuloma
- Adrenergic conditions
- Aging
- Aids
- Alfentanil
- Allergic conjunctivitis
- Allergies
- Allopurinol
- Altretamine
- Amphetamine
- Amyloidosis
- Ancylostoma duodenale
- Angioedema
- Ascariasis
- Athlete's foot
- Atopic dermatitis
- Bacterial conjunctivitis
- Bile acid synthesis defects
- Blood transfusion and complications
- Brachioradial pruritus
- Brain abscess
- Bullous pemphigoid
- Burn wounds
- Candida albicans
- Carbimazole
- Carcinoid syndrome
- Cerebrovascular accidents
- Chilblains
- Chloroquine
- Cholestasis
- Cholestatic jaundice
- Cholinergic conditions
- Chronic eosinophilic leukemia
- Chronic fatigue syndrome
- Chronic hepatitis
- Chronic lymphocytic leukemia
- Chronic myringitis
- Cilostazol
- Cimex lectularius
- Ciprofloxacin
- Cocaine use
- Conjunctivitis
- Connective tissue diseases
- Contact dermatitis
- Creutzfeldt-jakob disease
- Cutaneous larva migrans
- Cutaneous t-cell lymphoma
- Dandruff
- Decompression sickness
- Delusional parasitosis
- Dermatitis artefacta
- Dermatitis herpetiformis
- Dermatomyositis
- Dermatophytosis
- Diabetes mellitus
- Diamino diphenylmethane
- Diffuse systemic sclerosi
- Dracunculiasis
- Drug side effect
- Drug-induced liver disease
- Dumping syndrome
- Eczema
- Elastosis perforans serpiginosa
- Eosinophilia-myalgia syndrome
- Erythema annulare centrifugum
- Erythroderma
- Erythropoietic protoporphyria
- Essential thrombocythemia
- Fabry disease
- Familial cold urticaria
- Fibromyalgia
- Fixed drug eruption
- Fox-fordyce disease
- Functional disorders
- Gestational pemphigoid
- Gnathostomiasis
- Gold salts
- Hemochromatosis
- Hepatitic c
- Hepatobiliary disease
- Hepatoma
- Herpes gestationis
- Herpes simplex
- Herpes virus 2
- Herpes zoster
- Hidradenitis suppurativa
- Hiv
- Hodgkin's disease
- Hodgkin's lymphoma
- Hookworms
- Hymenolepiasis
- Hypereosinophilic syndrome
- Hyperimmunoglobulin e (ige) syndrome
- Hyperparathyroidism
- Hyperthyroidism
- Hypoparathyroidism
- Hypothyroidism
- Id reaction
- Imipenem
- Inflammatory linear verrucous epidermal nevus
- Insect bites
- Interleukin 2
- Intrahepatic cholestasis of pregnancy
- Iron deficiency
- Jaundice
- Kerion
- Ketoconazole
- Kraurosis vulvae
- Lamellar ichthyosis
- Latex allergies
- Leptospirosis
- Leukemia
- Leukemia cutis
- Lice
- Lichen aureus
- Lichen planus
- Lichen sclerosus et atrophicus
- Lichen simplex chronicus
- Lichen striatus
- Liver cancer
- Liver failure
- Louse-borne diseases
- Lymphatic filariasis
- Macrophage activation syndrome
- Malassezia furfur
- Malignancy
- Mansonelliasis
- Mastocytosis
- Medication side effects
- Mefloquine
- Melanoma
- Mercury
- Meropenem
- Metastatic liver cancer
- Methimazole
- Methionine
- Miliaria rubra
- Mite conditions
- Morphine
- Morphoea
- Multiple endocrine neoplasia
- Multiple sclerosis
- Myelodysplastic syndrome
- Necator americanus
- Necitumumab
- Nephrogenic fibrosing dermopathy
- Neurofibromatosis
- Niacin
- Niclosamide
- Nicotinic acid
- Non-hodgkin's lymphoma
- Norfloxacin
- Notalgia paraesthetica
- Nummular dermatitis
- Obeticholic acid
- Occupational cancer
- Onchocerciasis
- Opioid use
- Palifermin
- Pancreatic islet cell cancer
- Papilloma
- Paraneoplastic syndrome
- Parasitophobia
- Parvoviral infection
- Peanut allergies
- Pediculosis
- Pediculus humanus capitis
- Pediculus humanus corporis
- Pellagra
- Pemphigoid gestationis
- Pemphigus foliaceus
- Penicillin allergy
- Permethrin
- Pfic
- Phaeohyphomycosis
- Photodermatitis
- Phthiriasis
- Pinworms
- Pityriasis alba
- Pityriasis rosea
- Pollen allergy
- Polycythemia rubra vera
- Polycythemiaistamine
- Polymorphic eruption of pregnancy
- Polymorphic light eruption
- Pompholyx
- Portal hypertension
- Postherpetic neuralgia
- Pregnancy
- Primary cutaneous amyloidosis
- Primary sclerosing cholangitis
- Propylthiouracil
- Prurigo nodularis
- Psoriasis
- Psychogenic excoriation
- Pulex irritans
- Rabies
- Remifentanil
- Renal disease
- Renal failure
- Rhabditida infections
- Rhesus isoimmunisation
- Sarcoidosis
- Sarcoptes scabiei
- Scabies
- Scars
- Schamberg's disease
- Scleroderma
- Secernentea infections
- Shaving
- Shingles
- Siltuximab
- Simeprevir
- Simvastatin
- Sjögren syndrome
- Skin allergies
- Skin conditions
- Skin rash
- Sleeping sickness
- Small-fiber neuropathies
- Starvation
- Strongyloidiasis
- Sufentanil
- Sunburn
- Swimmer's itch
- Symptomatic dermatographism
- Systemic lupus erythematosus
- Taeniasis
- Terbinafine
- Threadworm
- Thyroid disease
- Tinea capitis
- Tinea corporis
- Tinea pedis
- Trametinib
- Transient acantholytic dermatosis
- Treponema pallidum
- Trichinosis
- Trichomoniasis
- Trigeminal trophic syndrome
- Trimethoprim
- Trypanosomiasis
- Tungiasis
- Urticaria
- Urushiol
- Uveal diseases
- Uveal melanoma
- Uveitis
- Vaginitis
- Vasculitis
- Vernal keratoconjunctivitis
- Vibratory angioedema
- Vitamin a
- Vulvar cancer
- Wells syndrome
- West african trypanosomiasis
- Wiskott-aldrich syndrome
- Xanthogranulomatous cholecystitis
- Xerosis
- X-linked ichthyosis
# History and Symptoms
- Include medical and family history, exposure history, sexual history
# Physical Examination
- Complete system evaluation can detect underlying diseases
## Abdomen
- Stool exam (blood)
- Pap smear & pelvic
# Laboratory Findings
- Labs include
- CBC with differential
- LFTs
- renal function
- thyroid function tests
- HIV test
- Hepatitis B & Hepatitis C
- Serum iron
- Serum urine protein
- Stool for parasites
# Treatment
A variety of over-the-counter and prescription anti-itch drugs are available. Some plant products have been found to be effective anti-pruritics, others not. Non-chemical remedies include cooling, warming, soft stimulation.
Sometimes scratching relieves isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching can intensify itching and even cause further damage to the skin, dubbed the "itch-scratch-itch cycle".
The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients.
# Sensations Associated with Scratching
Pain and itch have very different behavioral response patterns. Pain evokes a withdrawal reflex which leads to retraction and therefore a reaction trying to protect an endangered part of the body. Itch creates a scratching reflex which draws one to the affected skin site. For example, responding to a local itch sensation is an effective way to remove insects on the skin. Scratching has traditionally been regarded as a way to relieve one self by reducing the annoying itch sensation. However there are hedonic aspects of scratching as one would find noxious scratching highly pleasurable. This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until it no longer produces a pleasant or painful sensation instead of when the itch sensation disappears. It has been hypothesized that motivational aspects of scratching include the frontal brain areas of reward and decision making. These aspects might therefore contribute to the compulsive nature of itch and scratching.
## Contagious Itch
Events of “contagious itch” are very common occurrences. Even a discussion on the topic of itch can give one the desire to scratch. Itch is likely more than a localized phenomenon in the place we scratch. Results from a recent study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching. There is currently little detailed data on central activation for contagious itching but it is hypothesized that a human mirror neuron system exists in which we imitate certain motor actions when we view others performing the same action. A similar phenomenon in which mirror neurons are used to explain the cause is contagious yawning. | Pruritis
For patient information click here
Template:DiseaseDisorder infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2] Kiran Singh, M.D. [3] Luke Rusowicz-Orazem, B.S.
# Overview
Itch (Latin: pruritus) is defined as an unpleasant sensation that evokes the desire or reflex to scratch. Itch has many similarities to pain and both are unpleasant sensory experiences but their behavioral response patterns are different. Pain creates a reflex withdrawal while itch leads to a scratch reflex.[1] Unmyelinated nerve fibers for itch and pain both originate in the skin, however information for them are conveyed centrally in two distinct systems that both use the same peripheral nerve bundle and spinothalamic tract.[2]
Historically, the sensations of itch and pain have not been considered to be independent of each other until recently where it was found that itch has several features in common with pain but exhibits notable differences.[3] The physiological mechanisms of itch are currently poorly understood and this is mainly due to the lack of animal models of itch. Pruritic stimuli mostly create the same reactions as noxious stimuli in experimental animals, but humans are capable of discerning the distinct features of itch and pain. Therefore human studies have provided most of the information regarding the processing of pruritic stimuli.[4]
# Mechanism
Itch can originate in the peripheral nervous system (dermal or neuropathic) or in the central nervous system (neuropathic, neurogenic, or psychogenic).[5]
## Dermal/Pruritoceptive
Itch originating in the skin is considered pruritoceptive and can be induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation. The primary afferent neurons responsible for histamine induced itch are unmyelinated C-fibers. In human C-fiber nociceptors, two major classes exist: mechano-responsive nociceptors and mechano-insensitive nociceptors. Mechano-responsive nociceptors have been in shown in studies to respond to mostly pain and mechano-insensitive receptors respond mostly to itch induced by histamine. However it does not explain mechanically induced itch or when itch is produced without a flare reaction which involves no histamine. Therefore it is possible that pruritoceptive nerve fibers have different classes of fibers, which is currently unclear in current research.[1]
Studies have been done to show that itch receptors are only found on the top two skin layers, the epidermis and the epidermal/dermal transition layers. Shelley and Arthur had verified the depth by injecting individual itch powder spicules (Mucuna pruriens) and found that maximal sensitivity was found at the basal cell layer or the innermost layer of the epidermis. Surgical removal of those skin layers removed the ability for a patient to perceive itch. Itch is never felt in muscle, joints, or inner organs, which show that deep tissue does not contain itch signaling apparatuses.[3]
Sensitivity to puritic stimuli is not even across the skin and has a random spot distribution with similar density to that of pain. The same substances that elicit itch upon intracutaneous injection (injection within the skin) elicit only pain when injected subcutaneously (beneath the skin). Itch is readily abolished in skin areas treated with nociceptor excitotoxin capsaicin but remains unchanged in skin areas which were rendered touch-insensitive by pretreatment with saponins, an anti-inflammatory agent. Although experimentally induced itch can still be perceived under a complete A-fiber conduction block, it is significantly diminished. Overall, itch sensation is mediated by A-delta and C nociceptors located in the uppermost layer of the skin.[6]
## Neuropathic
Neuropathic itch can originate at any point along the afferent pathway as a result of damage of the nervous system. They could include diseases or disorders in the central nervous system or peripheral nervous system.[3] Examples of neuropathic itch in origin are nostalgia paresthetica, brachioradial pruritus, brain tumors, multiple sclerosis, peripheral neuropathy, and nerve irritation.[7]
## Neurogenic
Neurogenic itch, which is itch induced centrally but with no neural damage, is often associated with increased accumulation of endogenous opioids and possibly synethetic opioids.[3]
## Psychogenic
Itch is also associated with some psychiatric disorders such as delusions of parasitosis or related obsessive-compulsive disorders, for example neurotic scratching.[3]
# Interactions between Itch and Pain
## Pain Inhibits Itch
The sensation of itch can be reduced by many painful sensations. Many studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat, physical rubbing/scratching, noxious chemicals, and electric shock. Any stimuli that causes pain will inhibit itching.
The inhibition of itch by painful stimuli, including heat, physical stimulus, and chemical stimulus, has been shown experimentally. In an article written by Louise Ward and others, they studied the effects of noxious and non-noxious counterstimuli, such as heat, physical vibration, or chemical stimulation on skin, in healthy adults after they had experimentally induced itch (transdermal iontophoresis of histamine) and pain (with topical mustard oil) in their skin. They found that when they induced non-noxious counterstimuli, the reduction of pain and itch was reduced only for up to 20 seconds. However when they induced noxious counterstimuli, there was a significant inhibition of itch for an extended period of time but no inhibition of pain. In addition, it was found that brief noxious stimuli created an anti-itch state for more than 30 minutes. These findings show that itch is not a subliminal form of pain and that noxious counterstimulus is likely to act through a central instead of a peripheral mechanism.[4]
Painful electrical stimulation reduced histamine-induced itch for several hours at a distance up to 10 cm from the stimulated site, which suggests a central mode of action. A new method had been recently found, by Hans-Jorgen Nilsson and others, that is able to relieve itch without damaging the skin called cutaneous field stimulation (CFS). CFS consists of a flexible rubber plate with 16 needle-like electrodes placed regularly at 2-centimeter intervals in a 4 by 4 matrix used to electrically stimulate nerve fibers in the surface of the skin. The electrodes were stimulated continuously at 4 Hertz per electrode, pulse duration of 1 millisecond, intensity 0.4-0.8 milliamperes, and for 25 minutes. CFS resulted in a pricking and burning sensation that usually faded away very quickly. The burning sensation was still present during a selective block of impulse conduction of A-fibers in myelinated fibers indicating that nociceptive C-fibers are activated by CFS. In addition, a flare reaction had been noted to develop around the CFS electrodes which indicate activation of axon reflexes in nociceptive C-fibers. Itch, which was induced by transdermal iontophoresis of histamine, was inhibited within the skin area treated with CFS, and it was reduced 10 cm distally to a significant amount. CFS proves to offer a new method of combating itch by using painful electrical stimulation as it creates a long lasting inhibitory effect, does not create any significant skin injuries, and is simple to manage. It is able to activate powerful itch inhibitory mechanisms possibly routed through central mechanisms, which could normally be activated by scratching of the skin.[8]
A study done by Gil Yosipovitch, Katharine Fast, and Jeffrey Bernhard showed that noxious heat and scratching was able to inhibit or decrease itch induced by transdermal iontophoresis of histamine and most interestingly, decrease skin blood flow. Twenty-one healthy volunteers participated in their study. Baseline measurements of skin blood flow were obtained on the flexor part of the forearm and then compared with skin blood flow after various stimuli. Then transdermal iontophoresis of histamine was performed and tested with various stimuli. It is well known that skin blood flow is significantly increased during mechanical scratching, warming, and noxious heat. However it is quite interesting that this study is the first to examine the changes of blood flow by stimuli during iontophoresis of histamine and how itch is perceived in those conditions. Its examination provided an unexpected result that noxious heat and scratching has an inhibitory effect.[9]
A negative correlation was found between pain sensitivity and itch sensitivity. In a study done by Amanda Green and others, they aimed to determine itch-related genetic factors, and establish a more useful animal model for itch. They looked at 11 different inbred mouse strains and compared their scratching behavior in response to two itch inducing agents, histamine and chloroquine. Every strain revealed an inverted-U shape dose response relationship from chloroquine, indicating that moderate dosages produced more scratching than at higher dosages. An explanation is that higher dosage produces more pain and the presence of pain inhibits pain thereby lowering the amount of overall scratching. Another notable result was that histamine induced scratching occurred in female mice on average 23% more than males. Finally, it was found that mice having strains sensitive to pain were resistant to itch and vice versa.[10]
## Peripheral Sensitization
Inflammatory mediators such as bradykinin, serotonin (5-HT) and prostaglandins, released during a painful or pruritic inflammatory condition not only activates pruriceptors but also causes acute sensitization of the nociceptors. In addition, expression of neuro growth factors (NGF) can cause structural changes in of nociceptors such as sprouting. NGF is high in injured or inflamed tissue. Increased NGF is also found in atopic dermatitis, a hereditary and non-contagious skin disease with chronic inflammation.[11] NGF is known to up-regulate neuropeptides, especially substance P. Substance P has been found to have an important role in inducing pain however there is no confirmation that substance P directly causes acute sensitization. Instead substance P may contribute to itch by increasing neuronal sensitization and may the affect release of mast cells, which contain many granules rich in histamine, during long-term interaction.[1]
## Central Sensitization
Noxious input to the spinal cord is known to produce central sensitization, which consists of allodynia, exaggeration of pain, and punctuate hyperalgesia, extreme sensitivity to pain. Two types of mechanical hyperalgesia can occur: 1) touch that is normally painless in the uninjured surroundings of a cut or tear can trigger painful sensations (touch-evoked hyperalgesia), and 2) a slightly painful pin prick stimulation is perceived as more painful around a focused area of inflammation (punctuate hyperalgesia). Touch-evoked hyperalgesia requires continuous firing of primary afferent nociceptors, and punctuate hyperalgesia does not require continuous firing which means it can persist for hours after a trauma and can be stronger than normally experienced. In addition, it was found that patients with neuropathic pain, histamine ionophoresis resulted in a sensation of burning pain rather than itch, which would be induced in normal healthy patients. This shows that there is spinal hypersensitivity to C-fiber input in chronic pain.[1]
# Causes
## Common Causes
- Xerosis
- Eczema
- Psoriasis
- Sunburn
- Athlete's foot
- Insect bites
- Urushiol
- Hodgkin's disease
- Jaundice
- Polycythemia
- Scabies
- Lice
- Thyroid illness
- Shaving
- Diabetes Mellitus
- Dandruff
- Iron deficiency anemia
- Parasitic infections
- Allergies
- Morphine
- Terbinafine
- Niacin
- Simvastatin
- Cholestasis
## Causes by Organ System
## Causes in Alphabetical Order
- Acamprosate
- Acanthocheilonemiasis
- Acipimox
- Acrodermatitis chronica atrophicans
- Acrokeratosis paraneoplastica of bazex
- Acropustulosis of infancy
- Actinic granuloma
- Adrenergic conditions
- Aging
- Aids
- Alfentanil
- Allergic conjunctivitis
- Allergies
- Allopurinol
- Altretamine
- Amphetamine
- Amyloidosis
- Ancylostoma duodenale
- Angioedema
- Ascariasis
- Athlete's foot
- Atopic dermatitis
- Bacterial conjunctivitis
- Bile acid synthesis defects
- Blood transfusion and complications
- Brachioradial pruritus
- Brain abscess
- Bullous pemphigoid
- Burn wounds
- Candida albicans
- Carbimazole
- Carcinoid syndrome
- Cerebrovascular accidents
- Chilblains
- Chloroquine
- Cholestasis
- Cholestatic jaundice
- Cholinergic conditions
- Chronic eosinophilic leukemia
- Chronic fatigue syndrome
- Chronic hepatitis
- Chronic lymphocytic leukemia
- Chronic myringitis
- Cilostazol
- Cimex lectularius
- Ciprofloxacin
- Cocaine use
- Conjunctivitis
- Connective tissue diseases
- Contact dermatitis
- Creutzfeldt-jakob disease
- Cutaneous larva migrans
- Cutaneous t-cell lymphoma
- Dandruff
- Decompression sickness
- Delusional parasitosis
- Dermatitis artefacta
- Dermatitis herpetiformis
- Dermatomyositis
- Dermatophytosis
- Diabetes mellitus
- Diamino diphenylmethane
- Diffuse systemic sclerosi
- Dracunculiasis
- Drug side effect
- Drug-induced liver disease
- Dumping syndrome
- Eczema
- Elastosis perforans serpiginosa
- Eosinophilia-myalgia syndrome
- Erythema annulare centrifugum
- Erythroderma
- Erythropoietic protoporphyria
- Essential thrombocythemia
- Fabry disease
- Familial cold urticaria
- Fibromyalgia
- Fixed drug eruption
- Fox-fordyce disease
- Functional disorders
- Gestational pemphigoid
- Gnathostomiasis
- Gold salts
- Hemochromatosis
- Hepatitic c
- Hepatobiliary disease
- Hepatoma
- Herpes gestationis
- Herpes simplex
- Herpes virus 2
- Herpes zoster
- Hidradenitis suppurativa
- Hiv
- Hodgkin's disease
- Hodgkin's lymphoma
- Hookworms
- Hymenolepiasis
- Hypereosinophilic syndrome
- Hyperimmunoglobulin e (ige) syndrome
- Hyperparathyroidism
- Hyperthyroidism
- Hypoparathyroidism
- Hypothyroidism
- Id reaction
- Imipenem
- Inflammatory linear verrucous epidermal nevus
- Insect bites
- Interleukin 2
- Intrahepatic cholestasis of pregnancy
- Iron deficiency
- Jaundice
- Kerion
- Ketoconazole
- Kraurosis vulvae
- Lamellar ichthyosis
- Latex allergies
- Leptospirosis
- Leukemia
- Leukemia cutis
- Lice
- Lichen aureus
- Lichen planus
- Lichen sclerosus et atrophicus
- Lichen simplex chronicus
- Lichen striatus
- Liver cancer
- Liver failure
- Louse-borne diseases
- Lymphatic filariasis
- Macrophage activation syndrome
- Malassezia furfur
- Malignancy
- Mansonelliasis
- Mastocytosis
- Medication side effects
- Mefloquine
- Melanoma
- Mercury
- Meropenem
- Metastatic liver cancer
- Methimazole
- Methionine
- Miliaria rubra
- Mite conditions
- Morphine
- Morphoea
- Multiple endocrine neoplasia
- Multiple sclerosis
- Myelodysplastic syndrome
- Necator americanus
- Necitumumab
- Nephrogenic fibrosing dermopathy
- Neurofibromatosis
- Niacin
- Niclosamide
- Nicotinic acid
- Non-hodgkin's lymphoma
- Norfloxacin
- Notalgia paraesthetica
- Nummular dermatitis
- Obeticholic acid
- Occupational cancer
- Onchocerciasis
- Opioid use
- Palifermin
- Pancreatic islet cell cancer
- Papilloma
- Paraneoplastic syndrome
- Parasitophobia
- Parvoviral infection
- Peanut allergies
- Pediculosis
- Pediculus humanus capitis
- Pediculus humanus corporis
- Pellagra
- Pemphigoid gestationis
- Pemphigus foliaceus
- Penicillin allergy
- Permethrin
- Pfic
- Phaeohyphomycosis
- Photodermatitis
- Phthiriasis
- Pinworms
- Pityriasis alba
- Pityriasis rosea
- Pollen allergy
- Polycythemia rubra vera
- Polycythemiaistamine
- Polymorphic eruption of pregnancy
- Polymorphic light eruption
- Pompholyx
- Portal hypertension
- Postherpetic neuralgia
- Pregnancy
- Primary cutaneous amyloidosis
- Primary sclerosing cholangitis
- Propylthiouracil
- Prurigo nodularis
- Psoriasis
- Psychogenic excoriation
- Pulex irritans
- Rabies
- Remifentanil
- Renal disease
- Renal failure
- Rhabditida infections
- Rhesus isoimmunisation
- Sarcoidosis
- Sarcoptes scabiei
- Scabies
- Scars
- Schamberg's disease
- Scleroderma
- Secernentea infections
- Shaving
- Shingles
- Siltuximab
- Simeprevir
- Simvastatin
- Sjögren syndrome
- Skin allergies
- Skin conditions
- Skin rash
- Sleeping sickness
- Small-fiber neuropathies
- Starvation
- Strongyloidiasis
- Sufentanil
- Sunburn
- Swimmer's itch
- Symptomatic dermatographism
- Systemic lupus erythematosus
- Taeniasis
- Terbinafine
- Threadworm
- Thyroid disease
- Tinea capitis
- Tinea corporis
- Tinea pedis
- Trametinib
- Transient acantholytic dermatosis
- Treponema pallidum
- Trichinosis
- Trichomoniasis
- Trigeminal trophic syndrome
- Trimethoprim
- Trypanosomiasis
- Tungiasis
- Urticaria
- Urushiol
- Uveal diseases
- Uveal melanoma
- Uveitis
- Vaginitis
- Vasculitis
- Vernal keratoconjunctivitis
- Vibratory angioedema
- Vitamin a
- Vulvar cancer
- Wells syndrome
- West african trypanosomiasis
- Wiskott-aldrich syndrome
- Xanthogranulomatous cholecystitis
- Xerosis
- X-linked ichthyosis
# History and Symptoms
- Include medical and family history, exposure history, sexual history
# Physical Examination
- Complete system evaluation can detect underlying diseases
## Abdomen
- Stool exam (blood)
- Pap smear & pelvic
# Laboratory Findings
- Labs include
- CBC with differential
- LFTs
- renal function
- thyroid function tests
- HIV test
- Hepatitis B & Hepatitis C
- Serum iron
- Serum urine protein
- Stool for parasites
# Treatment
A variety of over-the-counter and prescription anti-itch drugs are available. Some plant products have been found to be effective anti-pruritics, others not. Non-chemical remedies include cooling, warming, soft stimulation.
Sometimes scratching relieves isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching can intensify itching and even cause further damage to the skin, dubbed the "itch-scratch-itch cycle".
The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients.
# Sensations Associated with Scratching
Pain and itch have very different behavioral response patterns. Pain evokes a withdrawal reflex which leads to retraction and therefore a reaction trying to protect an endangered part of the body. Itch creates a scratching reflex which draws one to the affected skin site. For example, responding to a local itch sensation is an effective way to remove insects on the skin. Scratching has traditionally been regarded as a way to relieve one self by reducing the annoying itch sensation. However there are hedonic aspects of scratching as one would find noxious scratching highly pleasurable.[1] This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until it no longer produces a pleasant or painful sensation instead of when the itch sensation disappears.[12] It has been hypothesized that motivational aspects of scratching include the frontal brain areas of reward and decision making. These aspects might therefore contribute to the compulsive nature of itch and scratching.[1]
## Contagious Itch
Events of “contagious itch” are very common occurrences. Even a discussion on the topic of itch can give one the desire to scratch. Itch is likely more than a localized phenomenon in the place we scratch. Results from a recent study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching. There is currently little detailed data on central activation for contagious itching but it is hypothesized that a human mirror neuron system exists in which we imitate certain motor actions when we view others performing the same action. A similar phenomenon in which mirror neurons are used to explain the cause is contagious yawning.[1] | https://www.wikidoc.org/index.php/Ddx:Pruritis | |
98d0d5e2fa7345047ee58adaabcf56260f42b529 | wikidoc | Tinnitus | Tinnitus
# Overview
Tinnitus is derived from the Latin word tinnire, meaning to ring. Tinnitus can be classified as subjective and objective. This classification not only explains the underlying etiology but also directs the management of tinnitus. In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain. Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model. Common causes of tinnitus include Ototoxicity, Presbycusis, noise induced hearing loss, late onset congenital hearing loss, meniere's disease, and Loop diuretics. The incidence rate of tinnitus increases with age and is more prevalent in older people. Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers. If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression. TSI is used to rank the patient's based upon their severity. The score ranges from 0-45. Symptoms and history include sounds such as ringing, buzzing, pulsatile, roaring and humming and progressive hearing loss. An extensive neurological examination may rule out underlying brainstem damage or hearing loss. The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal. MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed. Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem. These tests include: pure-tone audiogram, tympanometry, auditory reflex testing, determination of speech discrimination abilities, otoacoustic emissions testing and auditory brainstem response testing (ABR). Tinnitus is a symptom and not a disease itself. It is a chronic condition that can be managed by treating the underlying etiology. The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus. It is usually achieved by identifying the underlying pathology or the associated disease. It is recommended to treat underlying insomnia and depression (Grade 1B). Cochlear implants may be considered for tinnitus associated with severe sensorineural hearing loss. Other therapies include: tinnitus retraining therapy (TRT) (Grade 1C), biofeedback (Grade 2C), and cognitive behavioral therapy (CBT) as an adjunct to TRT (Grade 2C). Acupuncture and electrical stimulation are considered equally effective as placebo, no significant role established so far.
# Historical Perspective
- In the early 19th century, Frenchman and Jean Marie Gaspard Itard introduced the concept of masking. They were the first ones to differentiate between subjective and objective tinnitus.
- Later in the 19th Century, with the introduction of germ theory and anesthesia, surgical therapy such as incudectomy was established.
- Tinnitus is derived from the Latin word tinnire, meaning to ring.
# Classification
Tinnitus can be classified as subjective and objective. This classification not only explains the underlying etiology but also directs the management of tinnitus.
## Subjective tinnitus:
- It is only experienced by the affected individual in the absence of any auditory stimulation
- More common, usually described as continuous ringing, high pitch sound
## Objective tinnitus:
- It is experienced not only by the affected individual but also by anyone else
- Relative rare, usually described as intermittent venous hum, low pitch sound
- It has an underlying vascular (abnormality of the carotid artery, jugular bulb or jugular vein) or muscular etiology (degenerative conditions such as amyotrophic lateral sclerosis) and usually caused by sound produced in ear, head or neck.
# Pathophysiology
In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain. Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model.
### Lesion projection zone (LPZ):
This zone is defined as the area in the auditory cortex that represents the damaged cochlear input. The neurons in the LPZ zone show 2 main changes:
- Accelerated spontaneous firing rate
- Increased representation of neurons that represent the damaged cochlear region also known as lesion edge frequencies in the LPZ
## Tinnitus model:
This model explains 2 major phenomena in the auditory cortex caused by lack of sensory peripheral auditory input (cochlea)
- Hyperactivity in the lesion projections zone (LPZ)
- Increased cortical representation of the lesion-edge frequencies in the LPZ
# Causes of subjective tinnitus
### Sensorineural hearing loss:
- Ototoxicity
- Presbycusis
- Noise induced hearing loss
- Late onset congenital hearing loss
- Idiopathic
### Cochlear injury:
- Meniere's disease
- Loop diuretics
- Platinum based chemotherapy
- Antibiotics
- Salicylate
- Trauma
### Vascular causes:
- Systemic hypertension
- Sickle cell anemia
- Small vessel disease
- Hypercholesterolemia
- Hypercoagulable state
- Diabetic vasculopathy
### CNS causes:
- Pseudotumor cerebri
- Stroke
- Vascular malformations
- Tumor
- Sarcoid
- Multiple sclerosis
### Infections:
- Rubella
- Cytomegalovirus
- Chronic otitis media
- Neurosyphilis
- Measles
- Lyme disease
- Meningitis
### Bone disease:
- Otosclerosis
- Fibrous dysplasia
- Osteogenesis imperfecta
- Paget's disease
### Metabolic disorders:
- Hyperparathyroidism
- Chronic renal failure
- Diabetes mellitus
- Thyroid disease
### Autoimmune diseases:
- Autoimmune inner ear disease
- SLE
- Rheumatoid arthritis
### Medications:
- ACE inhibitors
- Antimalarial medications
- Aminoglycosides
- Dapsone
- Doxazosin
- Calcium channel blockers
- Benzodiazepines
- Cisplatin
- Clarithromycin
- COX-2 inhibitors
- Loop diuretics
- Tricyclic antidepressant
# Differential Diagnosis of Tinnitus
ABBREVIATIONS
VZV= Varicella zoster virus, MRI= Magnetic resonance imaging, ESR= Erythrocyte sedimentation rate, EEG= Electroencephalogram, CSF= Cerebrospinal fluid, GPe= Globus pallidus externa, ICHD= International Classification of Headache Disorders
# Epidemiology and Demographics
- Tinnitus affects 10 to 15% of the population.
- 85% of the population presenting with ear symptoms/disorders report tinnitus as an associated symptom.
- The incidence rate of tinnitus increases with age and is more prevalent in older people.
- Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers.
# Risk Factors
Common risk factors of tinnitus include
- Age
- Sensorineural hearing loss
- Loud noise exposure
- Vestibular schwannoma
- Ototoxic medication
- History of anxiety and depression
- History of head trauma
- History of multiple sclerosis
# Natural History, Complications and Prognosis
- Early clinical features may include ear fullness, huming or ringing sensations in the ear
- If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression.
# Diagnosis
## Diagnostic criteria:
### Tinnitus severity index (TSI)
- TSI is used to rank the patient's based upon their severity
- The score ranges from 0-45
### Tinnitus handicap questionnaire:
- This questionnaire includes 27 questions and is used to estimate the social, physical and emotional handicap severity
### Tinnitus handicap inventory:
- This questionnaire has 4 categories to classify severity
- None, mild, moderate, and severe.
## History and Symptoms:
- Sounds such as ringing, buzzing, pulsatile, roaring and humming
- Progressive hearing loss
- Recent exposure to excessive or loud noise or head trauma
- Poor hygiene leading to cerumen impaction
- Ear pain
- History of certain medication exposure
## Physical Examination:
- The ear examination may show signs of cerumen impaction, underlying infection or tympanic membrane perforation.
- Auscultation of neck, orbits and periauricular areas as helpful in establishing the diagnosis of vascular causes
- An extensive neurological examination may rule out underlying brainstem damage or hearing loss
- The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal.
## Laboratory Findings:
- There are no specific lab findings associated with tinnitis.
## Imaging:
- MRA and CTA are the gold standard diagnostic tests for arteriovenous fistula related tinnitus.
- MRI with contrast is the initial preferred diagnostic test of choice for suspected vascular tinnitus.
- MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed.
## Other Diagnostic Testing:
- Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem. These tests include:
Pure-tone audiogram
Tympanometry
Auditory reflex testing
Determination of speech discrimination abilities
Otoacoustic emissions testing
Auditory brainstem response testing (ABR)
- Pure-tone audiogram
- Tympanometry
- Auditory reflex testing
- Determination of speech discrimination abilities
- Otoacoustic emissions testing
- Auditory brainstem response testing (ABR)
# Treatment
- Tinnitus is a symptom and not a disease itself. It is a chronic condition that can be managed by treating the underlying etiology.
- The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus. It is usually achieved by identifying the underlying pathology or the associated disease.
- It is recommended to treat underlying insomnia and depression. (Grade 1B)
## Medical Therapy
Following medications have minimal to modest role in relieving tinnitus.
- Misoprostol
- Lidocaine (intratympanic or intravenous)
- Benzodiazepine (alprazolam)
- Steroids such as dexamethasone (intratympanic)
- Carbamazepine
Following medications have been studied for tinnitus but are not found to be effective and have no role in the treatment of tinnitus
- Anticonvulsants
- Melatonin
- Ginkgo biloba
- Niacin
## Surgery
- Cochlear implants may be considered for tinnitus associated with severe sensorineural hearing loss.
## Other therapies:
- Tinnitus retraining therapy (TRT) (Grade 1C)
- Biofeedback (Grade 2C)
- Cognitive behavioral therapy (CBT) as an adjunct to TRT (Grade 2C)
- Acupuncture and electrical stimulation are considered equally effective as placebo, no significant role established so far.
## Prevention
- Tinnitus may be been prevented by limiting the exposure to loud noise. | Tinnitus
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2] Sabeeh Islam, MBBS[3]
# Overview
Tinnitus is derived from the Latin word tinnire, meaning to ring. Tinnitus can be classified as subjective and objective. This classification not only explains the underlying etiology but also directs the management of tinnitus. In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain. Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model. Common causes of tinnitus include Ototoxicity, Presbycusis, noise induced hearing loss, late onset congenital hearing loss, meniere's disease, and Loop diuretics. The incidence rate of tinnitus increases with age and is more prevalent in older people. Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers. If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression. TSI is used to rank the patient's based upon their severity. The score ranges from 0-45. Symptoms and history include sounds such as ringing, buzzing, pulsatile, roaring and humming and progressive hearing loss. An extensive neurological examination may rule out underlying brainstem damage or hearing loss. The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal. MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed. Initial audiometric tests are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem. These tests include: pure-tone audiogram, tympanometry, auditory reflex testing, determination of speech discrimination abilities, otoacoustic emissions testing and auditory brainstem response testing (ABR). Tinnitus is a symptom and not a disease itself. It is a chronic condition that can be managed by treating the underlying etiology. The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus. It is usually achieved by identifying the underlying pathology or the associated disease. It is recommended to treat underlying insomnia and depression (Grade 1B). Cochlear implants may be considered for tinnitus associated with severe sensorineural hearing loss. Other therapies include: tinnitus retraining therapy (TRT) (Grade 1C), biofeedback (Grade 2C), and cognitive behavioral therapy (CBT) as an adjunct to TRT (Grade 2C). Acupuncture and electrical stimulation are considered equally effective as placebo, no significant role established so far.
# Historical Perspective
- In the early 19th century, Frenchman and Jean Marie Gaspard Itard introduced the concept of masking. They were the first ones to differentiate between subjective and objective tinnitus.
- Later in the 19th Century, with the introduction of germ theory and anesthesia, surgical therapy such as incudectomy was established.
- Tinnitus is derived from the Latin word tinnire, meaning to ring.
-
# Classification
Tinnitus can be classified as subjective and objective. This classification not only explains the underlying etiology but also directs the management of tinnitus.
## Subjective tinnitus:
- It is only experienced by the affected individual in the absence of any auditory stimulation
- More common, usually described as continuous ringing, high pitch sound
## Objective tinnitus:
- It is experienced not only by the affected individual but also by anyone else
- Relative rare, usually described as intermittent venous hum, low pitch sound
- It has an underlying vascular (abnormality of the carotid artery, jugular bulb or jugular vein) or muscular etiology (degenerative conditions such as amyotrophic lateral sclerosis) and usually caused by sound produced in ear, head or neck.
# Pathophysiology
In the normal functioning auditory pathway, there is ordered tonotopic frequency mapping from the cochlea to the auditory cortex via midbrain.[1][2] Conditions associated with cochlear damage result in altered tonotopic organization and ultimately tinnitus. The pathophysiology of tinnitus can be explained by the tinnitus model.[3][4]
### Lesion projection zone (LPZ):
This zone is defined as the area in the auditory cortex that represents the damaged cochlear input. The neurons in the LPZ zone show 2 main changes:
- Accelerated spontaneous firing rate
- Increased representation of neurons that represent the damaged cochlear region also known as lesion edge frequencies in the LPZ
## Tinnitus model:
This model explains 2 major phenomena in the auditory cortex caused by lack of sensory peripheral auditory input (cochlea)
- Hyperactivity in the lesion projections zone (LPZ)
- Increased cortical representation of the lesion-edge frequencies in the LPZ
# Causes of subjective tinnitus
### Sensorineural hearing loss:
- Ototoxicity
- Presbycusis
- Noise induced hearing loss
- Late onset congenital hearing loss
- Idiopathic
### Cochlear injury:
- Meniere's disease
- Loop diuretics
- Platinum based chemotherapy
- Antibiotics
- Salicylate
- Trauma
### Vascular causes:
- Systemic hypertension
- Sickle cell anemia
- Small vessel disease[5][6]
- Hypercholesterolemia
- Hypercoagulable state
- Diabetic vasculopathy
### CNS causes:
- Pseudotumor cerebri
- Stroke
- Vascular malformations
- Tumor
- Sarcoid
- Multiple sclerosis
### Infections:
- Rubella
- Cytomegalovirus
- Chronic otitis media
- Neurosyphilis
- Measles
- Lyme disease
- Meningitis
### Bone disease:
- Otosclerosis
- Fibrous dysplasia
- Osteogenesis imperfecta
- Paget's disease
### Metabolic disorders:
- Hyperparathyroidism
- Chronic renal failure
- Diabetes mellitus
- Thyroid disease
### Autoimmune diseases:
- Autoimmune inner ear disease
- SLE
- Rheumatoid arthritis
### Medications:
- ACE inhibitors
- Antimalarial medications
- Aminoglycosides
- Dapsone
- Doxazosin
- Calcium channel blockers
- Benzodiazepines
- Cisplatin
- Clarithromycin
- COX-2 inhibitors
- Loop diuretics
- Tricyclic antidepressant
# Differential Diagnosis of Tinnitus
ABBREVIATIONS
VZV= Varicella zoster virus, MRI= Magnetic resonance imaging, ESR= Erythrocyte sedimentation rate, EEG= Electroencephalogram, CSF= Cerebrospinal fluid, GPe= Globus pallidus externa, ICHD= International Classification of Headache Disorders
# Epidemiology and Demographics
- Tinnitus affects 10 to 15% of the population.
- 85% of the population presenting with ear symptoms/disorders report tinnitus as an associated symptom.[7]
- The incidence rate of tinnitus increases with age and is more prevalent in older people.[8]
- Tinnitus is more prevalent in men compared to women and smokers compared to non-smokers.[9][10]
# Risk Factors
Common risk factors of tinnitus include
- Age
- Sensorineural hearing loss
- Loud noise exposure
- Vestibular schwannoma
- Ototoxic medication
- History of anxiety and depression
- History of head trauma
- History of multiple sclerosis
# Natural History, Complications and Prognosis
- Early clinical features may include ear fullness, huming or ringing sensations in the ear
- If left untreated, patients may progress to functional impairment, insomnia, anxiety, and depression.[11]
# Diagnosis
## Diagnostic criteria:
### Tinnitus severity index (TSI)
- TSI is used to rank the patient's based upon their severity
- The score ranges from 0-45
### Tinnitus handicap questionnaire:
- This questionnaire includes 27 questions and is used to estimate the social, physical and emotional handicap severity
### Tinnitus handicap inventory:
- This questionnaire has 4 categories to classify severity
- None, mild, moderate, and severe.
## History and Symptoms:
- Sounds such as ringing, buzzing, pulsatile, roaring and humming
- Progressive hearing loss
- Recent exposure to excessive or loud noise or head trauma
- Poor hygiene leading to cerumen impaction
- Ear pain
- History of certain medication exposure
## Physical Examination:
- The ear examination may show signs of cerumen impaction, underlying infection or tympanic membrane perforation.
- Auscultation of neck, orbits and periauricular areas as helpful in establishing the diagnosis of vascular causes
- An extensive neurological examination may rule out underlying brainstem damage or hearing loss
- The Weber and Rinne test are done to establish sensorineural or conductive hearing loss. They are usually abnormal.
## Laboratory Findings:
- There are no specific lab findings associated with tinnitis.
## Imaging:
- MRA and CTA are the gold standard diagnostic tests for arteriovenous fistula related tinnitus.
- MRI with contrast is the initial preferred diagnostic test of choice for suspected vascular tinnitus.
- MRI with contrast is followed by CT/CTA and ultimately interventional angiography, if needed.[12]
## Other Diagnostic Testing:
- Initial audiometric tests[13] are done to identify asymmetries between the ears and to locate the site of abnormality such as middle ear, cochlea, and brainstem. These tests include:
Pure-tone audiogram
Tympanometry
Auditory reflex testing
Determination of speech discrimination abilities
Otoacoustic emissions testing
Auditory brainstem response testing (ABR)
- Pure-tone audiogram
- Tympanometry
- Auditory reflex testing
- Determination of speech discrimination abilities
- Otoacoustic emissions testing
- Auditory brainstem response testing (ABR)
# Treatment
- Tinnitus is a symptom and not a disease itself. It is a chronic condition that can be managed by treating the underlying etiology.
- The treatment of tinnitus is usually directed towards improvement in the quality of life by decreasing awareness or desensitizing towards tinnitus. It is usually achieved by identifying the underlying pathology or the associated disease.
- It is recommended to treat underlying insomnia and depression. (Grade 1B)
## Medical Therapy
Following medications have minimal to modest role in relieving tinnitus.
- Misoprostol
- Lidocaine (intratympanic or intravenous)
- Benzodiazepine (alprazolam)
- Steroids such as dexamethasone (intratympanic)
- Carbamazepine
Following medications have been studied for tinnitus but are not found to be effective and have no role in the treatment of tinnitus
- Anticonvulsants
- Melatonin
- Ginkgo biloba
- Niacin
## Surgery
- Cochlear implants may be considered for tinnitus associated with severe sensorineural hearing loss.
## Other therapies:
- Tinnitus retraining therapy (TRT) (Grade 1C)
- Biofeedback (Grade 2C)
- Cognitive behavioral therapy (CBT) as an adjunct to TRT (Grade 2C)
- Acupuncture and electrical stimulation are considered equally effective as placebo, no significant role established so far.
## Prevention
- Tinnitus may be been prevented by limiting the exposure to loud noise. | https://www.wikidoc.org/index.php/Ddx:Tinnitus | |
43f3edb72b3b6206efd83bfae4d18d2ae2d12fbe | wikidoc | Xanthoma | Xanthoma
Synonyms and keywords: Xanthoma, xanthomata, xanthomatosis
# Overview
A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis), from Greek xanthos, ξανθος, "yellow", is a deposition of yellowish cholesterol-rich material in tendons or other body parts in various disease states. They are cutaneous manifestations of lipidosis in which there is an accumulation of lipids in large foam cells within the skin.
They are associated with hyperlipidemias, both primary and secondary types.
Tendon Xanthoma are associated with Type II hyperlipidaemia and chronic biliary obstruction.
Palmar xanthomata and tuboeruptive xanthomata (over knees and elbows) occur in Type III hyperlipidaemia
# Causes
## Common causes of Xanthomas
- Hypercholesterolemia
- Hyperchylomicronemia
- Hyperlipidaemia
- Hyperlipoproteinemia
## Causes by Organ System
## Causes in Alphabetical Order
- Alagille syndrome
- Amyloidosis
- Apolipoprotein C-II deficiency
- Apoprotein E deficiency
- Cholestanol storage disease
- Chronic pancreatitis
- Familial hypercholesterolaemia
- Familial hyperlipoproteinemia type 1
- Familial hyperlipoproteinemia type 3
- Familial hypertriglyceridaemia
- Glycogen storage disease type I
- Hypercholesterolemia
- Hyperchylomicronemia
- Hyperlipidaemia
- Hyperlipoproteinemia
- Hypertriglyceridemia
- Hypothyroidism
- Juvenile xanthogranuloma
- Familial hypercholesterolaemia
- Myxedema
- Nephrotic syndrome
- Obesity
- Primary biliary cirrhosis
- Sitosterolemia
- Type Ia hyperlipoproteinemia
- Type Ib hyperlipoproteinemia
- Type Ic hyperlipoproteinemia
- Type IIa hyperlipoproteinemia
- Type IIb hyperlipoproteinemia
- Type III hyperlipoproteinemia
- Type IV hyperlipoproteinemia
- Type V hyperlipoproteinemia
- Vitamin E deficiency
# Types
## Xanthelasma
A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Strictly, a xanthelasma is a distinct condition, only being called a xanthoma when becoming larger and nodular, assuming tumorous proportions. Still, it is often classified simply as a subtype of xanthoma.
## Xanthoma tuberosum
Xanthoma tuberosum is characterized by xanthomas located over the joints.
## Xanthoma tendinosum
Xanthoma tendinosum (also known as "Tendinous xanthoma") is clinically characterized by papules and nodules found in the tendons of the hands.
## Eruptive xanthoma
Eruptive xanthoma (ILDS E78.220) is clinically characterized by small, yellowish-orange to reddish-brown papules that appear all over the body.
## Xanthoma planum
Xanthoma planum (ILDS D76.370), also known as "Plane xanthoma", is clinically characterized by macules and plaques spread diffusely over large areas of the body.
## Palmar xanthoma
Palmar xanthoma is clinically characterized by yellowish plaques that involve the palms and flexural surfaces of the fingers. Plane xanthomas are characterised by yellowish to orange, flat macules or slightly elevated plaques, often with a central white area which may be localised or generalised. They often arise in the skin folds, especially the palmar creases. They occur in hyperlipoproteinaemia type III and type IIA, and in association with biliary cirrhosis. The presence of palmar xanthomata, like the presence of tendinous xanthomata, is indicative of hypercholesterolaemia.
## Tuberoeruptive xanthoma
Tuberoeruptive xanthoma (ILDS E78.210) is clinically characterized by red papules and nodules that appear inflamed and tend to coalesce. Tuberous xanthomas are considered similar, and within the same disease spectrum as tuberoeruptive xanthomas.
# Differential Diagnosis of Underlying Causes of Xanthoma
In alphabetical order.
- Juvenile xanthogranuloma
- Nodular basal cell carcinoma
- Sebaceous hyperplasia
- Syringoma | Xanthoma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]; Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [3]
Synonyms and keywords: Xanthoma, xanthomata, xanthomatosis
# Overview
A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis), from Greek xanthos, ξανθος, "yellow", is a deposition of yellowish cholesterol-rich material in tendons or other body parts in various disease states.[1] They are cutaneous manifestations of lipidosis in which there is an accumulation of lipids in large foam cells within the skin.[1]
They are associated with hyperlipidemias, both primary and secondary types.
Tendon Xanthoma are associated with Type II hyperlipidaemia and chronic biliary obstruction.
Palmar xanthomata and tuboeruptive xanthomata (over knees and elbows) occur in Type III hyperlipidaemia
# Causes
## Common causes of Xanthomas
- Hypercholesterolemia
- Hyperchylomicronemia
- Hyperlipidaemia
- Hyperlipoproteinemia
## Causes by Organ System
## Causes in Alphabetical Order
- Alagille syndrome
- Amyloidosis
- Apolipoprotein C-II deficiency
- Apoprotein E deficiency
- Cholestanol storage disease
- Chronic pancreatitis
- Familial hypercholesterolaemia
- Familial hyperlipoproteinemia type 1
- Familial hyperlipoproteinemia type 3
- Familial hypertriglyceridaemia
- Glycogen storage disease type I
- Hypercholesterolemia
- Hyperchylomicronemia
- Hyperlipidaemia
- Hyperlipoproteinemia
- Hypertriglyceridemia
- Hypothyroidism
- Juvenile xanthogranuloma
- Familial hypercholesterolaemia
- Myxedema
- Nephrotic syndrome
- Obesity
- Primary biliary cirrhosis
- Sitosterolemia
- Type Ia hyperlipoproteinemia
- Type Ib hyperlipoproteinemia
- Type Ic hyperlipoproteinemia
- Type IIa hyperlipoproteinemia
- Type IIb hyperlipoproteinemia
- Type III hyperlipoproteinemia
- Type IV hyperlipoproteinemia
- Type V hyperlipoproteinemia
- Vitamin E deficiency
# Types
## Xanthelasma
A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Strictly, a xanthelasma is a distinct condition, only being called a xanthoma when becoming larger and nodular, assuming tumorous proportions.[2] Still, it is often classified simply as a subtype of xanthoma.[3]
## Xanthoma tuberosum
Xanthoma tuberosum is characterized by xanthomas located over the joints.
## Xanthoma tendinosum
Xanthoma tendinosum (also known as "Tendinous xanthoma"[4]) is clinically characterized by papules and nodules found in the tendons of the hands.
## Eruptive xanthoma
Eruptive xanthoma (ILDS E78.220) is clinically characterized by small, yellowish-orange to reddish-brown papules that appear all over the body.
## Xanthoma planum
Xanthoma planum (ILDS D76.370), also known as "Plane xanthoma", is clinically characterized by macules and plaques spread diffusely over large areas of the body.
## Palmar xanthoma
Palmar xanthoma is clinically characterized by yellowish plaques that involve the palms and flexural surfaces of the fingers. Plane xanthomas are characterised by yellowish to orange, flat macules or slightly elevated plaques, often with a central white area which may be localised or generalised. They often arise in the skin folds, especially the palmar creases. They occur in hyperlipoproteinaemia type III and type IIA, and in association with biliary cirrhosis. The presence of palmar xanthomata, like the presence of tendinous xanthomata, is indicative of hypercholesterolaemia.
## Tuberoeruptive xanthoma
Tuberoeruptive xanthoma (ILDS E78.210) is clinically characterized by red papules and nodules that appear inflamed and tend to coalesce. Tuberous xanthomas are considered similar, and within the same disease spectrum as tuberoeruptive xanthomas.[4]
# Differential Diagnosis of Underlying Causes of Xanthoma
In alphabetical order. [5] [6]
- Juvenile xanthogranuloma
- Nodular basal cell carcinoma
- Sebaceous hyperplasia
- Syringoma | https://www.wikidoc.org/index.php/Ddx:Xanthomas | |
d72108b9a6631f4c9e89ea99d5b8bfba11164761 | wikidoc | Deadlift | Deadlift
The deadlift is a weight training exercise where one lifts a loaded barbell (or, in the case of the trapbar deadlift, a loaded trapbar) off the ground from a stabilized bent-over position. It is one of the three gauges of powerlifting, and is an excellent exercise for overall body development if done properly.
# Overview
The deadlift is a compound movement that works grip strength, and the primary muscles used in the deadlift are the erector spinae, the gluteus maximus, adductor magnus, hamstrings and the soleus.
The remaining muscles are involved in stability control. It is, in a sense, the purest single event test of strength because it is one of the few lifts of dead weight (weight lying on the ground). In most other lifts the weight changes direction or starts in the air and several other athletic skills such as balance, coordination are emphasized. For example, both Olympic weightlifting events require a great deal of athletic skill in addition to strength. In addition, it is commonly believed to be the oldest test of strength dating back to cultures who competed at lifting the heaviest stones.
# World records
The record under official powerlifting rules is 455 kg (1003 lb) by Andy Bolton.
The record for a strongman-style deadlift, with a longer bar and from a greater height, is held by Benedikt Magnusson, who deadlifted 500kg (1100 lb). This feat was a Tire Deadlift at the Arnold Classic in Columbus Ohio 2008. Sigmarsson deadlifted 523 kg from the knees in 1987.
# Muscles involved
- Torso
Front
Abdomen
Rectus abdominis (under aponeurosis)
Obliques
Abdominal external oblique muscle
Back
Iliocostalis
Intertransversarii laterales lumborum
Latissimus dorsi
Levator scapulae
Longissimus
Quadratus lumborum
Rhomboideus major
Serratus posterior superior
Serratus posterior inferior
Splenius cervicis
Teres Major
Trapezius muscle
- Front
Abdomen
Rectus abdominis (under aponeurosis)
Obliques
Abdominal external oblique muscle
- Abdomen
Rectus abdominis (under aponeurosis)
- Rectus abdominis (under aponeurosis)
- Obliques
Abdominal external oblique muscle
- Abdominal external oblique muscle
- Back
Iliocostalis
Intertransversarii laterales lumborum
Latissimus dorsi
Levator scapulae
Longissimus
Quadratus lumborum
Rhomboideus major
Serratus posterior superior
Serratus posterior inferior
Splenius cervicis
Teres Major
Trapezius muscle
- Iliocostalis
- Intertransversarii laterales lumborum
- Latissimus dorsi
- Levator scapulae
- Longissimus
- Quadratus lumborum
- Rhomboideus major
- Serratus posterior superior
- Serratus posterior inferior
- Splenius cervicis
- Teres Major
- Trapezius muscle
- Legs
Quadriceps
Rectus femoris
Vastus lateralis
Vastus intermedius
Vastus medialis
Hamstrings
Biceps femoris muscle, long head
Biceps femoris muscle, short head
Semitendinosus
Semimembranosus
- Quadriceps
Rectus femoris
Vastus lateralis
Vastus intermedius
Vastus medialis
- Rectus femoris
- Vastus lateralis
- Vastus intermedius
- Vastus medialis
- Hamstrings
Biceps femoris muscle, long head
Biceps femoris muscle, short head
Semitendinosus
Semimembranosus
- Biceps femoris muscle, long head
- Biceps femoris muscle, short head
- Semitendinosus
- Semimembranosus
- Hips
Gluteal muscles
Gluteus maximus
Gluteus minimus
Piriformis
Superior gemellus
- Gluteal muscles
Gluteus maximus
Gluteus minimus
- Gluteus maximus
- Gluteus minimus
- Piriformis
- Superior gemellus
- Forearms
Flexor digitorum profundus
- Flexor digitorum profundus
# Variations
The Romanian deadlift is commonly used by Olympic Weightlifters. This variation puts more emphasis on the hamstrings and glutes. To perform them, unlock the knees and let the weight descend until knee level by bending from the hips.
The Sumo deadlift is a variation of the deadlift whereby the legs are spread far apart to the sides (arms reaching down inside of legs), mimicking a sumo stance, hence the name. This variation changes the emphasis of the lift to the legs and glutes instead of the back. The sumo deadlift is purported to be easier for those with large waists as well as those with relatively long torsos and shorter arms. However, the sumo technique may place greater stress on the hips and hamstrings, as well as the connective tissues of the pelvic bone.
Deadlifts can be performed using dumbbells or barbells, with one hand or two hands & with one leg or two legs. Variations are only limited by the athlete's imagination. Other variations are the side deadlift or suitcase deadlift, deadlift from a box, rack pulls, deadlift lockouts, and "Kuck pulls"
The archaic "dead weight lift", or "dead weight lift with lifting bar" involved a T-bar with weight loaded on it while the lifter stood on sturdy chairs or other such platforms. A remarkably heavy amount of weight could be lifted in this manner due to its short range of motion; the main limitations are in the grip. This lift is similar to the modern day rack pulls, where a heavy amount of weight is lifted deadlift style a short distance in a power cage or squat rack.
Typically, there are two grips used: overhand, or pronated, and a mixed overhand-underhand (supinated) (sometimes called "offset," "staggered," "alternating", or "mixed") grip. Dependent on forearm strength, the overhand grip may result in the bar potentially rolling about. Some argue the mixed grip is capable of neutralizing this through the "physics of reverse torsion." The mixed grip also allows more weight to be used for this reason.
In order to prevent the bar from rolling out of the hands, some lifters have been known to use an Olympic lifting technique known as the "hook" grip. This is similar to an overhand grip, but the thumbs are inside, allowing the lifter to "hook" onto them with the fingers. The hook grip can make it easier to hold heavier weights using less grip strength, and keeps both shoulders and elbows in a symmetrical position. While it theoretically takes much of the stress off of the joints which might be created by the twisting of a mixed grip it has the disadvantage of being extremely uncomfortable for the thumbs, something which those who advocate it says will pass once a lifter becomes accustomed to it. Another, but rarely used method is a combination of the mixed overhand-underhand grip and the hook grip, preferred by people who lift heavier weights than their grip can handle, but who don't want to rely on lifting straps or other supportive gear.
You will find that many powerlifters adopt the overhand grip for their lower weight sets and move to the mixed grip to lift larger weights so they can achieve their one rep max.
The trapbar deadlift is a variation of the deadlift using a special U-shaped bar (a trapbar). This allows more clearance for the knees to pass "through" the bar. To perform the trapbar deadlift, one loads the bar, steps inside the hollow portion of the bar, bends down, grasps the handles, stands erect, then lowers the bar to the ground in the exact opposite path. Proponents of trapbar deadlifts include Hardgainer Magazine, Bob Whelan, the Cyberpump website, and Dr Ken Leistner and iron-game writer Paul Kelso.
Snatch-grip deadlift. Deadlifts from a platform.
# Dangers
Improper form can precipitate new conditions, aggravate existing ones, and possibly cause injury, especially the heavier the weight one lifts. Failure to keep the back straight during the movement causes undue stress to the spinal discs, by pinching the front and leaving a gap at the back, forcing the internal fluids to compress towards the back, and potentially causing a herniated disc. This is especially true of the lumbar region of the spine, which bears the bulk of the compressive forces on the upper body.
In addition, the compression can squeeze the spinal roots of the spinal cord, causing nerve-conditions like lumbago or sciatica.
It is important that those executing a deadlift be proficient in the recruitment (voluntary activation) of the deep abdominal and trunk muscles. In particular, it has been suggested that recruiting the Transverse Abdominus muscle provides a natural corset-like brace around the trunk, helping to protect against injury. A good method to help achieve this and avoid lower back injuries is to keep the abdominals braced using the Valsalva maneuver. This will build anterior support for the spine. However, as a cautionary note, this technique can drastically increase blood pressure during the exercise and should not be performed by people with known or suspected heart conditions.
Some weightlifters use special belts to keep their lower back stabilized. Whether or not these belts actually prevent injuries is debated but evidence shows using the belt moves the concentration of pressure within the abdomen towards the anterior, taking pressure off of the spine. Conversely, one school of thought suggests that the use of belts should be minimized, as it does not allow for the development of one's "stabilizer muscles", thereby increasing the potential of serious injury.
Using an underhand grip is potentially hazardous on heavy deadlifts as a supinated grip shortens the biceps muscle and increases the load on it, possibly leading to a rupture of the muscle or connecting tendons. The risk is most notable in individuals without full flexibility in the elbow joint. | Deadlift
The deadlift is a weight training exercise where one lifts a loaded barbell (or, in the case of the trapbar deadlift, a loaded trapbar) off the ground from a stabilized bent-over position. It is one of the three gauges of powerlifting, and is an excellent exercise for overall body development if done properly.
# Overview
The deadlift is a compound movement that works grip strength, and the primary muscles used in the deadlift are the erector spinae, the gluteus maximus, adductor magnus, hamstrings and the soleus.
The remaining muscles are involved in stability control. It is, in a sense, the purest single event test of strength because it is one of the few lifts of dead weight (weight lying on the ground). In most other lifts the weight changes direction or starts in the air and several other athletic skills such as balance, coordination are emphasized. For example, both Olympic weightlifting events require a great deal of athletic skill in addition to strength. In addition, it is commonly believed to be the oldest test of strength dating back to cultures who competed at lifting the heaviest stones.
# World records
The record under official powerlifting rules is 455 kg (1003 lb) by Andy Bolton.
[1]
The record for a strongman-style deadlift, with a longer bar and from a greater height, is held by Benedikt Magnusson, who deadlifted 500kg (1100 lb). This feat was a Tire Deadlift at the Arnold Classic in Columbus Ohio 2008. Sigmarsson deadlifted 523 kg from the knees in 1987.
# Muscles involved
- Torso
Front
Abdomen
Rectus abdominis (under aponeurosis)
Obliques
Abdominal external oblique muscle
Back
Iliocostalis
Intertransversarii laterales lumborum
Latissimus dorsi
Levator scapulae
Longissimus
Quadratus lumborum
Rhomboideus major
Serratus posterior superior
Serratus posterior inferior
Splenius cervicis
Teres Major
Trapezius muscle
- Front
Abdomen
Rectus abdominis (under aponeurosis)
Obliques
Abdominal external oblique muscle
- Abdomen
Rectus abdominis (under aponeurosis)
- Rectus abdominis (under aponeurosis)
- Obliques
Abdominal external oblique muscle
- Abdominal external oblique muscle
- Back
Iliocostalis
Intertransversarii laterales lumborum
Latissimus dorsi
Levator scapulae
Longissimus
Quadratus lumborum
Rhomboideus major
Serratus posterior superior
Serratus posterior inferior
Splenius cervicis
Teres Major
Trapezius muscle
- Iliocostalis
- Intertransversarii laterales lumborum
- Latissimus dorsi
- Levator scapulae
- Longissimus
- Quadratus lumborum
- Rhomboideus major
- Serratus posterior superior
- Serratus posterior inferior
- Splenius cervicis
- Teres Major
- Trapezius muscle
- Legs
Quadriceps
Rectus femoris
Vastus lateralis
Vastus intermedius
Vastus medialis
Hamstrings
Biceps femoris muscle, long head
Biceps femoris muscle, short head
Semitendinosus
Semimembranosus
- Quadriceps
Rectus femoris
Vastus lateralis
Vastus intermedius
Vastus medialis
- Rectus femoris
- Vastus lateralis
- Vastus intermedius
- Vastus medialis
- Hamstrings
Biceps femoris muscle, long head
Biceps femoris muscle, short head
Semitendinosus
Semimembranosus
- Biceps femoris muscle, long head
- Biceps femoris muscle, short head
- Semitendinosus
- Semimembranosus
- Hips
Gluteal muscles
Gluteus maximus
Gluteus minimus
Piriformis
Superior gemellus
- Gluteal muscles
Gluteus maximus
Gluteus minimus
- Gluteus maximus
- Gluteus minimus
- Piriformis
- Superior gemellus
- Forearms
Flexor digitorum profundus
- Flexor digitorum profundus
# Variations
The Romanian deadlift is commonly used by Olympic Weightlifters. This variation puts more emphasis on the hamstrings and glutes. To perform them, unlock the knees and let the weight descend until knee level by bending from the hips.
The Sumo deadlift is a variation of the deadlift whereby the legs are spread far apart to the sides (arms reaching down inside of legs), mimicking a sumo stance, hence the name. This variation changes the emphasis of the lift to the legs and glutes instead of the back. The sumo deadlift is purported to be easier for those with large waists as well as those with relatively long torsos and shorter arms. However, the sumo technique may place greater stress on the hips and hamstrings, as well as the connective tissues of the pelvic bone.
Deadlifts can be performed using dumbbells or barbells, with one hand or two hands & with one leg or two legs. Variations are only limited by the athlete's imagination. Other variations are the side deadlift or suitcase deadlift, deadlift from a box, rack pulls, deadlift lockouts, and "Kuck pulls"
The archaic "dead weight lift", or "dead weight lift with lifting bar" involved a T-bar with weight loaded on it while the lifter stood on sturdy chairs or other such platforms. A remarkably heavy amount of weight could be lifted in this manner due to its short range of motion; the main limitations are in the grip. This lift is similar to the modern day rack pulls, where a heavy amount of weight is lifted deadlift style a short distance in a power cage or squat rack.
Typically, there are two grips used: overhand, or pronated, and a mixed overhand-underhand (supinated) (sometimes called "offset," "staggered," "alternating", or "mixed") grip. Dependent on forearm strength, the overhand grip may result in the bar potentially rolling about. Some argue the mixed grip is capable of neutralizing this through the "physics of reverse torsion." The mixed grip also allows more weight to be used for this reason.
In order to prevent the bar from rolling out of the hands, some lifters have been known to use an Olympic lifting technique known as the "hook" grip. This is similar to an overhand grip, but the thumbs are inside, allowing the lifter to "hook" onto them with the fingers. The hook grip can make it easier to hold heavier weights using less grip strength, and keeps both shoulders and elbows in a symmetrical position. While it theoretically takes much of the stress off of the joints which might be created by the twisting of a mixed grip it has the disadvantage of being extremely uncomfortable for the thumbs, something which those who advocate it says will pass once a lifter becomes accustomed to it. Another, but rarely used method is a combination of the mixed overhand-underhand grip and the hook grip, preferred by people who lift heavier weights than their grip can handle, but who don't want to rely on lifting straps or other supportive gear.
You will find that many powerlifters adopt the overhand grip for their lower weight sets and move to the mixed grip to lift larger weights so they can achieve their one rep max.
The trapbar deadlift is a variation of the deadlift using a special U-shaped bar (a trapbar). This allows more clearance for the knees to pass "through" the bar. To perform the trapbar deadlift, one loads the bar, steps inside the hollow portion of the bar, bends down, grasps the handles, stands erect, then lowers the bar to the ground in the exact opposite path. Proponents of trapbar deadlifts include Hardgainer Magazine, Bob Whelan, the Cyberpump website, and Dr Ken Leistner and iron-game writer Paul Kelso.
Snatch-grip deadlift. Deadlifts from a platform.
# Dangers
Improper form can precipitate new conditions, aggravate existing ones, and possibly cause injury, especially the heavier the weight one lifts. Failure to keep the back straight during the movement causes undue stress to the spinal discs, by pinching the front and leaving a gap at the back, forcing the internal fluids to compress towards the back, and potentially causing a herniated disc. This is especially true of the lumbar region of the spine, which bears the bulk of the compressive forces on the upper body.
In addition, the compression can squeeze the spinal roots of the spinal cord, causing nerve-conditions like lumbago or sciatica.
It is important that those executing a deadlift be proficient in the recruitment (voluntary activation) of the deep abdominal and trunk muscles. In particular, it has been suggested that recruiting the Transverse Abdominus muscle provides a natural corset-like brace around the trunk, helping to protect against injury. A good method to help achieve this and avoid lower back injuries is to keep the abdominals braced using the Valsalva maneuver. This will build anterior support for the spine. However, as a cautionary note, this technique can drastically increase blood pressure during the exercise and should not be performed by people with known or suspected heart conditions.
Some weightlifters use special belts to keep their lower back stabilized. Whether or not these belts actually prevent injuries is debated but evidence shows using the belt moves the concentration of pressure within the abdomen towards the anterior, taking pressure off of the spine. Conversely, one school of thought suggests that the use of belts should be minimized, as it does not allow for the development of one's "stabilizer muscles", thereby increasing the potential of serious injury.
Using an underhand grip is potentially hazardous on heavy deadlifts as a supinated grip shortens the biceps muscle and increases the load on it, possibly leading to a rupture of the muscle or connecting tendons. The risk is most notable in individuals without full flexibility in the elbow joint. | https://www.wikidoc.org/index.php/Deadlift | |
1e5a01b5be598feaf7b351d610cb2b1a0f3dd258 | wikidoc | Dendrite | Dendrite
# Overview
Dendrites (from Greek dendron, “tree”) are the branched projections of a neuron that act to conduct the electrical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons via synapses which are located at various points throughout the dendritic arbor. Dendrites play a critical role in integrating these synaptic inputs and in determining the extent to which action potentials are produced by the neuron.
# Electrical properties of dendrites
The structure and branching of a neuron's dendrites, as well as the availability and variation in voltage-gated ion conductances, strongly influences how it integrates the input from other neurons, particularly those that input only weakly. This integration is both "temporal" -- involving the summation of stimuli that arrive in rapid succession -- as well as "spatial" -- entailing the aggregation of excitatory and inhibitory inputs from separate branches.
Dendrites were once believed to merely convey stimulation passively. In this example voltage changes measured at the cell body result from activations of distal synapses propagating to the soma without the aid of voltage-gated ion channels. Passive cable theory describes how voltage changes at a particular location on a dendrite transmit this electrical signal through a system of converging dendrite segments of different diameters, lengths, and electrical properties. Based on passive cable theory one can track how changes in a neuron’s dendritic morphology changes the membrane voltage at the soma, and thus how variation in dendrite architectures affects the overall output characteristics of the neuron.
Although passive cable theory offers insights regarding input propagation along dendrite segments, it is important to remember that dendrite membranes are host to a cornucopia of proteins some of which may help amplify or attenuate synaptic input. Sodium, calcium, and potassium channels are all implicated in contributing to input modulation. It is possible that each of these ion species has a family of channel types each with its own biophysical characteristics relevant to synaptic input modulation. Such characteristics include the latency of channel opening, the electrical conductance of the ion pore, the activation voltage, and the activation duration. In this way, a weak input from a distal synapse can be amplified by sodium and calcium currents en route to the soma so that the effects of distal synapse are no less robust than those of a proximal synapse.
One important feature of dendrites, endowed by their active voltage gated conductances, is their ability to send action potentials back into the dendritic arbor. Known as backpropagating action potentials, these signals depolarize the dendritic arbor and provide a crucial component toward synapse modulation and long-term potentiation. Furthermore, a train of backpropagating action potentials artificially generated at the soma can induce a calcium action potential at the dendritic initiation zone in certain types of neurons. Whether or not this mechanism is of physiological importance remains an open question.
# Dendrite development
File:Complete neuron cell diagram.svg
Despite the critical role that dendrites play in the computational tendencies of neurons, very little is known about the process by which dendrites orient themselves in vivo and are compelled to create the intricate branching pattern unique to each specific neuronal class. It is likely that a complex array of extracellular and intracellular cues modulate dendrite development. Early candidates include: Sema3A, Notch, CREST, and Dasm1. Sema3A may act as a dendritic chemoattractant that aids cortical pyramidal neurons in orienting their apical dendrites to the pial surface. Notch acts as a neurotrophic factor in aiding dendrite growth and branching, while CREST may play an important role in regulating calcium dependent growth signals. Dasm1 (Dendrite arborization and synapse maturation 1) expression appears to be highly localized to dendrites and may have substantial influence on dendrite (but not axon) development. | Dendrite
Template:Neuron map
Template:Portalpar
# Overview
Dendrites (from Greek dendron, “tree”) are the branched projections of a neuron that act to conduct the electrical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons via synapses which are located at various points throughout the dendritic arbor. Dendrites play a critical role in integrating these synaptic inputs and in determining the extent to which action potentials are produced by the neuron.
# Electrical properties of dendrites
The structure and branching of a neuron's dendrites, as well as the availability and variation in voltage-gated ion conductances, strongly influences how it integrates the input from other neurons, particularly those that input only weakly. This integration is both "temporal" -- involving the summation of stimuli that arrive in rapid succession -- as well as "spatial" -- entailing the aggregation of excitatory and inhibitory inputs from separate branches.
Dendrites were once believed to merely convey stimulation passively. In this example voltage changes measured at the cell body result from activations of distal synapses propagating to the soma without the aid of voltage-gated ion channels. Passive cable theory describes how voltage changes at a particular location on a dendrite transmit this electrical signal through a system of converging dendrite segments of different diameters, lengths, and electrical properties. Based on passive cable theory one can track how changes in a neuron’s dendritic morphology changes the membrane voltage at the soma, and thus how variation in dendrite architectures affects the overall output characteristics of the neuron.
Although passive cable theory offers insights regarding input propagation along dendrite segments, it is important to remember that dendrite membranes are host to a cornucopia of proteins some of which may help amplify or attenuate synaptic input. Sodium, calcium, and potassium channels are all implicated in contributing to input modulation. It is possible that each of these ion species has a family of channel types each with its own biophysical characteristics relevant to synaptic input modulation. Such characteristics include the latency of channel opening, the electrical conductance of the ion pore, the activation voltage, and the activation duration. In this way, a weak input from a distal synapse can be amplified by sodium and calcium currents en route to the soma so that the effects of distal synapse are no less robust than those of a proximal synapse.
One important feature of dendrites, endowed by their active voltage gated conductances, is their ability to send action potentials back into the dendritic arbor. Known as backpropagating action potentials, these signals depolarize the dendritic arbor and provide a crucial component toward synapse modulation and long-term potentiation. Furthermore, a train of backpropagating action potentials artificially generated at the soma can induce a calcium action potential at the dendritic initiation zone in certain types of neurons. Whether or not this mechanism is of physiological importance remains an open question.
# Dendrite development
File:Complete neuron cell diagram.svg
Despite the critical role that dendrites play in the computational tendencies of neurons, very little is known about the process by which dendrites orient themselves in vivo and are compelled to create the intricate branching pattern unique to each specific neuronal class. It is likely that a complex array of extracellular and intracellular cues modulate dendrite development. Early candidates include: Sema3A, Notch, CREST, and Dasm1. Sema3A may act as a dendritic chemoattractant that aids cortical pyramidal neurons in orienting their apical dendrites to the pial surface. Notch acts as a neurotrophic factor in aiding dendrite growth and branching, while CREST may play an important role in regulating calcium dependent growth signals. Dasm1 (Dendrite arborization and synapse maturation 1) expression appears to be highly localized to dendrites and may have substantial influence on dendrite (but not axon) development. | https://www.wikidoc.org/index.php/Dendrite | |
e103719abd6fc9953a33b14fefe51238dc886c59 | wikidoc | Mandible | Mandible
The mandible (from Latin mandibūla, "jawbone") or inferior maxillary bone is, together with the maxilla, the largest and strongest bone of the face. It forms the lower jaw and holds the lower teeth in place.
# Components
The mandible consists of:
- a curved, horizontal portion, the body. (See body of mandible).
- two perpendicular portions, the rami, which unite with the ends of the body nearly at right angles. (See ramus mandibulae)
- Alveolar process, the tooth bearing area of the mandible (upper part of the body of the mandible)
- Condyle, superior (upper) and posterior projection from the ramus, which makes the temporomandibular joint with the temporal bone
- Coronoid process, superior and anterior projection from the ramus. This provides attachment to the temporalis muscle
# Foramens
- Mandibular foramen, paired, in the inner (medial) aspect of the mandible, superior to the mandibular angle in the middle of the ramus.
- Mental foramen, paired, lateral to the mental protuberance on the body of mandible.
# Nerves
Inferior alveolar nerve, branch of the mandibular division of Trigeminal (V) nerve, enters the mandibular foramen and runs forward in the mandibular canal, supplying sensation to the teeth. At the mental foramen the nerve divides into two terminal branches: incisive and mental nerves. The incisive nerve runs forward in the mandible and supplies the anterior teeth. The mental nerve exits the mental foramen and supplies sensation to the lower lip.
# Articulations
The mandible articulates with the two temporal bones at the temporomandibular joints.
# Injuries
Mandibular fractures are often accompanied by a 'twin fracture' on the contralateral (opposite) side.
The mandible may be dislocated anteriorly (to the front) and inferiorly (downwards) but very rarely posteriorly (backwards). | Mandible
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:Infobox Bone
The mandible (from Latin mandibūla, "jawbone") or inferior maxillary bone is, together with the maxilla, the largest and strongest bone of the face. It forms the lower jaw and holds the lower teeth in place.
# Components
The mandible consists of:
- a curved, horizontal portion, the body. (See body of mandible).
- two perpendicular portions, the rami, which unite with the ends of the body nearly at right angles. (See ramus mandibulae)
- Alveolar process, the tooth bearing area of the mandible (upper part of the body of the mandible)
- Condyle, superior (upper) and posterior projection from the ramus, which makes the temporomandibular joint with the temporal bone
- Coronoid process, superior and anterior projection from the ramus. This provides attachment to the temporalis muscle
# Foramens
- Mandibular foramen, paired, in the inner (medial) aspect of the mandible, superior to the mandibular angle in the middle of the ramus.
- Mental foramen, paired, lateral to the mental protuberance on the body of mandible.
# Nerves
Inferior alveolar nerve, branch of the mandibular division of Trigeminal (V) nerve, enters the mandibular foramen and runs forward in the mandibular canal, supplying sensation to the teeth. At the mental foramen the nerve divides into two terminal branches: incisive and mental nerves. The incisive nerve runs forward in the mandible and supplies the anterior teeth. The mental nerve exits the mental foramen and supplies sensation to the lower lip.
# Articulations
The mandible articulates with the two temporal bones at the temporomandibular joints.
# Injuries
Mandibular fractures are often accompanied by a 'twin fracture' on the contralateral (opposite) side.
The mandible may be dislocated anteriorly (to the front) and inferiorly (downwards) but very rarely posteriorly (backwards). | https://www.wikidoc.org/index.php/Dentary | |
5f7dbb018e2f4357bdf3491cd43842b15b6f7075 | wikidoc | Dentures | Dentures
# Overview
Dentures are prosthetic devices constructed to replace missing teeth, and which are supported by surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable, however there are many different denture designs, some which rely on bonding or clipping onto teeth or dental implants. There are two main categories of dentures, depending on whether they are used to replace missing teeth on the mandibular arch or the maxillary arch. There are many informal names for dentures such as dental plate, false teeth and falsies.
# Causes of tooth loss
Patients can become entirely edentulous (without teeth) due to many reasons, the most prevalent being removal because of dental disease typically relating to oral flora control ie:periodontal disease and tooth decay. Other reasons include tooth developmental defects caused by severe malnutrition, genetic defects such as Dentinogenesis imperfecta, trauma, or drug use.
# Advantages
Dentures can help patients in terms of:
1. Masticatory - improving chewing ability by replacing the edentulous area with acrylic teeth. Thus enable better mastication and pleasure to enjoy food.
2. Aesthetic - providing the illusion of having natural teeth, providing support for their lips and cheeks, and correcting the collapsed appearance commonly seen between the nose and the chin.
3. Phonetic - Replacing the toothless area, especially the anteriors, to help patients to speak and pronounce certain words properly without air escapes.
# Types of dentures
## Removable partial dentures
Removable partial dentures are for patients who are missing some of their teeth on a particular arch. Fixed partial dentures, better known as "crown and bridge", are made from crowns that are fitted on the remaining teeth to act as abutments and pontics made from materials to resemble the missing teeth. Fixed bridges are more expensive than removable appliances but are more stable.
## Complete dentures
Conversely, complete dentures or full dentures are worn by patients who are missing all their teeth in an arch (i.e the maxillary(upper) or mandibular(lower) arch).
# History
Around 700BC, Etruscans, in northern Italy, made dentures out of human or other animal teeth. These deteriorated quickly but, being easy to produce, were popular until mid 19th century
The first European sets of dentures date from the 15th century and most probably existed before that time. They were carved from bone or ivory, or made up of teeth sourced from graveyards, the recent dead or living donors who exchanged their teeth for profit. These dentures were uncomfortable, attached visibly to a base supported by any remaining teeth with a thread of metal or silk. The false teeth were often made with ivory from the hippopotamus or walrus, and usually rotted after extended use.
London's Peter de la Roche is believed to be one of the first 'Operators for the Teeth', men who fashioned themselves as specialists in dental work. Often these men were professional goldsmiths, ivory turners or students of barber-surgeons.
The first porcelain dentures were made around 1770 by Alexis Duchâteau. In 1791 the first British patent was granted to Nicholas Dubois De Chemant, previously assistant to Duchateau, for De Chemant's Specification, "a composition for the purpose of making of artificial teeth either single double or in rows or in complete sets and also springs for fastening or affixing the same in a more easy and effectual manner than any hitherto discovered which said teeth may be made of any shade or colour, which they will retain for any length of time and will consequently more perfectly resemble the natural teeth." He began selling his wares in 1792 with most of his porcelain paste supplied by Wedgwood. Single teeth in porcelain were made since 1808. Later dentures were made of vulcanite and then, in the 20th century, acrylic resin and other plastics. In Britain in 1968 79% of those aged 65-74 had no natural teeth, by 1998 this proportion had fallen to 36%.
# Problems with complete dentures
Problems with dentures include the fact that patients are not used to having something in their mouth that is not food. The brain senses this appliance as "food" and sends messages to the salivary glands to produce more saliva and to secrete it at a higher rate. New dentures will also be the inevitable cause of sore spots as they rub and press on the mucosa (denture bearing soft tissue). A few denture adjustments for the weeks following insertion of the dentures can take care of this issue. Gagging is another problem encountered by some patients. At times, this may be due to a denture that is too loose fitting, too thick or extended too far posteriorly onto the soft palate. At times, gagging may also be attributed to psychological denial of the denture. (Psychological gagging is the most difficult to treat since it is out of the dentist's control. In such cases, an implant supported palateless denture may have to be constructed or a hypnotist may need to be consulted). Sometimes there could be a gingivitis under the full dentures, which is caused by accumulation of dental plaque.
Another problem with dentures is keeping them in place. There are three rules governing the existence of removable oral appliances: support, stability and retention.
# Prosthodontic principles of dentures
## Support
Support is the principle that describes how well the underlying mucosa (oral tissues, including gums and the vestibules} keeps the denture from moving in the vertical plane towards the arch in question, and thus being excessively depressed and moving deeper into the arch. For the mandibular arch, this function is provided by the gingiva (gums) and the buccal shelf (region extending laterally (beside) from the posterior (back) ridges), whereas in the maxillary arch, the palate joins in to help support the denture. The larger the denture flanges (part of the denture that extends into the vestibule), the better the support.
More recently, there has been a move to increase denture stability with implants. When pressure is applied to alveolar bone bereft of teeth (alveolar bone is the bone in which teeth normally reside), the bone reacts to this pressure by resorbing. After many years of denture wearing, the ridges upon which the dentures rest deteriorate and can easily all but disappear. The insertion of implants into the bone below the dentures can help to seriously combat this unfortunate occurrence. The implants are strategically placed to bear the brunt of the pressure when the denture is used for chewing, keeping the bone from melting away. When implants are integrated into treatment, the denture is now referred to as being an implant supported overdenture and the implants are referred to as overdenture abutments.
## Stability
Stability is the principle that describes how well the denture base is prevented from moving in the horizontal plane, and thus from sliding side to side or front and back. The more the denture base (pink material) runs in smooth and continuous contact with the edentulous ridge (the hill upon which the teeth used to reside, but now consists of only residual alveolar bone with overlying mucosa), the better the stability. Of course, the higher and broader the ridge, the better the stability will be, but this is usually just a result of patient anatomy, barring surgical intervention (bone grafts, etc.).
## Retention
Retention is the principle that describes how well the denture is prevented from moving in the vertical plane in the opposite direction of insertion. The better the topographical mimicry of the intaglio (interior) surface of the denture base to the surface of the underlying mucosa, the better the retention will be (in removable partial dentures, the clasps are a major provider of retention), as surface tension, suction and just plain old friction will aid in keeping the denture base from breaking intimate contact with the mucosal surface. It is important to note that the most critical element in the retentive design of a full maxillary denture is a complete and total border seal (complete peripheral seal) in order to achieve 'suction'. The border seal is composed of the edges of the anterior and lateral aspects AND the posterior palatal seal. The posterior palatal seal design is accomplished by covering the entire hard palate and extending not beyond the soft palate and ending 1-2mm from the vibrating line.
As mentioned above, implant technology can vastly improve the patient's denture-wearing experience by increasing stability and saving his or her bone from wearing away. Implant can also help with the retention factor. Instead of merely placing the implants to serve as blocking mechanism against the denture pushing on the alveolar bone, small retentive appliances can be attached to the implants that can then snap into a modified denture base to allow for tremendously increased retention. Options available include a metal Hader bar or precision balls attachments, among other things.
## Complications and recommendations
The fabrication of a set of complete dentures is a challenge for any dentist, including those who are experienced. There are many axioms in the production of dentures that must be understood, of which ignorance of one axiom can lead to failure of the denture case. In the vast majority of cases, complete dentures should be comfortable soon after insertion, although almost always at least two adjustment visits will be necessary to remove sore spots. One of the most critical aspects of dentures is that the impression of the denture must be perfectly made and used with perfect technique to make a model of the patient's edentulous (toothless) gums. The dentist must use a process called border molding to ensure that the denture flanges are properly extended. An endless array of never-ending problems with denture may occur if the final impression of the denture is not made properly. It takes considerable patience and experience for a dentist to know how to make a denture, and for this reason it may be in the patient's best interest to seek a specialist, either a Denturist or a Prosthodontist, to make the denture. A general dentist may do a good job, but only if he or she is meticulous and usually he or she must be experienced.
The maxillary denture (the top denture) is usually relatively straightforward to manufacture so that it is stable without slippage. The lower full denture tends to be the most difficult because there is no "suction" holding it in place. For this reason, dentists in the late 1990s have come to a general conclusion that a lower full denture should or must be supported by 2-4 implants placed in the lower jaw for support. A lower denture supported by 2-4 implants is a far superior product than a lower denture without implants, held in place with weak lower mouth muscles. It is routine to be able to bite into an apple or corn-on-the-cob with a lower denture anchored by implants. Without implants, it is quite difficult or even impossible to do so.
Some patients who believe they have "bad teeth" may think it is in their best interests to have all their teeth extracted and full dentures placed. However, statistics show that the majority of patients who actually receive this treatment wind up regretting they did so. This is because full dentures have only 10% of the chewing power of natural teeth, and it is difficult to get them fitted satisfactorily, particularly in the mandibular arch. Even if a patient retains one tooth, that will contribute to the denture's stability. However, retention of just one or two teeth in the upper jaw does not contribute much to the overall stability of a denture, since a full upper denture tends to be very stable, in contrast to a full lower denture. It is thus advised that patients keep their natural teeth as long as possible, especially their lower teeth.
# Conclusion
As can be expected with any removable appliance placed in the mouth, there will be some problems (in respect to the three principles mentioned above) with dentures no matter how well they are made. This is because the best the dentist can do is fabricate the upper denture to work in harmony with the lower denture when the patient is at rest. If the only variables in the equation are the patient's edentulous ridges and the two dentures, the dentist can set the teeth in certain ways to help prevent dislodgement during opening, closing and swallowing. Once food enters into the picture, though, the stability of the denture bases is not impervious to disruption. During chewing, the denture bases will sometimes act as class 1 levers, and when the patient bites down on the anterior, or front, teeth, the posterior, or rear, teeth are bound to move away from the ridge. Although the ideals of denture design will have it that the intaglio surface is in perfect, intimate contact with the ridge and the margins of the denture base will create a perfect suction seal (the seal is actually only on the maxillary denture), ideals are rarely if ever met in this imperfect world, and thus some movement is to be expected. Denture adhesive can then be utilized to compete against the forces trying to pull the denture base away from the mucosa. In a perfect world, a patient with a perfect edentulous ridge with a perfectly fitting denture would require no adhesive, as the actual form of the denture base should work in tandem with the three principles mentioned above, thus precluding movement in any way, shape or form. | Dentures
# Overview
Dentures are prosthetic devices constructed to replace missing teeth, and which are supported by surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable, however there are many different denture designs, some which rely on bonding or clipping onto teeth or dental implants. There are two main categories of dentures, depending on whether they are used to replace missing teeth on the mandibular arch or the maxillary arch. There are many informal names for dentures such as dental plate, false teeth and falsies.
# Causes of tooth loss
Patients can become entirely edentulous (without teeth) due to many reasons, the most prevalent being removal because of dental disease typically relating to oral flora control ie:periodontal disease and tooth decay. Other reasons include tooth developmental defects caused by severe malnutrition, genetic defects such as Dentinogenesis imperfecta, trauma, or drug use.
# Advantages
Dentures can help patients in terms of:
1. Masticatory - improving chewing ability by replacing the edentulous area with acrylic teeth. Thus enable better mastication and pleasure to enjoy food.
2. Aesthetic - providing the illusion of having natural teeth, providing support for their lips and cheeks, and correcting the collapsed appearance commonly seen between the nose and the chin.
3. Phonetic - Replacing the toothless area, especially the anteriors, to help patients to speak and pronounce certain words properly without air escapes.
# Types of dentures
## Removable partial dentures
Removable partial dentures are for patients who are missing some of their teeth on a particular arch. Fixed partial dentures, better known as "crown and bridge", are made from crowns that are fitted on the remaining teeth to act as abutments and pontics made from materials to resemble the missing teeth. Fixed bridges are more expensive than removable appliances but are more stable.
## Complete dentures
Conversely, complete dentures or full dentures are worn by patients who are missing all their teeth in an arch (i.e the maxillary(upper) or mandibular(lower) arch).
# History
Around 700BC, Etruscans, in northern Italy, made dentures out of human or other animal teeth. These deteriorated quickly but, being easy to produce, were popular until mid 19th century[1]
The first European sets of dentures date from the 15th century and most probably existed before that time. They were carved from bone or ivory, or made up of teeth sourced from graveyards, the recent dead or living donors who exchanged their teeth for profit. These dentures were uncomfortable, attached visibly to a base supported by any remaining teeth with a thread of metal or silk. The false teeth were often made with ivory from the hippopotamus or walrus, and usually rotted after extended use.[citation needed]
London's Peter de la Roche is believed to be one of the first 'Operators for the Teeth', men who fashioned themselves as specialists in dental work. Often these men were professional goldsmiths, ivory turners or students of barber-surgeons.[2]
The first porcelain dentures were made around 1770 by Alexis Duchâteau. In 1791 the first British patent was granted to Nicholas Dubois De Chemant, previously assistant to Duchateau, for De Chemant's Specification, "a composition for the purpose of making of artificial teeth either single double or in rows or in complete sets and also springs for fastening or affixing the same in a more easy and effectual manner than any hitherto discovered which said teeth may be made of any shade or colour, which they will retain for any length of time and will consequently more perfectly resemble the natural teeth." He began selling his wares in 1792 with most of his porcelain paste supplied by Wedgwood.[citation needed] Single teeth in porcelain were made since 1808. Later dentures were made of vulcanite and then, in the 20th century, acrylic resin and other plastics. In Britain in 1968 79% of those aged 65-74 had no natural teeth, by 1998 this proportion had fallen to 36%.[citation needed]
# Problems with complete dentures
Problems with dentures include the fact that patients are not used to having something in their mouth that is not food. The brain senses this appliance as "food" and sends messages to the salivary glands to produce more saliva and to secrete it at a higher rate. New dentures will also be the inevitable cause of sore spots as they rub and press on the mucosa (denture bearing soft tissue). A few denture adjustments for the weeks following insertion of the dentures can take care of this issue. Gagging is another problem encountered by some patients. At times, this may be due to a denture that is too loose fitting, too thick or extended too far posteriorly onto the soft palate. At times, gagging may also be attributed to psychological denial of the denture. (Psychological gagging is the most difficult to treat since it is out of the dentist's control. In such cases, an implant supported palateless denture may have to be constructed or a hypnotist may need to be consulted). Sometimes there could be a gingivitis under the full dentures, which is caused by accumulation of dental plaque.
Another problem with dentures is keeping them in place. There are three rules governing the existence of removable oral appliances: support, stability and retention.
# Prosthodontic principles of dentures
## Support
Support is the principle that describes how well the underlying mucosa (oral tissues, including gums and the vestibules} keeps the denture from moving in the vertical plane towards the arch in question, and thus being excessively depressed and moving deeper into the arch. For the mandibular arch, this function is provided by the gingiva (gums) and the buccal shelf (region extending laterally (beside) from the posterior (back) ridges), whereas in the maxillary arch, the palate joins in to help support the denture. The larger the denture flanges (part of the denture that extends into the vestibule), the better the support.
More recently, there has been a move to increase denture stability with implants. When pressure is applied to alveolar bone bereft of teeth (alveolar bone is the bone in which teeth normally reside), the bone reacts to this pressure by resorbing. After many years of denture wearing, the ridges upon which the dentures rest deteriorate and can easily all but disappear. The insertion of implants into the bone below the dentures can help to seriously combat this unfortunate occurrence. The implants are strategically placed to bear the brunt of the pressure when the denture is used for chewing, keeping the bone from melting away. When implants are integrated into treatment, the denture is now referred to as being an implant supported overdenture and the implants are referred to as overdenture abutments.
## Stability
Stability is the principle that describes how well the denture base is prevented from moving in the horizontal plane, and thus from sliding side to side or front and back. The more the denture base (pink material) runs in smooth and continuous contact with the edentulous ridge (the hill upon which the teeth used to reside, but now consists of only residual alveolar bone with overlying mucosa), the better the stability. Of course, the higher and broader the ridge, the better the stability will be, but this is usually just a result of patient anatomy, barring surgical intervention (bone grafts, etc.).
## Retention
Retention is the principle that describes how well the denture is prevented from moving in the vertical plane in the opposite direction of insertion. The better the topographical mimicry of the intaglio (interior) surface of the denture base to the surface of the underlying mucosa, the better the retention will be (in removable partial dentures, the clasps are a major provider of retention), as surface tension, suction and just plain old friction will aid in keeping the denture base from breaking intimate contact with the mucosal surface. It is important to note that the most critical element in the retentive design of a full maxillary denture is a complete and total border seal (complete peripheral seal) in order to achieve 'suction'. The border seal is composed of the edges of the anterior and lateral aspects AND the posterior palatal seal. The posterior palatal seal design is accomplished by covering the entire hard palate and extending not beyond the soft palate and ending 1-2mm from the vibrating line.
As mentioned above, implant technology can vastly improve the patient's denture-wearing experience by increasing stability and saving his or her bone from wearing away. Implant can also help with the retention factor. Instead of merely placing the implants to serve as blocking mechanism against the denture pushing on the alveolar bone, small retentive appliances can be attached to the implants that can then snap into a modified denture base to allow for tremendously increased retention. Options available include a metal Hader bar or precision balls attachments, among other things.
## Complications and recommendations
The fabrication of a set of complete dentures is a challenge for any dentist, including those who are experienced. There are many axioms in the production of dentures that must be understood, of which ignorance of one axiom can lead to failure of the denture case. In the vast majority of cases, complete dentures should be comfortable soon after insertion, although almost always at least two adjustment visits will be necessary to remove sore spots. One of the most critical aspects of dentures is that the impression of the denture must be perfectly made and used with perfect technique to make a model of the patient's edentulous (toothless) gums. The dentist must use a process called border molding to ensure that the denture flanges are properly extended. An endless array of never-ending problems with denture may occur if the final impression of the denture is not made properly. It takes considerable patience and experience for a dentist to know how to make a denture, and for this reason it may be in the patient's best interest to seek a specialist, either a Denturist or a Prosthodontist, to make the denture. A general dentist may do a good job, but only if he or she is meticulous and usually he or she must be experienced.
The maxillary denture (the top denture) is usually relatively straightforward to manufacture so that it is stable without slippage. The lower full denture tends to be the most difficult because there is no "suction" holding it in place. For this reason, dentists in the late 1990s have come to a general conclusion that a lower full denture should or must be supported by 2-4 implants placed in the lower jaw for support. A lower denture supported by 2-4 implants is a far superior product than a lower denture without implants, held in place with weak lower mouth muscles. It is routine to be able to bite into an apple or corn-on-the-cob with a lower denture anchored by implants. Without implants, it is quite difficult or even impossible to do so.
Some patients who believe they have "bad teeth" may think it is in their best interests to have all their teeth extracted and full dentures placed. However, statistics show that the majority of patients who actually receive this treatment wind up regretting they did so. This is because full dentures have only 10% of the chewing power of natural teeth, and it is difficult to get them fitted satisfactorily, particularly in the mandibular arch. Even if a patient retains one tooth, that will contribute to the denture's stability. However, retention of just one or two teeth in the upper jaw does not contribute much to the overall stability of a denture, since a full upper denture tends to be very stable, in contrast to a full lower denture. It is thus advised that patients keep their natural teeth as long as possible, especially their lower teeth.
# Conclusion
As can be expected with any removable appliance placed in the mouth, there will be some problems (in respect to the three principles mentioned above) with dentures no matter how well they are made. This is because the best the dentist can do is fabricate the upper denture to work in harmony with the lower denture when the patient is at rest. If the only variables in the equation are the patient's edentulous ridges and the two dentures, the dentist can set the teeth in certain ways to help prevent dislodgement during opening, closing and swallowing. Once food enters into the picture, though, the stability of the denture bases is not impervious to disruption. During chewing, the denture bases will sometimes act as class 1 levers, and when the patient bites down on the anterior, or front, teeth, the posterior, or rear, teeth are bound to move away from the ridge. Although the ideals of denture design will have it that the intaglio surface is in perfect, intimate contact with the ridge and the margins of the denture base will create a perfect suction seal (the seal is actually only on the maxillary denture), ideals are rarely if ever met in this imperfect world, and thus some movement is to be expected. Denture adhesive can then be utilized to compete against the forces trying to pull the denture base away from the mucosa. In a perfect world, a patient with a perfect edentulous ridge with a perfectly fitting denture would require no adhesive, as the actual form of the denture base should work in tandem with the three principles mentioned above, thus precluding movement in any way, shape or form. | https://www.wikidoc.org/index.php/Denture | |
e504a515a2b22f6284d2efa6cc472989cd731f2a | wikidoc | Derbisol | Derbisol
Derbisol is a fictitious drug used in questionnaires by some academic surveys to test the reliability of answers received by students.
Some such questionnaires ( etc) give Derbisol the slang names "DB" and "derbs" and "dirt".
Another common fictitious drug used in questionnaires is "shimeron."
This drug information web site (in Korean) seems to use "Derbisol®" as a trade name for Clobetasol. | Derbisol
Derbisol is a fictitious drug used in questionnaires by some academic surveys to test the reliability of answers received by students.
Some such questionnaires ([1] etc) give Derbisol the slang names "DB" and "derbs" and "dirt".
Another common fictitious drug used in questionnaires is "shimeron." [2]
This drug information web site (in Korean) seems to use "Derbisol®" as a trade name for Clobetasol.
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Derbisol | |
d3f0a086b2321f38a46317212860ea413c29ecf6 | wikidoc | Derlin-1 | Derlin-1
Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a membrane protein that in humans is encoded by the DERL1 gene. Derlin-1 is located in the membrane of the endoplasmic reticulum (ER) and is involved in retrotranslocation of specific misfolded proteins and in ER stress. Derlin-1 is widely expressed in thyroid, fat, bone marrow and many other tissues. The protein belongs to the Derlin-family proteins (also called derlins) consisting of derlin-1, derlin-2 and derlin-3 that are components in the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The derlins mediate degradation of misfolded lumenal proteins within ER, and are named ‘der’ for their ‘Degradation in the ER’. Derlin-1 is a mammalian homologue of the yeast DER1 protein, a protein involved in the yeast ERAD pathway. Moreover, derlin-1 is a member of the rhomboid-like clan of polytopic membrane proteins.
Overexpression of derlin-1 are associated with many cancers, including colon cancer, breast cancer, bladder cancer and non-small cell lung cancer.
# Discovery
In 2004 the DERL1 gene was discovered independently by two research groups when they were exploring the machinery of retrotranslocation in the ER in the cell. One evidence for the existence of DERL1 was provided by Professor Tom A. Rapoport and his research group at Horward Medical School, Boston, Massachusetts. Another evidence of the DERL1 gene was discovered by Professor Hidde L. Ploegh and his research group who is also at Horward Medical School, Boston, Massachusetts. As the mammalian DERL1 gene was found to be a homologue of the yeast DER1 gene found in 1996, it was named after the yeast gene.
# Gene location
The human DERL1 gene is located on the long (q) arm of chromosome 8 at region 2 band 4, from base pair 123,013,164 to 123,042,423 (Build GRCh37/hg19) (map).
# Function and mechanism
## Rerouting factor during ER stress
ER stress is caused by an accumulation of unfolded or misfolded proteins in ER and is critical for cell function. The accumulation of unfolded and misfolded proteins activates an unfolded protein response (UPR) which regulate the homeostasis of the cell. One of the strategies cells possess to ER stress as a quality control system is the ERAD pathway, by which Derlin-1 is a component of. As a part of an ER membrane protein complex (that includes VIMP, SEL1, HRD1, and HERP) derlin-1 detects misfolded proteins in ER and mediate them for their degradation in the ERAD pathway.
Under ER stress, the carboxyl-terminus region of derlin-1 captures specific misfolded proteins in the ER lumen. Derlin-1 also interacts with VIMP, an ER membrane protein that recruits the cytosolic ATPase p97 and its cofactor. The interaction of derlin-1 with p97 via VIMP is essential for export of misfolded proteins. p97 is required for the transport of the misfolded proteins through the ER membrane and back to the cytosolic side for their degradation. This process is referred to as retrotranslocation. Hence, one of the functions of derlin-1 is to reroute specific misfolded protein to the cytosol for their degradation. Prior to the cytosolic degradation, the retrotranslocated misfolded proteins interacts with HRDI E3 ubiquitin ligase. This ligase ubiquitinates the misfolded proteins promoting their degradation in the cytosol by the ubiquitin-protease system (UPS). Currently, the molecular mechanism by which derlin-1 reroutes the misfolded proteins from ER to their degradation are not fully understood.
# Clinical significance
Derlin 1 (DERL1) is up-regulated in metastatic canine mammary tumors as part of the unfolded protein response.
# Interactions
Derlin-1 has been shown to interact with the following proteins:
- HRD1
- VIMP
- US11 | Derlin-1
Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a membrane protein that in humans is encoded by the DERL1 gene.[1][2][3][4] Derlin-1 is located in the membrane of the endoplasmic reticulum (ER) and is involved in retrotranslocation of specific misfolded proteins and in ER stress.[2][4] Derlin-1 is widely expressed in thyroid, fat, bone marrow and many other tissues.[5] The protein belongs to the Derlin-family proteins (also called derlins) consisting of derlin-1, derlin-2 and derlin-3 that are components in the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The derlins mediate degradation of misfolded lumenal proteins within ER,[2][4][6][7] and are named ‘der’ for their ‘Degradation in the ER’.[8] Derlin-1 is a mammalian homologue of the yeast DER1 protein, a protein involved in the yeast ERAD pathway.[2][4][8] Moreover, derlin-1 is a member of the rhomboid-like clan of polytopic membrane proteins.[6]
Overexpression of derlin-1 are associated with many cancers, including colon cancer, breast cancer, bladder cancer and non-small cell lung cancer.[9][10][11][12][13]
# Discovery
In 2004 the DERL1 gene was discovered independently by two research groups when they were exploring the machinery of retrotranslocation in the ER in the cell.[2][4] One evidence for the existence of DERL1 was provided by Professor Tom A. Rapoport and his research group at Horward Medical School, Boston, Massachusetts.[4] Another evidence of the DERL1 gene was discovered by Professor Hidde L. Ploegh and his research group who is also at Horward Medical School, Boston, Massachusetts.[2] As the mammalian DERL1 gene was found to be a homologue of the yeast DER1 gene found in 1996,[8] it was named after the yeast gene.[2][4]
# Gene location
The human DERL1 gene is located on the long (q) arm of chromosome 8 at region 2 band 4, from base pair 123,013,164 to 123,042,423 (Build GRCh37/hg19) (map).[5]
# Function and mechanism
## Rerouting factor during ER stress
ER stress is caused by an accumulation of unfolded or misfolded proteins in ER and is critical for cell function.[14][15] The accumulation of unfolded and misfolded proteins activates an unfolded protein response (UPR) which regulate the homeostasis of the cell.[16] One of the strategies cells possess to ER stress as a quality control system is the ERAD pathway,[16] by which Derlin-1 is a component of. As a part of an ER membrane protein complex (that includes VIMP, SEL1, HRD1, and HERP) derlin-1 detects misfolded proteins in ER and mediate them for their degradation in the ERAD pathway.[17]
Under ER stress, the carboxyl-terminus region of derlin-1 captures specific misfolded proteins in the ER lumen.[18] Derlin-1 also interacts with VIMP, an ER membrane protein that recruits the cytosolic ATPase p97 and its cofactor.[4] The interaction of derlin-1 with p97 via VIMP is essential for export of misfolded proteins. p97 is required for the transport of the misfolded proteins through the ER membrane and back to the cytosolic side for their degradation.[19] This process is referred to as retrotranslocation. Hence, one of the functions of derlin-1 is to reroute specific misfolded protein to the cytosol for their degradation.[2][4][18] Prior to the cytosolic degradation, the retrotranslocated misfolded proteins interacts with HRDI E3 ubiquitin ligase.[18] This ligase ubiquitinates the misfolded proteins promoting their degradation in the cytosol by the ubiquitin-protease system (UPS).[18] Currently, the molecular mechanism by which derlin-1 reroutes the misfolded proteins from ER to their degradation are not fully understood.
# Clinical significance
Derlin 1 (DERL1) is up-regulated in metastatic canine mammary tumors as part of the unfolded protein response.[20][21][22]
# Interactions
Derlin-1 has been shown to interact with the following proteins:
- HRD1[18]
- VIMP[4]
- US11[4] | https://www.wikidoc.org/index.php/Derlin-1 | |
cfbc61939ddf917344d5616e17251ffd7ffea028 | wikidoc | Desonide | Desonide
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Desonide is a corticosteroid that is FDA approved for the treatment of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. Common adverse reactions include contact dermatitis, dry skin, pruritus, stinging of skin, burning sensation, Irritation symptom.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Dermatoses
- Dosing information
- Desonide cream or ointment should be applied to the affected areas as a thin film two or four times daily depending on the severity of the condition.
- As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within two weeks, reassessment of diagnosis may be necessary.
- Desonide cream and ointment should not be used with occlusive dressings.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of desonide in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of desonide in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness in pediatric patients have not been established
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of desonide in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of desonide in pediatric patients.
# Contraindications
Desonide cream and ointment are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparations.
# Warnings
### General
Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.
Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving superpotent corticosteroids should not be treated for more than two weeks at a time and only small areas should be treated at any one time due to the increased risk of HPA suppressions.
One of ten patients treated for one week under occlusion (30% of body surface) with Desonide Cream, 0.05% developed HPA axis suppression as determined by metapyrone testing. No specific studies relevant to potential HPA suppression have been conducted with desonide Ointment, 0.05%.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios .
If irritation develops, desonide cream or ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of desonide cream or ointment should be discontinued until the infection has been adequately controlled.
Desonide Cream, 0.05% and Ointment, 0.05% should not be used in the presence of infection at the treatment site, hypersensitivity to corticosteroids, or pre-existing skin atrophy. Desonide Cream, 0.05% and Ointment, 0.05% should not be used in the eyes. FOR EXTERNAL USE ONLY.
Laboratory Tests
The following tests may be helpful in evaluating patients for HPA axis suppression:
- ACTH stimulation test
- A.M. plasma cortisol test
- Urinary free cortisol test
# Adverse Reactions
## Clinical Trials Experience
In controlled clinical trials, the total incidence of adverse reactions associated with the use of desonide Cream, 0.05% was approximately 1% and desonide ointment, 0.05% was approximately 6%. The adverse reactions for desonide Cream, 0.05% were pruritus, pain, folliculitis, rash, peripheral edema, pustular rash, sweating, erythema, irritation, and burning. Laboratory abnormalities were found in 3% of the patients. These were hyperglycemia (2%) and liver function abnormality (1%). The adverse reactions for desonide Ointment, 0.05% were erythema, induration, pruritus, irritation, oiliness, and peripheral edema.
The following additional local adverse reactions have been reported infrequently with other topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in approximate decreasing order of occurrence: dryness, folliculitis, acneiform eruptions, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria, burning and hypopigmentation.
## Postmarketing Experience
FDA package insert for desonide contains no information regarding postmarketing experience .
# Drug Interactions
FDA package insert for desonide contains no information regarding drug Interaction.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. Animal reproductive studies have not been conducted with desonide cream or ointment. It is also not known whether desonide cream or ointment can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. There are no adequate and well-controlled studies in pregnant women. Desonide cream or ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Desonide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Desonide during labor and delivery.
### Nursing Mothers
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when desonide cream or ointment is administered to a nursing woman.
### Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment.
Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.
HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
### Geriatic Use
There is no FDA guidance on the use of Desonide in geriatric settings.
### Gender
There is no FDA guidance on the use of Desonide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Desonide with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Desonide in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Desonide in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Desonide in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Desonide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Applied to the affected area.
### Monitoring
FDA package insert for desonide contains no information regarding drug monitoring.
# IV Compatibility
There is limited information about the IV compatibility.
# Overdosage
Topically applied desonide cream and ointment can be absorbed in sufficient amounts to produce systemic effects.
# Pharmacology
## Mechanism of Action
Like other topical corticosteroids, desonide has anti-inflammatory, antipruritic and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
## Structure
Desonide Cream, 0.05% and Ointment, 0.05% contain desonide (Pregna-1,4-diene-3,20-dione,11,21-dihydroxy-16,17--,(11β, 16α-)) a synthetic corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and anti pruritic agents.
Chemically, desonide is C24H32O6. It has the following structural formula:
The molecular weight of desonide is 416.51. It is a white to off-white odorless powder which is soluble in methanol and practically insoluble in water.
Each gram of desonide Cream, 0.05% contains 0.5 mg of desonide in a compatible vehicle buffered to the pH range of normal skin. It contains aluminum acetate basic, cetearyl alcohol/SLS/SCS, glycerin, mineral oil, purified water, white petrolatum and white wax. It is preserved with methylparaben.
Each gram of desonide ointment, 0.05% contains 0.5 mg of desonide in an ointment base consisting of mineral oil and white petrolatum. It is a smooth, uniform petrolatum-type ointment.
## Pharmacodynamics
There is limited information regarding Desonide Pharmacodynamics in the drug label.
## Pharmacokinetics
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone for up to 24 hours have not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Studies performed with desonide cream and ointment indicate that they are in the low range of potency as compared with other topical corticosteroids.
## Nonclinical Toxicology
Long-term animal studies have not been performed to evaluate the carcinogenic, mutagenic, or fertility impairment potential of Desonide Cream, 0.05% and Ointment, 0.05%.
# Clinical Studies
FDA package insert for desonide contains no information regarding clinical studies.
# How Supplied
Desonide Cream 0.05% is supplied in 15 g (NDC 51672-1280-1) and 60 g (NDC 51672-1280-3) tubes.
Desonide Ointment 0.05% is supplied in 15 g (NDC 51672-1281-1) and 60 g (NDC 51672-1281-3) tubes.
## Storage
Store at 20°- 25°C (68°- 77°F) . Protect from freezing.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients using topical corticosteroids should receive the following information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.
2. This medication should not be used for any disorder other than that for which it was prescribed.
3. The treated skin area should not be bandaged, or otherwise covered or wrapped, so as to be occlusive unless directed by the physician.
4. Patients should report to their physician any signs of local adverse reactions.
# Precautions with Alcohol
Alcohol-Desonide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Desowen
- LoKara
- Tridesilon
- Verdeso
- Desonate
# Look-Alike Drug Names
There is limited information about the look alike drug names.
# Drug Shortage Status
# Price | Desonide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2] ;Aparna Vuppala, M.B.B.S. [3]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Desonide is a corticosteroid that is FDA approved for the treatment of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. Common adverse reactions include contact dermatitis, dry skin, pruritus, stinging of skin, burning sensation, Irritation symptom.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Dermatoses
- Dosing information
- Desonide cream or ointment should be applied to the affected areas as a thin film two or four times daily depending on the severity of the condition.
- As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within two weeks, reassessment of diagnosis may be necessary.
- Desonide cream and ointment should not be used with occlusive dressings.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of desonide in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of desonide in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness in pediatric patients have not been established
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of desonide in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of desonide in pediatric patients.
# Contraindications
Desonide cream and ointment are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparations.
# Warnings
### General
Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.
Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving superpotent corticosteroids should not be treated for more than two weeks at a time and only small areas should be treated at any one time due to the increased risk of HPA suppressions.
One of ten patients treated for one week under occlusion (30% of body surface) with Desonide Cream, 0.05% developed HPA axis suppression as determined by metapyrone testing. No specific studies relevant to potential HPA suppression have been conducted with desonide Ointment, 0.05%.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios .
If irritation develops, desonide cream or ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of desonide cream or ointment should be discontinued until the infection has been adequately controlled.
Desonide Cream, 0.05% and Ointment, 0.05% should not be used in the presence of infection at the treatment site, hypersensitivity to corticosteroids, or pre-existing skin atrophy. Desonide Cream, 0.05% and Ointment, 0.05% should not be used in the eyes. FOR EXTERNAL USE ONLY.
Laboratory Tests
The following tests may be helpful in evaluating patients for HPA axis suppression:
- ACTH stimulation test
- A.M. plasma cortisol test
- Urinary free cortisol test
# Adverse Reactions
## Clinical Trials Experience
In controlled clinical trials, the total incidence of adverse reactions associated with the use of desonide Cream, 0.05% was approximately 1% and desonide ointment, 0.05% was approximately 6%. The adverse reactions for desonide Cream, 0.05% were pruritus, pain, folliculitis, rash, peripheral edema, pustular rash, sweating, erythema, irritation, and burning. Laboratory abnormalities were found in 3% of the patients. These were hyperglycemia (2%) and liver function abnormality (1%). The adverse reactions for desonide Ointment, 0.05% were erythema, induration, pruritus, irritation, oiliness, and peripheral edema.
The following additional local adverse reactions have been reported infrequently with other topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in approximate decreasing order of occurrence: dryness, folliculitis, acneiform eruptions, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria, burning and hypopigmentation.
## Postmarketing Experience
FDA package insert for desonide contains no information regarding postmarketing experience .
# Drug Interactions
FDA package insert for desonide contains no information regarding drug Interaction.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. Animal reproductive studies have not been conducted with desonide cream or ointment. It is also not known whether desonide cream or ointment can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. There are no adequate and well-controlled studies in pregnant women. Desonide cream or ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Desonide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Desonide during labor and delivery.
### Nursing Mothers
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when desonide cream or ointment is administered to a nursing woman.
### Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment.
Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.
HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
### Geriatic Use
There is no FDA guidance on the use of Desonide in geriatric settings.
### Gender
There is no FDA guidance on the use of Desonide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Desonide with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Desonide in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Desonide in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Desonide in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Desonide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Applied to the affected area.
### Monitoring
FDA package insert for desonide contains no information regarding drug monitoring.
# IV Compatibility
There is limited information about the IV compatibility.
# Overdosage
Topically applied desonide cream and ointment can be absorbed in sufficient amounts to produce systemic effects.
# Pharmacology
## Mechanism of Action
Like other topical corticosteroids, desonide has anti-inflammatory, antipruritic and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
## Structure
Desonide Cream, 0.05% and Ointment, 0.05% contain desonide (Pregna-1,4-diene-3,20-dione,11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-,(11β, 16α-)) a synthetic corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and anti pruritic agents.
Chemically, desonide is C24H32O6. It has the following structural formula:
The molecular weight of desonide is 416.51. It is a white to off-white odorless powder which is soluble in methanol and practically insoluble in water.
Each gram of desonide Cream, 0.05% contains 0.5 mg of desonide in a compatible vehicle buffered to the pH range of normal skin. It contains aluminum acetate basic, cetearyl alcohol/SLS/SCS, glycerin, mineral oil, purified water, white petrolatum and white wax. It is preserved with methylparaben.
Each gram of desonide ointment, 0.05% contains 0.5 mg of desonide in an ointment base consisting of mineral oil and white petrolatum. It is a smooth, uniform petrolatum-type ointment.
## Pharmacodynamics
There is limited information regarding Desonide Pharmacodynamics in the drug label.
## Pharmacokinetics
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone for up to 24 hours have not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Studies performed with desonide cream and ointment indicate that they are in the low range of potency as compared with other topical corticosteroids.
## Nonclinical Toxicology
Long-term animal studies have not been performed to evaluate the carcinogenic, mutagenic, or fertility impairment potential of Desonide Cream, 0.05% and Ointment, 0.05%.
# Clinical Studies
FDA package insert for desonide contains no information regarding clinical studies.
# How Supplied
Desonide Cream 0.05% is supplied in 15 g (NDC 51672-1280-1) and 60 g (NDC 51672-1280-3) tubes.
Desonide Ointment 0.05% is supplied in 15 g (NDC 51672-1281-1) and 60 g (NDC 51672-1281-3) tubes.
## Storage
Store at 20°- 25°C (68°- 77°F) . Protect from freezing.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients using topical corticosteroids should receive the following information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.
2. This medication should not be used for any disorder other than that for which it was prescribed.
3. The treated skin area should not be bandaged, or otherwise covered or wrapped, so as to be occlusive unless directed by the physician.
4. Patients should report to their physician any signs of local adverse reactions.
# Precautions with Alcohol
Alcohol-Desonide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Desowen
- LoKara
- Tridesilon
- Verdeso
- Desonate
# Look-Alike Drug Names
There is limited information about the look alike drug names.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Desonide | |
a843c4750d56555c30b7a63fd0f57468977fe8a3 | wikidoc | Detritus | Detritus
# Overview
In biology, detritus is non-living particulate organic material (as opposed to dissolved organic material). It typically includes the bodies of dead organisms or fragments of organisms or fecal material. Detritus is normally colonized by communities of microorganisms which act to decompose (or remineralize) the material.
- In terrestrial ecosystems, the term refers to litter on the soil surface as well as organic matter intermixed with soil.
- In aquatic ecosystems, the term refers to organic material found suspended in water. Together with plankton, detritus is an important constituent of seston (materials in suspension), and may also accumulate at the base of a water column.
# General theory
Dead plants or animals, material derived from body tissues such as skin cast off during moulting, and matter derived from organisms in the form of excreta all gradually lose their form, due to both physical processes and the action of decomposers, such as bacteria and fungi. Decomposition, the process through which organic matter is decomposed, takes place in many stages. Materials like proteins, lipids and sugars with low molecular weight are rapidly consumed and absorbed by micro-organisms and organisms that feed on dead matter. Other compounds, such as complex carbohydrates are broken down more slowly. In addition, the purpose of the various micro-organisms involved is not to break down these materials but to use them to gain the resources they require for their own survival and proliferation, and they are merely breaking them down as part of that process. Accordingly, at the same time that the materials of plants and animals are being broken down, the materials (biomass) making up the bodies of the micro-organisms are built up by a process of assimilation. When micro-organisms die, fine organic particles are produced, and if these are eaten by small animals which feed on micro-organisms, they will collect inside their intestines, and change shape into large pellets of dung. As a result of this process, most of the materials from dead organisms disappears from view and is not obviously present in any recognisable form, but is in fact present in the form of a combination of fine organic particles and the organisms using them as nutrients. This combination is detritus.
In ecosystems on land, detritus is deposited on the surface of the ground, taking forms such as the humic soil beneath a layer of fallen leaves. In aquatic ecosystems, most detritus is suspended in water, and gradually settles. In particular, many different types of material are collected together by currents, and much material settles in slowly-flowing areas.
Much detritus is used as a source of nutrition for animals. In particular, many bottom-dwelling animals (benthos) living in mud flats feed in this way. In particular, since excreta are materials which other animals do not need, whatever energy value they might have, they are often unbalanced as a source of nutrients, and are not suitable as a source of nutrition on their own. However, there are many micro-organisms which multiply in natural environments. These micro-organisms do not simply absorb nutrients from these particles, but also shape their own bodies so that they can take the resources they lack from the area around them, and this allows them to make good use of excreta as a source of nutrients. In practical terms, the most important constituents of detritus are complex carbohydrates, which are persistent (difficult to break down), and the micro-organisms which multiply using these absorb carbon from the detritus, and materials such as nitrogen and phosphorus from the water in their environment to synthesise the components of their own cells.
A characteristic type of food chain called the detritus cycle takes place involving detritus feeders (detritivores), detritus and the micro-organisms that multiply on it. For example, mud flats are inhabited by many univalves which are detritus feeders, such as moon shells. When these detritus feeders take in detritus with micro-organisms multiplying on it, they mainly break down and absorb the micro-organisms, which are rich in proteins, and excrete the detritus, which is mostly complex carbohydrates, having hardly broken it down at all. At first this dung is a poor source of nutrition, and so univalves pay no attention to it, but after several days, micro-organisms begin to multiply on it again, its nutritional balance improves, and so they eat it again. Through this process of eating the detritus many times over and harvesting the micro-organisms from it, the detritus thins out, becomes fractured and becomes easier for the micro-organisms to use, and so the complex carbohydrates are also steadily broken down and disappear over time.
What is left behind by the detritivores is then further broken down and recycled by decomposers, such as bacteria and fungi.
This detritus cycle plays a large part in the so-called purification process, whereby organic materials carried in by rivers is broken down and disappears, and an extremely important part in the breeding and growth of marine resources. In ecosystems on land, far more essential material is broken down as dead material passing through the detritus chain than is broken down by being eaten by animals in a living state. In both land and aquatic ecosystems, the role played by detritus is too large to ignore.
The primary microorganisms that break down matter are called mesophilic (microorganisms thriving at medium temperatures). They cause a lot of heat which is why compost becomes warm after a while.
# Aquatic ecosystems
In contrast to land ecosystems, dead materials and excreta in aquatic ecosystems do not settle immediately, and the finer the particles involved are, the longer they tend to take.
## Consumers
There are an extremely large number of detritus feeders in water. After all, a large quantity of material is carried in by water currents. Even if an organism stays in a fixed position, as long as it has a system for filtering water, it will be able to obtain enough food to get by. Many rooted organisms survive in this way, using developed gills or tentacles to filter the water to take in food, a process known as filter feeding.
Another more widely used method of feeding, which also incorporates filter feeding, is a system where an organism secretes mucus to catch the detritus in lumps, and then carries these to its mouth using an area of cilia. This is called mucus feeding.
Many organisms, including sea slugs and serpent's starfish, scoop up the detritus which has settled on the water bed. Bivalves which live inside the water bed do not simply suck in water through their tubes, but also extend them to fish for detritus on the surface of the bed.
## Producers
In contrast, from the point of view of organisms using photosynthesis, such as plants and plankton, detritus reduces the transparency of the water and gets in the way of their photosynthesis. However, given that they also require a supply of nutrient salts, in other words fertilizer for photosynthesis, their relationship with detritus is a complex one.
In land ecosystems, the waste products of plants and animals collect mainly on the ground (or on the surfaces of trees), and as decomposition proceeds, plants are supplied with fertiliser in the form of inorganic salts. However, in water, relatively little waste collects on the water bed, and so the progress of decomposition in water takes a more important role. However, investigating the level of inorganic salts in sea ecosystems shows that, unless there is an especially large supply, the quantity increases from winter to spring but is normally extremely low in summer. In line with this, the quantity of seaweed present reaches a peak in early summer, and then decreases. This is thought to be because organisms like plants grow quickly in warm periods and the quantity of inorganic salts is not enough to keep up with the demand. In other words, during winter, plant-like organisms are inactive and collect fertiliser, but if the temperature rises to some extent, they use this up in a very short period.
However, it is not the case that their productivity falls during the warmest periods. Organisms such as dinoflagellate have mobility, the ability to take in solid food, and the ability to photosynthesise. This type of micro-organism can take in substances such as detritus to grow, without waiting for it to be broken down into fertiliser.
# Aquariums
In recent years, the word detritus has also come to be used in relation to aquariums (the word "aquarium" is a general term for any installation for keeping aquatic animals).
When animals such as fish are kept in an aquarium, substances such as excreta, mucus and dead skin cast off during moulting are produced by the animals and, naturally, generate detritus, and are continually broken down by micro-organisms.
If detritus is left unattended, it dirties the inside of the water tank, and harms the health of the animals inside. Sea-dwelling animals, in particular, have little resistance to the toxins that are produced by the decomposition of detritus. Modern sealife aquariums often use the Berlin system, which employs a piece of equipment called a protein skimmer, which produces air bubbles which the detritus adheres to, and forces it outside the tank before it decomposes, and also a highly porous type of natural rock called live rock where many bentos and bacteria live (hermatype which has been dead for some time is often used), which causes the detritus-feeding bentos and micro-organisms to undergo a detritus cycle. The Monaco system, where an anaerobic layer is created in the tank, to denitrify the organic compounds in the tank, and also the other nitrogen compounds, so that the decomposition process continues until the stage where water, carbon dioxide and nitrogen are produced, has also been implemented.
Initially, the filtration systems in water tanks often worked as the name suggests, using a physical filter to remove foreign substances in the water. Following this, the standard method for maintaining the water quality was to convert ammonium or nitrates in excreta, which have a high degree of neurotoxicity, but the combination of detritus feeders, detritus and micro-organisms has now brought aquarium technology to a still higher level.
# Sources
- Much of this article was translated from the equivalent article in the Japanese-language Wikipedia, as it was on September 1, 2006. | Detritus
# Overview
In biology, detritus is non-living particulate organic material (as opposed to dissolved organic material). It typically includes the bodies of dead organisms or fragments of organisms or fecal material. Detritus is normally colonized by communities of microorganisms which act to decompose (or remineralize) the material.
- In terrestrial ecosystems, the term refers to litter on the soil surface as well as organic matter intermixed with soil.
- In aquatic ecosystems, the term refers to organic material found suspended in water. Together with plankton, detritus is an important constituent of seston (materials in suspension), and may also accumulate at the base of a water column.
# General theory
Dead plants or animals, material derived from body tissues such as skin cast off during moulting, and matter derived from organisms in the form of excreta all gradually lose their form, due to both physical processes and the action of decomposers, such as bacteria and fungi. Decomposition, the process through which organic matter is decomposed, takes place in many stages. Materials like proteins, lipids and sugars with low molecular weight are rapidly consumed and absorbed by micro-organisms and organisms that feed on dead matter. Other compounds, such as complex carbohydrates are broken down more slowly. In addition, the purpose of the various micro-organisms involved is not to break down these materials but to use them to gain the resources they require for their own survival and proliferation, and they are merely breaking them down as part of that process. Accordingly, at the same time that the materials of plants and animals are being broken down, the materials (biomass) making up the bodies of the micro-organisms are built up by a process of assimilation. When micro-organisms die, fine organic particles are produced, and if these are eaten by small animals which feed on micro-organisms, they will collect inside their intestines, and change shape into large pellets of dung. As a result of this process, most of the materials from dead organisms disappears from view and is not obviously present in any recognisable form, but is in fact present in the form of a combination of fine organic particles and the organisms using them as nutrients. This combination is detritus.
In ecosystems on land, detritus is deposited on the surface of the ground, taking forms such as the humic soil beneath a layer of fallen leaves. In aquatic ecosystems, most detritus is suspended in water, and gradually settles. In particular, many different types of material are collected together by currents, and much material settles in slowly-flowing areas.
Much detritus is used as a source of nutrition for animals. In particular, many bottom-dwelling animals (benthos) living in mud flats feed in this way. In particular, since excreta are materials which other animals do not need, whatever energy value they might have, they are often unbalanced as a source of nutrients, and are not suitable as a source of nutrition on their own. However, there are many micro-organisms which multiply in natural environments. These micro-organisms do not simply absorb nutrients from these particles, but also shape their own bodies so that they can take the resources they lack from the area around them, and this allows them to make good use of excreta as a source of nutrients. In practical terms, the most important constituents of detritus are complex carbohydrates, which are persistent (difficult to break down), and the micro-organisms which multiply using these absorb carbon from the detritus, and materials such as nitrogen and phosphorus from the water in their environment to synthesise the components of their own cells.
A characteristic type of food chain called the detritus cycle takes place involving detritus feeders (detritivores), detritus and the micro-organisms that multiply on it. For example, mud flats are inhabited by many univalves which are detritus feeders, such as moon shells. When these detritus feeders take in detritus with micro-organisms multiplying on it, they mainly break down and absorb the micro-organisms, which are rich in proteins, and excrete the detritus, which is mostly complex carbohydrates, having hardly broken it down at all. At first this dung is a poor source of nutrition, and so univalves pay no attention to it, but after several days, micro-organisms begin to multiply on it again, its nutritional balance improves, and so they eat it again. Through this process of eating the detritus many times over and harvesting the micro-organisms from it, the detritus thins out, becomes fractured and becomes easier for the micro-organisms to use, and so the complex carbohydrates are also steadily broken down and disappear over time.
What is left behind by the detritivores is then further broken down and recycled by decomposers, such as bacteria and fungi.
This detritus cycle plays a large part in the so-called purification process, whereby organic materials carried in by rivers is broken down and disappears, and an extremely important part in the breeding and growth of marine resources. In ecosystems on land, far more essential material is broken down as dead material passing through the detritus chain than is broken down by being eaten by animals in a living state. In both land and aquatic ecosystems, the role played by detritus is too large to ignore.
The primary microorganisms that break down matter are called mesophilic (microorganisms thriving at medium temperatures). They cause a lot of heat which is why compost becomes warm after a while.
# Aquatic ecosystems
In contrast to land ecosystems, dead materials and excreta in aquatic ecosystems do not settle immediately, and the finer the particles involved are, the longer they tend to take.
## Consumers
There are an extremely large number of detritus feeders in water. After all, a large quantity of material is carried in by water currents. Even if an organism stays in a fixed position, as long as it has a system for filtering water, it will be able to obtain enough food to get by. Many rooted organisms survive in this way, using developed gills or tentacles to filter the water to take in food, a process known as filter feeding.
Another more widely used method of feeding, which also incorporates filter feeding, is a system where an organism secretes mucus to catch the detritus in lumps, and then carries these to its mouth using an area of cilia. This is called mucus feeding.
Many organisms, including sea slugs and serpent's starfish, scoop up the detritus which has settled on the water bed. Bivalves which live inside the water bed do not simply suck in water through their tubes, but also extend them to fish for detritus on the surface of the bed.
## Producers
In contrast, from the point of view of organisms using photosynthesis, such as plants and plankton, detritus reduces the transparency of the water and gets in the way of their photosynthesis. However, given that they also require a supply of nutrient salts, in other words fertilizer for photosynthesis, their relationship with detritus is a complex one.
In land ecosystems, the waste products of plants and animals collect mainly on the ground (or on the surfaces of trees), and as decomposition proceeds, plants are supplied with fertiliser in the form of inorganic salts. However, in water, relatively little waste collects on the water bed, and so the progress of decomposition in water takes a more important role. However, investigating the level of inorganic salts in sea ecosystems shows that, unless there is an especially large supply, the quantity increases from winter to spring but is normally extremely low in summer. In line with this, the quantity of seaweed present reaches a peak in early summer, and then decreases. This is thought to be because organisms like plants grow quickly in warm periods and the quantity of inorganic salts is not enough to keep up with the demand. In other words, during winter, plant-like organisms are inactive and collect fertiliser, but if the temperature rises to some extent, they use this up in a very short period.
However, it is not the case that their productivity falls during the warmest periods. Organisms such as dinoflagellate have mobility, the ability to take in solid food, and the ability to photosynthesise. This type of micro-organism can take in substances such as detritus to grow, without waiting for it to be broken down into fertiliser.
# Aquariums
In recent years, the word detritus has also come to be used in relation to aquariums (the word "aquarium" is a general term for any installation for keeping aquatic animals).
When animals such as fish are kept in an aquarium, substances such as excreta, mucus and dead skin cast off during moulting are produced by the animals and, naturally, generate detritus, and are continually broken down by micro-organisms.
If detritus is left unattended, it dirties the inside of the water tank, and harms the health of the animals inside. Sea-dwelling animals, in particular, have little resistance to the toxins that are produced by the decomposition of detritus. Modern sealife aquariums often use the Berlin system, which employs a piece of equipment called a protein skimmer, which produces air bubbles which the detritus adheres to, and forces it outside the tank before it decomposes, and also a highly porous type of natural rock called live rock where many bentos and bacteria live (hermatype which has been dead for some time is often used), which causes the detritus-feeding bentos and micro-organisms to undergo a detritus cycle. The Monaco system, where an anaerobic layer is created in the tank, to denitrify the organic compounds in the tank, and also the other nitrogen compounds, so that the decomposition process continues until the stage where water, carbon dioxide and nitrogen are produced, has also been implemented.
Initially, the filtration systems in water tanks often worked as the name suggests, using a physical filter to remove foreign substances in the water. Following this, the standard method for maintaining the water quality was to convert ammonium or nitrates in excreta, which have a high degree of neurotoxicity, but the combination of detritus feeders, detritus and micro-organisms has now brought aquarium technology to a still higher level.
# Sources
- Much of this article was translated from the equivalent article in the Japanese-language Wikipedia, as it was on September 1, 2006. | https://www.wikidoc.org/index.php/Detritus | |
c00bdc3768e9073b9814e2c7164f2c5a5cba60f4 | wikidoc | Dialysis | Dialysis
For patient information page, click here
# Overview
Chronic kidney disease (CKD) prevalence has an increased rate worldwide due to increased prevalence of diabetes mellitus and hypertension as the leading causes of CKD, increasing life expectancy, and aging of the populations. On the other hand, acute kidney injury requires renal replacement therapy in certain circumstances. Dialysis is an intervention aiming to substitutes for solutes and removing extra fluids to help or substitute the failing kidneys. It is considered as a renal replacement therapy method which is indicated in certain condition depending on severity and chronicity of the underlying condition. In acute setting, refractory increased electrolytes and fluid overload are the most common indications for dialysis. eGFR is the determining factor to initiate dialysis in chronic kidney disease however, uremic symptoms, presence of comorbidities, and nutritional status are important factors influencing nephrologist's judgement to consider early versus late dialysis. In 2010, it is estimated that 2.3-7.1 million patients died of end stage renal disease (ESRD) without having access to dialysis. In 2010, 2.62 million people received dialysis worldwide and the need for dialysis was projected to double by 2030. Timely initiating dialysis could save lives, prevent complications, and decrease comorbidities. Patients should be educated about the process and goals of this method of treatment.
# Classification
There are two main types of dialysis, hemodialysis and peritoneal dialysis. The mode of dialysis should be selected based on patients preference, chronicity of disease, underlying disease, comorbidities, and availability of the modality.
# Indications
The decision to initiate dialysis or hemofiltration in patients with renal failure can depend on several factors. The following factors are the most important aspects that nephrologists consider in every patient individually to initiate dialysis.
## Uremic Symptoms
The following table describe the uremic symptoms and signs according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines.
## Nutritional Status
Nutritional status of CKD patients should be assessed frequently. Many factors could be considered as indicator, such as normalized protein equivalent of nitrogen appearance (nPNA), subjective global assessment (SGA), assessment of body composition by bioelectrical impedance analysis (BIA), lean body mass, and serum albumin level. Deterioration of nutritional status which is considered as protein energy malnutrition, resistant to dietary supplementation is an indication for dialysis.
## Comorbidities
Conditions like volume overload and heart failure may result in clinical deterioration in CKD patients regardless of eGFR level. Accordingly, these conditions must be assessed in every patients for early diagnosis and dialysis initiation.
## Metabolic Derangements
Persistent metabolic and electrolyte derangements despite medical therapy are conditions that may require incident dialysis in acute settings. They include hyperkalemia, metabolic acidosis, and dialysable drug intoxications, such as lithium or aspirin toxicity.
## National Kidney Foundation Recommendation
Summary the recommendation from NKF KDOQI 2015 guidelines for dialysis indicates the following indications for initiating dialysis:
- Signs and/or symptoms associated with uremia
- Evidences of protein-energy wasting
- Inability to safely manage metabolic abnormalities and/or volume overload with medical therapy | Dialysis
For patient information page, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]
# Overview
Chronic kidney disease (CKD) prevalence has an increased rate worldwide due to increased prevalence of diabetes mellitus and hypertension as the leading causes of CKD, increasing life expectancy, and aging of the populations. On the other hand, acute kidney injury requires renal replacement therapy in certain circumstances. Dialysis is an intervention aiming to substitutes for solutes and removing extra fluids to help or substitute the failing kidneys. It is considered as a renal replacement therapy method which is indicated in certain condition depending on severity and chronicity of the underlying condition. In acute setting, refractory increased electrolytes and fluid overload are the most common indications for dialysis. eGFR is the determining factor to initiate dialysis in chronic kidney disease however, uremic symptoms, presence of comorbidities, and nutritional status are important factors influencing nephrologist's judgement to consider early versus late dialysis. In 2010, it is estimated that 2.3-7.1 million patients died of end stage renal disease (ESRD) without having access to dialysis. In 2010, 2.62 million people received dialysis worldwide and the need for dialysis was projected to double by 2030.[1] Timely initiating dialysis could save lives, prevent complications, and decrease comorbidities. Patients should be educated about the process and goals of this method of treatment.
# Classification
There are two main types of dialysis, hemodialysis and peritoneal dialysis. The mode of dialysis should be selected based on patients preference, chronicity of disease, underlying disease, comorbidities, and availability of the modality.
# Indications
The decision to initiate dialysis or hemofiltration in patients with renal failure can depend on several factors. The following factors are the most important aspects that nephrologists consider in every patient individually to initiate dialysis.
## Uremic Symptoms
The following table describe the uremic symptoms and signs according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines.[2][3]
## Nutritional Status
Nutritional status of CKD patients should be assessed frequently. Many factors could be considered as indicator, such as normalized protein equivalent of nitrogen appearance (nPNA), subjective global assessment (SGA), assessment of body composition by bioelectrical impedance analysis (BIA), lean body mass, and serum albumin level. Deterioration of nutritional status which is considered as protein energy malnutrition, resistant to dietary supplementation is an indication for dialysis.[4][5][6][7][8]
## Comorbidities
Conditions like volume overload and heart failure may result in clinical deterioration in CKD patients regardless of eGFR level. Accordingly, these conditions must be assessed in every patients for early diagnosis and dialysis initiation.[9][10][11]
## Metabolic Derangements
Persistent metabolic and electrolyte derangements despite medical therapy are conditions that may require incident dialysis in acute settings. They include hyperkalemia, metabolic acidosis, and dialysable drug intoxications, such as lithium or aspirin toxicity.
## National Kidney Foundation Recommendation
Summary the recommendation from NKF KDOQI 2015 guidelines for dialysis indicates the following indications for initiating dialysis:
- Signs and/or symptoms associated with uremia
- Evidences of protein-energy wasting
- Inability to safely manage metabolic abnormalities and/or volume overload with medical therapy | https://www.wikidoc.org/index.php/Dialysis | |
c083359b5fb8433169a3ce80608cd689c0cb4cf3 | wikidoc | Diameter | Diameter
In geometry, a diameter (Greek words dia = through and metro = measure) of a circle is any straight line segment that passes through the center of the circle and whose endpoints are on the circle. The diameters are the longest chords of the circle.
In more modern usage, the length of a diameter is also called the diameter. In this sense one speaks of the diameter rather than a diameter, because all diameters of a circle have the same length, this being twice the radius.
For a convex shape in the plane, the diameter is defined to be the largest distance that can be formed between two opposite parallel lines tangent to its boundary, and the width is defined to be the smallest such distance. For a curve of constant width such as the Reuleaux triangle, the width and diameter are the same because all such pairs of parallel tangent lines have the same distance.
The diameter of a connected graph is the distance between the two vertices which are furthest from each other. The distance between two vertices a and b is the length of the shortest path connecting them (for the length of a path, see Graph theory).
The three definitions given above are special cases of a more general definition. The diameter of a subset of a metric space is the least upper bound of the distances between pairs of points in the subset. So, if A is the subset, the diameter is
In medical parlance the diameter of a lesion is the longest line segment whose endpoints are within the lesion.
# Diameter symbol
The symbol or variable for diameter is similar in size and design to ø, the lowercase letter o with stroke. Unicode provides character number 8960 (hexadecimal 2300) for the symbol, which can be encoded in HTML webpages as ⌀ or ⌀. Proper display of this character, however, is unlikely in most situations, as most fonts do not have it included. (Your browser displays ⌀ in the current font.) In most situations the letter ø is acceptable, obtained in Microsoft Windows by holding the key down while entering 0 2 4 8 on the numeric keypad.
It is important not to confuse a diameter symbol (⌀) with the empty set symbol (∅), similar to the uppercase Ø. Phi is sometimes used for diameter, although this seems to come from the fact that the symbols appear similar.
The diameter also refers to the approximate size of the corner of a frame of any given object to the nearest flat surface it represents. | Diameter
In geometry, a diameter (Greek words dia = through and metro = measure) of a circle is any straight line segment that passes through the center of the circle and whose endpoints are on the circle. The diameters are the longest chords of the circle.
In more modern usage, the length of a diameter is also called the diameter. In this sense one speaks of the diameter rather than a diameter, because all diameters of a circle have the same length, this being twice the radius.
For a convex shape in the plane, the diameter is defined to be the largest distance that can be formed between two opposite parallel lines tangent to its boundary, and the width is defined to be the smallest such distance. For a curve of constant width such as the Reuleaux triangle, the width and diameter are the same because all such pairs of parallel tangent lines have the same distance.
The diameter of a connected graph is the distance between the two vertices which are furthest from each other. The distance between two vertices a and b is the length of the shortest path connecting them (for the length of a path, see Graph theory).
The three definitions given above are special cases of a more general definition. The diameter of a subset of a metric space is the least upper bound of the distances between pairs of points in the subset. So, if A is the subset, the diameter is
In medical parlance the diameter of a lesion is the longest line segment whose endpoints are within the lesion.
# Diameter symbol
The symbol or variable for diameter is similar in size and design to ø, the lowercase letter o with stroke. Unicode provides character number 8960 (hexadecimal 2300) for the symbol, which can be encoded in HTML webpages as ⌀ or ⌀. Proper display of this character, however, is unlikely in most situations, as most fonts do not have it included. (Your browser displays ⌀ in the current font.) In most situations the letter ø is acceptable, obtained in Microsoft Windows by holding the [Alt] key down while entering 0 2 4 8 on the numeric keypad.
It is important not to confuse a diameter symbol (⌀) with the empty set symbol (∅), similar to the uppercase Ø. Phi is sometimes used for diameter, although this seems to come from the fact that the symbols appear similar.
The diameter also refers to the approximate size of the corner of a frame of any given object to the nearest flat surface it represents. | https://www.wikidoc.org/index.php/Diameter | |
643a2444dcf987308a17dbf4ab79efcdde838b39 | wikidoc | Diapause | Diapause
Diapause is a physiological state of dormancy with very specific triggering and releasing conditions; there are various definitions and contexts in which the term is used, but its most common application is in arthropods, especially insects. One of the most explicit definitions, covering many of the important features, is the following:
"a neurohormonally mediated, dynamic state of low metabolic activity. Associated with this are reduced morphogenesis, increased resistance to environmental extremes, and altered or reduced behavioral activity. Diapause occurs during a genetically determined stage(s) of metamorphosis, and its full expression develops in a species-specific manner, usually in response to a number of environmental stimuli that precede unfavorable conditions. Once diapause has begun, metabolic activity is suppressed even if conditions favorable for development prevail."
Of primary importance is that diapause is not only induced by specific stimuli, but - once initiated - only certain stimuli are capable of releasing the organism from this state; the latter is essential in distinguishing diapause as a different phenomenon from hibernation, for example.
A similar phenomenon occurs in the seeds or other resting stages of various plants. In the eggs of various vertebrates there is a phenomenon sometimes known as "embryonic diapause", which is also termed "delayed implantation," and is not directly equivalent to the phenomenon in arthropods, though in both cases there is a cessation of metabolic activity.
The definition above specifically includes the phrase "altered or reduced behavioral activity" to accommodate for the related phenomenon of reproductive diapause; this is a physiological condition where the organism itself will remain fully active, including feeding and other routine activities, but the reproductive organs experience a tissue-specific reduction in metabolism (with characteristic triggering and releasing stimuli). This is widespread in insects, including common and well-known species such as the Monarch butterfly. | Diapause
Diapause is a physiological state of dormancy with very specific triggering and releasing conditions; there are various definitions and contexts in which the term is used, but its most common application is in arthropods, especially insects. One of the most explicit definitions, covering many of the important features, is the following:
"a neurohormonally mediated, dynamic state of low metabolic activity. Associated with this are reduced morphogenesis, increased resistance to environmental extremes, and altered or reduced behavioral activity. Diapause occurs during a genetically determined stage(s) of metamorphosis, and its full expression develops in a species-specific manner, usually in response to a number of environmental stimuli that precede unfavorable conditions. Once diapause has begun, metabolic activity is suppressed even if conditions favorable for development prevail."[1]
Of primary importance is that diapause is not only induced by specific stimuli, but - once initiated - only certain stimuli are capable of releasing the organism from this state; the latter is essential in distinguishing diapause as a different phenomenon from hibernation, for example.
A similar phenomenon occurs in the seeds or other resting stages of various plants. In the eggs of various vertebrates there is a phenomenon sometimes known as "embryonic diapause", which is also termed "delayed implantation," and is not directly equivalent to the phenomenon in arthropods, though in both cases there is a cessation of metabolic activity.
The definition above specifically includes the phrase "altered or reduced behavioral activity" to accommodate for the related phenomenon of reproductive diapause; this is a physiological condition where the organism itself will remain fully active, including feeding and other routine activities, but the reproductive organs experience a tissue-specific reduction in metabolism (with characteristic triggering and releasing stimuli). This is widespread in insects, including common and well-known species such as the Monarch butterfly.[2] | https://www.wikidoc.org/index.php/Diapause | |
a8c764f154f1e905e6a88f35d13a45fb4064ec87 | wikidoc | Diastole | Diastole
Diastole is the period of time when the heart relaxes after contraction. Ventricular diastole is when the ventricles are relaxing, while atrial diastole is when the atria are relaxing.
# Inside the heart
During ventricular diastole, the pressure in the (left and right) ventricles drops from the peak that it reaches in systole. When the pressure in the left ventricle drops to below the pressure in the left atrium, the mitral valve (bicuspid valve) opens, causing accumulated blood from the atrium to flow into the ventricle.
# Inside the arteries
The adjective "diastolic" is used to refer to the relaxation of the heart between muscle contractions. It is used to describe portions of the cardiac cycle related to contraction. More typically it is used as one component of measurement of blood pressure. "Diastolic pressure" refers to the lowest pressure within the arterial blood stream occurring during each heart beat. The other component of blood pressure is systolic pressure, which refers to the highest arterial pressure during each heart beat. When stating blood pressure, systole and then diastole is mentioned; for example: 120/80. | Diastole
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Diastole is the period of time when the heart relaxes after contraction. Ventricular diastole is when the ventricles are relaxing, while atrial diastole is when the atria are relaxing.
# Inside the heart
During ventricular diastole, the pressure in the (left and right) ventricles drops from the peak that it reaches in systole. When the pressure in the left ventricle drops to below the pressure in the left atrium, the mitral valve (bicuspid valve) opens, causing accumulated blood from the atrium to flow into the ventricle.
# Inside the arteries
The adjective "diastolic" is used to refer to the relaxation of the heart between muscle contractions. It is used to describe portions of the cardiac cycle related to contraction. More typically it is used as one component of measurement of blood pressure. "Diastolic pressure" refers to the lowest pressure within the arterial blood stream occurring during each heart beat. The other component of blood pressure is systolic pressure, which refers to the highest arterial pressure during each heart beat. When stating blood pressure, systole and then diastole is mentioned; for example: 120/80. | https://www.wikidoc.org/index.php/Diastole | |
fccc74ca5bb0b77f3c49dea141e4000a6c2b6208 | wikidoc | Diazinon | Diazinon
# Overview
Diazinon (O,O-diethyl-O-(2-isopropyl-6-methyl-pyrimidine-4-yl)phosphorothioate), a colorless to dark brown liquid, is a thiophosphoric acid developed in 1952 by Ciba-Geigy, a Swiss chemical company (later Novartis and then Syngenta). It is a nonsystemic organophosphate insecticide formerly used to control cockroaches, silverfish, ants, and fleas in residential, non-food buildings. Bait was used to control scavenger wasps in the western U.S. Residential uses of diazinon were cancelled in 2004; it is still approved for agricultural uses.
Diazinon kills insects by inhibiting acetylcholinesterase, an enzyme needed for proper nervous system function. Diazinon has a low persistence in soil. The half-life is 2 to 6 weeks . The symptoms associated with diazinon poisoning in humans include weakness, headaches, tightness in the chest, blurred vision, nonreactive pinpoint pupils, excessive salivation, sweating, nausea, vomiting, diarrhea, abdominal cramps, and slurred speech.
In 1988, the Environmental Protection Agency prohibited the use of Diazinon on golf courses and sod farms because of decimation of bird flocks that congregated in these areas. In the United States as of December 31, 2004, it became unlawful to sell diazinon outdoor, non-agricultural products. It is still legal for consumers to use diazinon products purchased before this date, provided that they follow all label directions and precautions.
Among cultivators of carnivorous plants, diazinon is known as the most effective systemic insecticide, capable of eradicating severe infestations of aphids, mealybugs and other sucking parasites while leaving the plant unharmed. For cultivators unable to obtain diazinon, Malathion and Acephate (Orthene) have been reported as less effective substitutes. | Diazinon
# Overview
Diazinon (O,O-diethyl-O-(2-isopropyl-6-methyl-pyrimidine-4-yl)phosphorothioate), a colorless to dark brown liquid, is a thiophosphoric acid developed in 1952 by Ciba-Geigy, a Swiss chemical company (later Novartis and then Syngenta). It is a nonsystemic organophosphate insecticide formerly used to control cockroaches, silverfish, ants, and fleas in residential, non-food buildings. Bait was used to control scavenger wasps in the western U.S. Residential uses of diazinon were cancelled in 2004; it is still approved for agricultural uses.
Diazinon kills insects by inhibiting acetylcholinesterase, an enzyme needed for proper nervous system function. Diazinon has a low persistence in soil. The half-life is 2 to 6 weeks [1]. The symptoms associated with diazinon poisoning in humans include weakness, headaches, tightness in the chest, blurred vision, nonreactive pinpoint pupils, excessive salivation, sweating, nausea, vomiting, diarrhea, abdominal cramps, and slurred speech.
In 1988, the Environmental Protection Agency prohibited the use of Diazinon on golf courses and sod farms because of decimation of bird flocks that congregated in these areas. In the United States as of December 31, 2004, it became unlawful to sell diazinon outdoor, non-agricultural products. It is still legal for consumers to use diazinon products purchased before this date, provided that they follow all label directions and precautions.
Among cultivators of carnivorous plants, diazinon is known as the most effective systemic insecticide, capable of eradicating severe infestations of aphids, mealybugs and other sucking parasites while leaving the plant unharmed. For cultivators unable to obtain diazinon, Malathion and Acephate (Orthene) have been reported as less effective substitutes. | https://www.wikidoc.org/index.php/Diazinon | |
24b79d7ff59e9d0e6f5b0fd7d25283fe42bdf2d8 | wikidoc | Diborane | Diborane
Diborane is the chemical compound with the formula B2H6. It is a colorless gas at room temperature with a repulsively sweet odor. B2H6 mixes well with air, easily forming explosive mixtures. Diborane will ignite spontaneously in moist air at room temperature. Synonyms include boroethane, boron hydride, and diboron hexahydride.
B2H6 is a key boron compound with a variety of applications. The compound is endothermic as indicated by a positive heat of formation, ΔH°f of 36 kJ/mol. Despite its intrinsic instability, B2H6 is kinetically quite stable and possesses an extensive chemistry.
# Structure and bonding
Diborane adopts a D2h structure containing four terminal and two bridging hydrides. The molecular orbital model indicates that the bonding between boron and the terminal hydrides is fairly conventional, not unlike the bonding between carbon and hydride in ethane. The bonding between the boron atoms and the bridging hydrogen atoms is, however, distinctive relative to ordinary hydrocarbons. Formed two 2-center, 2-electron bonds with the terminal hydrogen atoms, each boron "has" one electron remaining for additional bonding. The bridging hydrogen atoms each provide one electron each. Thus the B2H2 ring is held together with four electrons. The lengths of the B-Hbridge bonds and the B-Hterminal bonds are 1.33 and 1.19 Å, respectively. The difference in the lengths of these bonds reflects the difference in their strengths: the B-Hbridge bonds are relatively weaker. The bonding between the boron atoms and two bridging hydrides of diborane is an example of 3-center-2-electron bonding. The structure is equivalent to that for isoelectronic
# Production and syntheses
Diborane is so central and has been studied so often that many syntheses exist. Most preparations entail reactions of hydride donors with boron halides or alkoxides. The industrial synthesis involves the reduction of BF3:
Two laboratory methods start from boron trichloride with lithium aluminium hydride or from boron trifluoride ether solution with sodium borohydride. Both methods yield in up to 30% of diborane:
Older methods entail the direct reaction of borohydride salts with a non-oxidizing acid, such as sulfuric acid or phosphoric acid.
Similarly, oxidation of borohydride salts has been demonstrated and remains convenient for small scale preparations:
# Reactions
Diborane is a highly reactive and versatile reagent that has a large number of applications. Its dominating reaction pattern involves formation of adducts with Lewis bases. Often such initial adducts proceed rapidly to give other products. It reacts with ammonia to form borazine. Diborane also reacts readily with alkynes to form substituted alkene products which will readily undergo further addition reactions.
Diborane reacts with water to form hydrogen and boric acid.
The compound forms complexes with Lewis bases. Notable are the complexes with THF and dimethyl sulfide, both liquid compounds are popular reducing agents in organic chemistry. In these 1:1 complexes, boron assumes a tetrahedral geometry, being bound to three hydrides and the Lewis base (THF or Me2S). The THF adduct is usually prepared as a 1:5 solution in THF. The latter is indefinitely stable when stored under nitrogen at room temperature.
# Reagent in organic synthesis
Diborane is the central organic synthesis reagent for hydroboration, whereby alkenes add across the B-H bonds to give trialkylboranes:
This reaction is regioselective, and the product trialkylboranes can be converted to useful organic derivatives. With bulky alkenes one can prepare species such as 2, which are also useful reagents in more specialized applications.
Diborane is used as a reducing agent roughly complementary to the reactivity of lithium aluminium hydride. The compound readily reduces carboxylic acids to the corresponding alcohols, whereas ketones react only sluggishly.
# History
Diborane was first synthesised in the 19th century by hydrolysis of metal borides, but it was never analysed. From 1912 to 1936, the major pioneer in the chemistry of boron hydrides, Alfred Stock, undertook his research that led to the methods for the synthesis and handling of the highly reactive, volatile, and often toxic boron hydrides. He proposed the first ethane like structure of diborane. Electron diffraction from S. H. Bauer appeared to initially supported his proposed structure.
Because of a personal communication with L. Pauling(who supported the ethane-like structure), H. I. Schlessinger did not specifically discuss 3-center-2-electron bonding in his then classic review in the early 1940's. The review does, however, discuss the C2v structure in some depth, "It is to be recognized that this formulation easily accounts for many of the chemical properties of diborane..."
In 1943 an undergraduate student, H. Christopher Longuet-Higgins, in Oxford published the currently accepted structure together with R. P. Bell. This structure had already been described in 1921. The years following the Longuet-Higgins/Bell proposal witnessed a colorful discussion about the correct structure. The debate ended with the electron diffraction measurement in 1951 by K. Hedberg and V. Schomaker, with the confirmation of the structure shown in the schemes on this page.
William Nunn Lipscomb, Jr. further confirmed the molecular structure of boranes using X-ray crystallography in the 1950's, and developed theories to explain its bonding. Later, he applied the same methods to related problems, including the structure of carboranes on which he directed the research of future Nobel Prize winner Roald Hoffmann. Lipscomb received The Nobel Prize in Chemistry in 1976 for his efforts.
# Other uses
Diborane is used in rocket propellants, as a rubber vulcaniser, as a catalyst for hydrocarbon polymerisation, as a flame-speed accelerator, and as a doping agent for the production of semiconductors. It is also an intermediate in the production of highly pure boron for semiconductor production.
# Safety
The toxic effects of diborane are primarily due to its irritant properties. Short-term exposure to diborane can cause a sensation of tightness of the chest, shortness of breath, cough, and wheezing. These signs and symptoms can occur immediately or be delayed for up to 24 hours. Skin and eye irritation can also occur. Studies in animals have shown that diborane causes the same type of effects observed in humans.
People exposed for a long time to low amounts of diborane have experienced respiratory irritation, seizures, fatigue, drowsiness, confusion, and occasional transient tremors. | Diborane
Template:Chembox new
Diborane is the chemical compound with the formula B2H6. It is a colorless gas at room temperature with a repulsively sweet odor. B2H6 mixes well with air, easily forming explosive mixtures. Diborane will ignite spontaneously in moist air at room temperature. Synonyms include boroethane, boron hydride, and diboron hexahydride.
B2H6 is a key boron compound with a variety of applications. The compound is endothermic as indicated by a positive heat of formation, ΔH°f of 36 kJ/mol. Despite its intrinsic instability, B2H6 is kinetically quite stable and possesses an extensive chemistry.
# Structure and bonding
Diborane adopts a D2h structure containing four terminal and two bridging hydrides. The molecular orbital model indicates that the bonding between boron and the terminal hydrides is fairly conventional, not unlike the bonding between carbon and hydride in ethane. The bonding between the boron atoms and the bridging hydrogen atoms is, however, distinctive relative to ordinary hydrocarbons. Formed two 2-center, 2-electron bonds with the terminal hydrogen atoms, each boron "has" one electron remaining for additional bonding. The bridging hydrogen atoms each provide one electron each. Thus the B2H2 ring is held together with four electrons. The lengths of the B-Hbridge bonds and the B-Hterminal bonds are 1.33 and 1.19 Å, respectively. The difference in the lengths of these bonds reflects the difference in their strengths: the B-Hbridge bonds are relatively weaker. The bonding between the boron atoms and two bridging hydrides of diborane is an example of 3-center-2-electron bonding. The structure is equivalent to that for isoelectronic [C2H62+, which would arise from the diprotonation of the planar molecule ethene. B2H6 is one of many compounds with such unusual bonding. This 3-center-2-electron bond is sometimes called a 'banana bond'.[1]
# Production and syntheses
Diborane is so central and has been studied so often that many syntheses exist. Most preparations entail reactions of hydride donors with boron halides or alkoxides. The industrial synthesis involves the reduction of BF3:
Two laboratory methods start from boron trichloride with lithium aluminium hydride or from boron trifluoride ether solution with sodium borohydride. Both methods yield in up to 30% of diborane:
Older methods entail the direct reaction of borohydride salts with a non-oxidizing acid, such as sulfuric acid or phosphoric acid.
Similarly, oxidation of borohydride salts has been demonstrated and remains convenient for small scale preparations:
# Reactions
Diborane is a highly reactive and versatile reagent that has a large number of applications.[2] Its dominating reaction pattern involves formation of adducts with Lewis bases. Often such initial adducts proceed rapidly to give other products. It reacts with ammonia to form borazine. Diborane also reacts readily with alkynes to form substituted alkene products which will readily undergo further addition reactions.
Diborane reacts with water to form hydrogen and boric acid.
The compound forms complexes with Lewis bases. Notable are the complexes with THF and dimethyl sulfide, both liquid compounds are popular reducing agents in organic chemistry. In these 1:1 complexes, boron assumes a tetrahedral geometry, being bound to three hydrides and the Lewis base (THF or Me2S). The THF adduct is usually prepared as a 1:5 solution in THF. The latter is indefinitely stable when stored under nitrogen at room temperature.
# Reagent in organic synthesis
Diborane is the central organic synthesis reagent for hydroboration, whereby alkenes add across the B-H bonds to give trialkylboranes:
This reaction is regioselective, and the product trialkylboranes can be converted to useful organic derivatives. With bulky alkenes one can prepare species such as [HBR2]2, which are also useful reagents in more specialized applications.
Diborane is used as a reducing agent roughly complementary to the reactivity of lithium aluminium hydride. The compound readily reduces carboxylic acids to the corresponding alcohols, whereas ketones react only sluggishly.
# History
Diborane was first synthesised in the 19th century by hydrolysis of metal borides, but it was never analysed. From 1912 to 1936, the major pioneer in the chemistry of boron hydrides, Alfred Stock, undertook his research that led to the methods for the synthesis and handling of the highly reactive, volatile, and often toxic boron hydrides. He proposed the first ethane like structure of diborane.[3] Electron diffraction from S. H. Bauer appeared to initially supported his proposed structure.[4][5]
Because of a personal communication with L. Pauling(who supported the ethane-like structure), H. I. Schlessinger did not specifically discuss 3-center-2-electron bonding in his then classic review in the early 1940's.[6] The review does, however, discuss the C2v structure in some depth, "It is to be recognized that this formulation easily accounts for many of the chemical properties of diborane..."
In 1943 an undergraduate student, H. Christopher Longuet-Higgins, in Oxford published the currently accepted structure together with R. P. Bell.[7] This structure had already been described in 1921.[8][9][10] The years following the Longuet-Higgins/Bell proposal witnessed a colorful discussion about the correct structure. The debate ended with the electron diffraction measurement in 1951 by K. Hedberg and V. Schomaker, with the confirmation of the structure shown in the schemes on this page.[11]
William Nunn Lipscomb, Jr. further confirmed the molecular structure of boranes using X-ray crystallography in the 1950's, and developed theories to explain its bonding. Later, he applied the same methods to related problems, including the structure of carboranes on which he directed the research of future Nobel Prize winner Roald Hoffmann. Lipscomb received The Nobel Prize in Chemistry in 1976 for his efforts.
# Other uses
Diborane is used in rocket propellants, as a rubber vulcaniser, as a catalyst for hydrocarbon polymerisation, as a flame-speed accelerator, and as a doping agent for the production of semiconductors. It is also an intermediate in the production of highly pure boron for semiconductor production.
# Safety
The toxic effects of diborane are primarily due to its irritant properties. Short-term exposure to diborane can cause a sensation of tightness of the chest, shortness of breath, cough, and wheezing. These signs and symptoms can occur immediately or be delayed for up to 24 hours. Skin and eye irritation can also occur. Studies in animals have shown that diborane causes the same type of effects observed in humans.
People exposed for a long time to low amounts of diborane have experienced respiratory irritation, seizures, fatigue, drowsiness, confusion, and occasional transient tremors. | https://www.wikidoc.org/index.php/Diborane | |
80291c688a5b71707c2f2696f094e96d320173d5 | wikidoc | Didymium | Didymium
Didymium (Greek: twin element) is a mixture of the elements praseodymium and neodymium. It is used in safety glasses for glassblowing and blacksmithing, especially when a gas (propane) powered forge is used, where it provides a filter which blocks the yellowish light emitted by the hot sodium in the glass, without having a detrimental effect on general vision, unlike dark welder's glasses. Blocked also, is the strong ultraviolet light emitted by the superheated forge gases and insulation lining the forge walls thereby saving the crafters' eyes from serious cumulative damage. (See also arc eye, also known as welder's flash or photokeratitis.)
Didymium photographic filters are often used to enhance fall scenery by making leaves appear more vibrant. This is accomplished via the special properties of the substance which causes the removal of part of the orange region of the color spectrum. When present, this group of colors tends to make certain elements of a picture appear "muddy".
Didymium is also used in calibration materials.
# History
Didymium was discovered by Carl Mosander in 1841 and was so named because it is very similar to lanthanum, with which it was found. Mosander wrongly believed didymium to be an element, under the impression that "ceria" (sometimes called cerite) isolated by Jöns Jakob Berzelius in 1803 was really a mixture of cerium, lanthanum and didymium. He was right about lanthanum's being an element, but not about didymium. Mosander did as well as could be expected at the time, since spectroscopy had not yet been invented. His three "elements" accounted for at least 95% of the rare earths in the original cerite from Bastnäs, Sweden. Mosander may have named "didymium" with a bit of tongue-in-cheek: an allusion to the fact that his four children had been born as pairs of twins! Didymium had not been difficult to find, since it was providing the pinkish tinge to the salts of 1803 ceria when in trivalent form. The real tour de force was to find the colorless lanthanum in the mixture! During the period when didymium was believed to be an element, the symbol Di was used for it.
In 1874 Per Teodor Cleve concluded that didymium was composed from two elements.In 1885 Carl Auer von Welsbach succeeded in separating salts of these elements, today known as praseodymium and neodymium, by a fractional crystallization of the double ammonium nitrates from nitric acid. He wanted to name his two elements "praseodidymium" and "neodidymium" ("green didymium" and "new didymium", respectively), but a syllable was soon dropped from each. The "didymium" name lived on in untruncated version, in part due to the use in glassblower's goggles.
During World War I, didymium glass was reputedly used to send Morse Code across the battlefields. Didymium did not absorb enough light to make the variation in lamp intensity obvious, but anyone with binoculars attached to a prism could see the absorption bands flash on or off.
The name lived on also in the rare earth industry. In the USA, commercial "didymium" salts were what remained after cerium was removed from the natural abundance mixture obtained from monazite, and thus contained lanthanum as well as Mosander's "didymium". A typical composition might have been 46% La, 34% Nd, 11% Pr, remainder mostly Sm and Gd, for material extracted from South African "rock" monazite (from Steenkampskraal). European usage was closer to the Mosander composition. Such cerium-depleted light lanthanide mixtures have been widely used to make petroleum-cracking catalysts. The actual ratio of praseodymium to neodymium varies somewhat depending on the source, but is often around 1:3. Neodymium always dominates, which is why it got the "neo" appellation, being responsible for most of the color of the old "element" in its salts. Typically, in ores, neodymium is higher in relative abundance in monazite, as compared to the bastnaesite compositions, and the difference is noticeable when unseparated mixtures derived from each are examined side-by-side: the monazite-derived products are more pinkish, and the bastnaesite-derived products are more brownish in tinge, due to the latter's increased relative praseodymium content. (The original cerite from Bastnaes has a rare earth composition highly similar to that of monazite sand.)
In the late 1920s, Leo Moser recombined praseodymium and neodymium in a 1:1 ratio to create his "Heliolite" glass, which has color-changing properties between amber, reddish, and green depending on the light source.
Recently, it was found that praseodymium could be included in the neodymium-iron-boron magnet composition without excessive sacrifice in magnetic strength. This has the effect of "stretching" the neodymium supply, while simultaneously finding a home for the under-utilized praseodymium. For such magnets, the appropriate mixture can be prepared directly by solvent extraction without purifying either component separately.
de:Didym | Didymium
Didymium (Greek: twin element) is a mixture of the elements praseodymium and neodymium. It is used in safety glasses for glassblowing and blacksmithing, especially when a gas (propane) powered forge is used, where it provides a filter which blocks the yellowish light emitted by the hot sodium in the glass, without having a detrimental effect on general vision, unlike dark welder's glasses. Blocked also, is the strong ultraviolet light emitted by the superheated forge gases and insulation lining the forge walls thereby saving the crafters' eyes from serious cumulative damage. (See also arc eye, also known as welder's flash or photokeratitis.)
Didymium photographic filters are often used to enhance fall scenery by making leaves appear more vibrant. This is accomplished via the special properties of the substance which causes the removal of part of the orange region of the color spectrum. When present, this group of colors tends to make certain elements of a picture appear "muddy".
Didymium is also used in calibration materials.
# History
Didymium was discovered by Carl Mosander in 1841 and was so named because it is very similar to lanthanum, with which it was found. Mosander wrongly believed didymium to be an element, under the impression that "ceria" (sometimes called cerite) isolated by Jöns Jakob Berzelius in 1803 was really a mixture of cerium, lanthanum and didymium. He was right about lanthanum's being an element, but not about didymium. Mosander did as well as could be expected at the time, since spectroscopy had not yet been invented. His three "elements" accounted for at least 95% of the rare earths in the original cerite from Bastnäs, Sweden. Mosander may have named "didymium" with a bit of tongue-in-cheek: an allusion to the fact that his four children had been born as pairs of twins![citation needed] Didymium had not been difficult to find, since it was providing the pinkish tinge to the salts of 1803 ceria when in trivalent form. The real tour de force was to find the colorless lanthanum in the mixture! During the period when didymium was believed to be an element, the symbol Di was used for it.
In 1874 Per Teodor Cleve concluded that didymium was composed from two elements.In 1885 Carl Auer von Welsbach succeeded in separating salts of these elements, today known as praseodymium and neodymium, by a fractional crystallization of the double ammonium nitrates from nitric acid. He wanted to name his two elements "praseodidymium" and "neodidymium" ("green didymium" and "new didymium", respectively), but a syllable was soon dropped from each. The "didymium" name lived on in untruncated version, in part due to the use in glassblower's goggles.
During World War I, didymium glass was reputedly used to send Morse Code across the battlefields. Didymium did not absorb enough light to make the variation in lamp intensity obvious, but anyone with binoculars attached to a prism could see the absorption bands flash on or off.
The name lived on also in the rare earth industry. In the USA, commercial "didymium" salts were what remained after cerium was removed from the natural abundance mixture obtained from monazite, and thus contained lanthanum as well as Mosander's "didymium". A typical composition might have been 46% La, 34% Nd, 11% Pr, remainder mostly Sm and Gd, for material extracted from South African "rock" monazite (from Steenkampskraal). European usage was closer to the Mosander composition. Such cerium-depleted light lanthanide mixtures have been widely used to make petroleum-cracking catalysts. The actual ratio of praseodymium to neodymium varies somewhat depending on the source, but is often around 1:3. Neodymium always dominates, which is why it got the "neo" appellation, being responsible for most of the color of the old "element" in its salts. Typically, in ores, neodymium is higher in relative abundance in monazite, as compared to the bastnaesite compositions, and the difference is noticeable when unseparated mixtures derived from each are examined side-by-side: the monazite-derived products are more pinkish, and the bastnaesite-derived products are more brownish in tinge, due to the latter's increased relative praseodymium content. (The original cerite from Bastnaes has a rare earth composition highly similar to that of monazite sand.)
In the late 1920s, Leo Moser recombined praseodymium and neodymium in a 1:1 ratio to create his "Heliolite" glass, which has color-changing properties between amber, reddish, and green depending on the light source. [One can only hope that an appropriate intermediate fraction of the Pr-Nd separation might have been used, to save some expense, since at the time, separated praseodymium and neodymium oxides were the most costly glass colorants in use.]
Recently, it was found that praseodymium could be included in the neodymium-iron-boron magnet composition without excessive sacrifice in magnetic strength. This has the effect of "stretching" the neodymium supply, while simultaneously finding a home for the under-utilized praseodymium. For such magnets, the appropriate mixture can be prepared directly by solvent extraction without purifying either component separately.
de:Didym
Template:WS | https://www.wikidoc.org/index.php/Didymium | |
09d0c3e9c242d10dff6350d8893590d4c5f3f102 | wikidoc | Differin | Differin
Differin is a trade name for a medication for acne vulgaris made by Galderma Laboratories. Its active ingredient is adapalene.
It is available in a 45g tube under the NDC 0299-5910-45 in the United States, as well as a 35g tube in Australia. It is available in either a gel or creme form. Both forms contain 0.1% adapalene, a retinoid-like compound, as the active ingredient.
Differin works by modulating skin cell differentiation and growth and therefore regulating oil production and reducing acne over a long period of time. It has both exfoliating and anti-inflammatory effects. Studies show it is most effective on noninflammatory acne.
This drug will give much better results if a benzoyl peroxide wash is used morning and night and benzoyl peroxide lotion is applied in the a.m only along with the differin used in the p.m. However, unlike Retin-A, adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure. | Differin
Differin is a trade name for a medication for acne vulgaris made by Galderma Laboratories. Its active ingredient is adapalene.
It is available in a 45g tube under the NDC 0299-5910-45 in the United States, as well as a 35g tube in Australia. It is available in either a gel or creme form. Both forms contain 0.1% adapalene, a retinoid-like compound, as the active ingredient.
Differin works by modulating skin cell differentiation and growth and therefore regulating oil production and reducing acne over a long period of time. It has both exfoliating and anti-inflammatory effects. Studies show it is most effective on noninflammatory acne.
This drug will give much better results if a benzoyl peroxide wash is used morning and night and benzoyl peroxide lotion is applied in the a.m only along with the differin used in the p.m. However, unlike Retin-A, adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure. | https://www.wikidoc.org/index.php/Differin | |
b0fec6263bf9412d5f76f054e01d263f1ef9690b | wikidoc | Diketone | Diketone
A diketone is a molecule containing two ketone groups. The simpliest diketone is diacetyl, also known as 2,3-butanedione. 2,3-Butanedione, acetylacetone, and hexane-2,5-dione are examples of 1,2-, 1,3-, and 1,4-diketones, respectively. Dimedone (5,5-dimethyl-1,3-cyclohexanedione, CAS registry number 126-81-8), is an example of a cyclic diketone.
# Reactions
1,3-Diketones, such as acetylacetone, are particularly prone to form stable enols or enolates because of conjugation of the enol or enolate with the other carbonyl group, and the stability gained in forming a six-membered ring, (hydrogen bonded in the case of the enol or containing the counter ion in the case of the enolate).
Scheme 1. Tautomerism of 2,4-pentanedione
The conjugate base derived from 1,3-ketones form complexes with metal ions.
Diketones with one or two methylene groups separating the carbonyl groups typically coexist with their enol tautomers. The reactions of such dicarbonyls are very similar to those of simple ketones.
# EU Regulation
The EU Commission has declared that diketones (for example acetylacetone, CH3COCH2COCH3) are like dialcohols and hydroxyketones in that they are in vitro and in vivo genotoxic chemical substances and therefore have been forbidden as nutrition additives since 2005.
As Diacetyl is a diketone (in fact the simplist) it may be eventually subject to this EU regulation. | Diketone
Template:Cleanup
A diketone is a molecule containing two ketone groups. The simpliest diketone is diacetyl, also known as 2,3-butanedione. 2,3-Butanedione, acetylacetone, and hexane-2,5-dione are examples of 1,2-, 1,3-, and 1,4-diketones, respectively. Dimedone (5,5-dimethyl-1,3-cyclohexanedione, CAS registry number 126-81-8), is an example of a cyclic diketone.
# Reactions
1,3-Diketones, such as acetylacetone, are particularly prone to form stable enols or enolates because of conjugation of the enol or enolate with the other carbonyl group, and the stability gained in forming a six-membered ring, (hydrogen bonded in the case of the enol or containing the counter ion in the case of the enolate).
Scheme 1. Tautomerism of 2,4-pentanedione
The conjugate base derived from 1,3-ketones form complexes with metal ions.
Diketones with one or two methylene groups separating the carbonyl groups typically coexist with their enol tautomers. The reactions of such dicarbonyls are very similar to those of simple ketones.
# EU Regulation
The EU Commission has declared that diketones (for example acetylacetone, CH3COCH2COCH3) are like dialcohols and hydroxyketones in that they are in vitro and in vivo genotoxic chemical substances and therefore have been forbidden as nutrition additives since 2005.[1]
As Diacetyl is a diketone (in fact the simplist) it may be eventually subject to this EU regulation. | https://www.wikidoc.org/index.php/Diketone | |
aaa7c4e75e1a2a8737851890e22331027629f642 | wikidoc | Dill oil | Dill oil
Dill oil is the oil extracted from the seeds or leaves/stems (dillweed) of the Dill plant. It can be used with water to create Dill Water
# Origin
Also known as Indian Dill, originally from Southwest Asia, Dill is an annual or biennial herb that grows up to 1 meter (3 feet). It has green feathery leaves and umbels of small yellow flowers, followed by tiny compressed seeds.
It was popular with the Egyptians, Greeks and Romans, who called it "Anethon" from which the botanical name was derived. The common name comes from the Anglo-Saxon dylle or dylla, which then changed to dill. The word means 'to lull' - referring to its soothing properties. In the Middle Ages it was used as a charm against witchcraft.
From 1812 onwards, when Charlemagne, Emperor of France, ordered the extensive cultivation of this herb, it has been widely used, especially as a culinary herb.
# Oil properties
Dill oil is known for its grass-like smell and its pale yellow color, with a watery viscosity.
# Uses
- Gripe water is often made of the fresh herb and given to babies and children for colic, or other digestive disorders, but dill oil is not used for this purpose, as it is too strong.
- Dill oil has been known to help to overcome the feeling of being overwhelmed and is also helpful for digestive problems in adults, easing flatulence, constipation and hiccups.
- Believed to ease the mind, calm headaches and help with excess sweating due to nervous tension. It can also stimulate milk flow in nursing mothers and promotes the healing of wounds.
# Dill Oil Extraction
Dill oil is extracted by steam distillation, mainly from the seeds, or the whole herb, fresh or partly dried. | Dill oil
Dill oil is the oil extracted from the seeds or leaves/stems (dillweed) of the Dill plant. It can be used with water to create Dill Water
# Origin
Also known as Indian Dill, originally from Southwest Asia, Dill is an annual or biennial herb that grows up to 1 meter (3 feet). It has green feathery leaves and umbels of small yellow flowers, followed by tiny compressed seeds.
It was popular with the Egyptians, Greeks and Romans, who called it "Anethon" from which the botanical name was derived. The common name comes from the Anglo-Saxon dylle or dylla, which then changed to dill. The word means 'to lull' - referring to its soothing properties. In the Middle Ages it was used as a charm against witchcraft.
From 1812 onwards, when Charlemagne, Emperor of France, ordered the extensive cultivation of this herb, it has been widely used, especially as a culinary herb.
# Oil properties
Dill oil is known for its grass-like smell and its pale yellow color, with a watery viscosity.
# Uses
- Gripe water is often made of the fresh herb and given to babies and children for colic, or other digestive disorders, but dill oil is not used for this purpose, as it is too strong.
- Dill oil has been known to help to overcome the feeling of being overwhelmed and is also helpful for digestive problems in adults, easing flatulence, constipation and hiccups.
- Believed to ease the mind, calm headaches and help with excess sweating due to nervous tension. It can also stimulate milk flow in nursing mothers and promotes the healing of wounds.
# Dill Oil Extraction
Dill oil is extracted by steam distillation, mainly from the seeds, or the whole herb, fresh or partly dried. | https://www.wikidoc.org/index.php/Dill_oil | |
4855b165b6df59d444fb158dea8ddb6a17efa054 | wikidoc | Dilution | Dilution
Dilution may refer to:
- Reducing the concentration of a chemical
- Serial dilution, a common way of going about this reduction of concentration.
- Homeopathic dilution In homeopathic potencies of over 12C (24X), no molecules of the original substance remain.
- Dilution (equation), an equation to calculate the rate a gas dilutes
- Dilution gene, a gene that lightens the coat color of certain living things
- Phrase used in indicator dilution theory
- Phrase used in dilution space of substances
nl:Verdunning | Dilution
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Dilution may refer to:
- Reducing the concentration of a chemical
- Serial dilution, a common way of going about this reduction of concentration.
- Homeopathic dilution In homeopathic potencies of over 12C (24X), no molecules of the original substance remain.
- Dilution (equation), an equation to calculate the rate a gas dilutes
- Dilution gene, a gene that lightens the coat color of certain living things
- Phrase used in indicator dilution theory
- Phrase used in dilution space of substances
Template:Disambig
nl:Verdunning
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Dilution | |
2568c411cbb01c334b89e24d43b95304eb7e7052 | wikidoc | Nitrogen | Nitrogen
Nitrogen (Template:PronEng) is a chemical element which has the symbol N and atomic number 7. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78.1% by volume of Earth's atmosphere. Nitrogen is a constituent element of amino acids and therefore of all living organisms. Many industrially important compounds, such as ammonia, nitric acid, and cyanides, contain nitrogen.
# Properties
Nitrogen is a nonmetal, with an electronegativity of 3.0. It has five electrons in its outer shell and is therefore trivalent in most compounds. The triple bond in molecular nitrogen (N2) is one of the strongest in nature. The resulting difficulty of converting (N2) into other compounds, and the ease (and associated high energy release) of converting nitrogen compounds into elemental N2, have dominated the role of nitrogen in both nature and human economic activities.
At atmospheric pressure molecular nitrogen condenses (liquifies) at 77 K (−195.8 °C) and freezes at 63 K (−210.0 °C) into the beta hexagonal close-packed crystal allotropic form. Below 35.4 K (−237.6 °C) nitrogen assumes the alpha cubic crystal allotropic form. Liquid nitrogen, a fluid resembling water, but with 80.8% of the density, is a common cryogen.
Unstable allotropes of nitrogen consisting of more than two nitrogen atoms have been produced in the laboratory, like N3 and N4. Under extremely high pressures (1.1 million atm) and high temperatures (2000 K), as produced under diamond anvil conditions, nitrogen polymerizes into the single bonded diamond crystal structure, an allotrope nicknamed "nitrogen diamond."
# Occurrence
Nitrogen is the largest single constituent of the Earth's atmosphere (78.082% by volume of dry air, 75.3% by weight in dry air). It is created by fusion processes in stars, and is estimated to be the 7th most abundant chemical element by mass in the universe.
Nitrogen is present in all living organisms in proteins, nucleic acids and other molecules. It is a large component of animal waste (for example, guano), usually in the form of urea, uric acid, ammonium compounds and derivatives of these nitrogenous products, which are essential nutrients for all plants that are unable to fix atmospheric nitrogen.
# Isotopes
There are two stable isotopes of nitrogen: 14N and 15N. By far the most common is 14N (99.634%), which is produced in the CNO cycle in stars and the remaining is 15N. Of the ten isotopes produced synthetically, 13N has a half life of ten minutes and the remaining isotopes have half lives on the order of seconds or less.
Biologically-mediated reactions (e.g., assimilation, nitrification, and denitrification) strongly control nitrogen dynamics in the soil. These reactions typically result in 15N enrichment of the substrate and depletion of the product.
0.73% of the molecular nitrogen in Earth's atmosphere is comprised of the isotopologue 14N15N and almost all the rest is 14N2.
# Electromagnetic spectrum
Molecular nitrogen (14N2) is largely transparent to infrared and visible radiation because it is a homonuclear molecule and thus has no dipole moment to couple to electromagnetic radiation at these wavelengths. Significant absorption occurs at extreme ultraviolet wavelengths, beginning around 100 nanometers. This is associated with electronic transitions in the molecule to states in which charge is not distributed evenly between nitrogen atoms. Nitrogen absorption leads to significant absorption of ultraviolet radiation in the Earth's upper atmosphere as well as in the atmospheres of other planetary bodies. For similar reasons, pure molecular nitrogen lasers typically emit light in the ultraviolet range.
Nitrogen also makes a contribution to visible air glow from the Earth's upper atmosphere, through electron impact excitation followed by emission. This visible blue air glow (seen in the polar aurora and in the re-entry glow of returning spacecraft) typically results not from molecular nitrogen, but rather from free nitrogen atoms combining with oxygen to form nitric oxide (NO).
# Applications
## Liquid nitrogen
Liquid nitrogen is a cryogenic liquid. At atmospheric pressure, it boils at −196.5 °C. When insulated in proper containers such as dewar flasks, it can be transported without much evaporative losses.
Like dry ice, the main use of liquid nitrogen is as a refrigerant. Among other things, it is used in the cryopreservation of blood, reproductive cells (sperm and egg), and other biological samples and materials. It is also used in cold traps for certain laboratory equipment. It has also been used to cool central processing units and other devices in computers which are overclocked, and which produce more heat than during normal operation.
# Biological role
Nitrogen is an essential part of amino acids and nucleic acids, both of which are essential to all life on Earth.
Specific bacteria (e.g. Rhizobium trifolium) possess nitrogenase enzymes which can fix atmospheric nitrogen (see nitrogen fixation) into a form (ammonium ion) which is chemically useful to higher organisms. This process requires a large amount of energy and anoxic conditions. Such bacteria may be free in the soil (e.g. Azotobacter) but normally exist in a symbiotic relationship in the root nodules of leguminous plants (e.g. clover, Trifolium species, or the soy bean plant, Glycine max). Nitrogen-fixing bacteria can be symbiotic with a number of unrelated plant species. Common examples are legumes, alders (Alnus) spp., lichens, Casuarina, Myrica, liverworts, and Gunnera.
As part of the symbiotic relationship, the plant subsequently converts the ammonium ion to nitrogen oxides and amino acids to form proteins and other biologically useful molecules, such as alkaloids. In return for the usable (fixed) nitrogen, the plant secretes sugars to the symbiotic bacteria.
Nitrogen compounds are basic building blocks in animal biology. Animals use nitrogen-containing amino acids from plant sources, as starting materials for all nitrogen-compound animal biochemistry, including the manufacture of proteins and nucleic acids. Some plant-feeding insects are so dependent on nitrogen in their diet, that varying the amount of nitrogen fertilizer applied to a plant can affect the rate of reproduction of the insects feeding on it.
Animal metabolism of NO results in production of nitrite. Animal metabolism of nitrogen in proteins generally results in excretion of urea, while animal metabolism of nucleic acids results in excretion of urea and uric acid. The characteristic odor of animal flesh decay is caused by nitrogen-containing long-chain amines, such as putrescine and cadaverine.
Decay of organisms and their waste products may produce small amounts of nitrate, but most decay eventually returns nitrogen content to the atmosphere, as molecular nitrogen.
# Nitrogen compounds in industry
## Simple compounds
See also the category Nitrogen compounds.
The main neutral hydride of nitrogen is ammonia (NH3), although hydrazine (N2H4) is also commonly used. Ammonia is more basic than water by 6 orders of magnitude. In solution ammonia forms the ammonium ion (NH4+). Liquid ammonia (b.p. 240 K) is amphiprotic (displaying either Brønsted-Lowry acidic or basic character) and forms ammonium and the less common amide ions (NH2-); both amides and nitride (N3-) salts are known, but decompose in water. Singly, doubly, triply and quadruply substituted alkyl compounds of ammonia are called amines (four substitutions, to form commercially and biologically important quarternary amines, results in a positively charged nitrogen, and thus a water-soluble, or at least amphiphilic, compound). Larger chains, rings and structures of nitrogen hydrides are also known, but are generally unstable. N22+ is another polyatomic cation as in hydrazine.
Other classes of nitrogen anions (negatively charged ions) are the poisonous azides (N3-), which are linear and isoelectronic to carbon dioxide, but which bind to important iron-containing enzymes in the body in a manner more resembling cyanide. Another molecule of the same structure is the colorless and relatively inert anesthetic gas dinitrogen monoxide (N2O), also known as laughing gas. This is one of a variety of oxides, the most prominent of which are nitrogen monoxide (NO) (known more commonly as nitric oxide in biology), a natural free radical molecule used by the body as a signal for short-term control of smooth muscle in the circulation. Another notable nitrogen oxide compound (a family often abbreviated NOx) is the reddish and poisonous nitrogen dioxide (NO2), which also contains an unpaired electron and is an important component of smog. Nitrogen molecules containing unpaired electrons show an understandable tendency to dimerize (thus pairing the electrons), and are generally highly reactive.
The more standard oxides, dinitrogen trioxide (N2O3) and dinitrogen pentoxide (N2O5), are actually fairly unstable and explosive-- a tendency which is driven by the stability of N2 as a product. The corresponding acids are nitrous (HNO2) and nitric acid (HNO3), with the corresponding salts called nitrites and nitrates. Nitric acid is one of the few acids stronger than hydronium, and is a fairly strong oxidizing agent.
Nitrogen can also be found in organic compounds. Common nitrogen functional groups include: amines, amides, nitro groups, imines, and enamines. The amount of nitrogen in a chemical substance can be determined by the Kjeldahl method.
## Nitrogen compounds of notable economic importance
Nitrogen is a constituent of molecules in every major drug class in pharmacology and medicine. Nitrous oxide (N2O) was discovered early in the 19th century to be a partial anesthetic, though it was not used as a surgical anesthetic until later. Called "laughing gas", it was found capable of inducing a state of social disinhibition resembling drunkenness. Other notable nitrogen-containing drugs are drugs derived from plant alkaloids, such as morphine (there exist many alkaloids known to have pharmacological effects; in some cases they appear natural chemical defences of plants against predation). Nitrogen containing drugs include all of the major classes of antibiotics, and organic nitrate drugs like nitroglycerin and nitroprusside which regulate blood pressure and heart action by mimicking the action of nitric oxide.
# Dangers
Rapid release of nitrogen gas into an enclosed space can displace oxygen, and therefore represents an asphyxiation hazard. This may happen with few warning symptoms, since the human carotid body is a relatively slow and a poor low-oxygen (hypoxia) sensing system. An example occurred shortly before the launch of the first Space Shuttle mission in 1981, when two technicians lost consciousness and died after they walked into a space located in the Shuttle's Mobile Launcher Platform that was pressurized with pure nitrogen as a precaution against fire. The technicians would have been able to exit the room if they had experienced early symptoms from nitrogen-breathing.
When inhaled at high partial pressures (more than about 3 atmospheres, encountered at depths below about 30 m in scuba diving) nitrogen begins to act as an anesthetic agent. It can cause nitrogen narcosis, a temporary semi-anesthetized state of mental impairment similar to that caused by nitrous oxide.
Nitrogen also dissolves in the bloodstream and body fats, and rapid decompression (particularly in the case of divers ascending too quickly, or astronauts decompressing too quickly from cabin pressure to spacesuit pressure) can lead to a potentially fatal condition called decompression sickness (formerly known as caisson sickness or more commonly, the "bends"), when nitrogen bubbles form in the bloodstream, nerves, joints, and other sensitive or vital areas.
Direct skin contact with liquid nitrogen causes severe frostbite (cryogenic burns) within seconds, though not instantly on contact, depending on form of liquid nitrogen (liquid vs. mist) and surface area of the nitrogen-soaked material (soaked clothing or cotton causing more rapid damage than a spill of direct liquid to skin, which for a few seconds is protected by the Leidenfrost effect). | Nitrogen
Template:Infobox nitrogen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Nitrogen (Template:PronEng) is a chemical element which has the symbol N and atomic number 7. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78.1% by volume of Earth's atmosphere. Nitrogen is a constituent element of amino acids and therefore of all living organisms. Many industrially important compounds, such as ammonia, nitric acid, and cyanides, contain nitrogen.
# Properties
Nitrogen is a nonmetal, with an electronegativity of 3.0. It has five electrons in its outer shell and is therefore trivalent in most compounds. The triple bond in molecular nitrogen (N2) is one of the strongest in nature. The resulting difficulty of converting (N2) into other compounds, and the ease (and associated high energy release) of converting nitrogen compounds into elemental N2, have dominated the role of nitrogen in both nature and human economic activities.
At atmospheric pressure molecular nitrogen condenses (liquifies) at 77 K (−195.8 °C) and freezes at 63 K (−210.0 °C) into the beta hexagonal close-packed crystal allotropic form. Below 35.4 K (−237.6 °C) nitrogen assumes the alpha cubic crystal allotropic form. Liquid nitrogen, a fluid resembling water, but with 80.8% of the density, is a common cryogen.
Unstable allotropes of nitrogen consisting of more than two nitrogen atoms have been produced in the laboratory, like N3 and N4.[1] Under extremely high pressures (1.1 million atm) and high temperatures (2000 K), as produced under diamond anvil conditions, nitrogen polymerizes into the single bonded diamond crystal structure, an allotrope nicknamed "nitrogen diamond."[2]
# Occurrence
Nitrogen is the largest single constituent of the Earth's atmosphere (78.082% by volume of dry air, 75.3% by weight in dry air). It is created by fusion processes in stars, and is estimated to be the 7th most abundant chemical element by mass in the universe.
Nitrogen is present in all living organisms in proteins, nucleic acids and other molecules. It is a large component of animal waste (for example, guano), usually in the form of urea, uric acid, ammonium compounds and derivatives of these nitrogenous products, which are essential nutrients for all plants that are unable to fix atmospheric nitrogen.
Template:Seealso
# Isotopes
There are two stable isotopes of nitrogen: 14N and 15N. By far the most common is 14N (99.634%), which is produced in the CNO cycle in stars and the remaining is 15N. Of the ten isotopes produced synthetically, 13N has a half life of ten minutes and the remaining isotopes have half lives on the order of seconds or less.
Biologically-mediated reactions (e.g., assimilation, nitrification, and denitrification) strongly control nitrogen dynamics in the soil. These reactions typically result in 15N enrichment of the substrate and depletion of the product.
0.73% of the molecular nitrogen in Earth's atmosphere is comprised of the isotopologue 14N15N and almost all the rest is 14N2.
# Electromagnetic spectrum
Molecular nitrogen (14N2) is largely transparent to infrared and visible radiation because it is a homonuclear molecule and thus has no dipole moment to couple to electromagnetic radiation at these wavelengths. Significant absorption occurs at extreme ultraviolet wavelengths, beginning around 100 nanometers. This is associated with electronic transitions in the molecule to states in which charge is not distributed evenly between nitrogen atoms. Nitrogen absorption leads to significant absorption of ultraviolet radiation in the Earth's upper atmosphere as well as in the atmospheres of other planetary bodies. For similar reasons, pure molecular nitrogen lasers typically emit light in the ultraviolet range.
Nitrogen also makes a contribution to visible air glow from the Earth's upper atmosphere, through electron impact excitation followed by emission. This visible blue air glow (seen in the polar aurora and in the re-entry glow of returning spacecraft) typically results not from molecular nitrogen, but rather from free nitrogen atoms combining with oxygen to form nitric oxide (NO).
# Applications
## Liquid nitrogen
Liquid nitrogen is a cryogenic liquid. At atmospheric pressure, it boils at −196.5 °C. When insulated in proper containers such as dewar flasks, it can be transported without much evaporative losses.
Like dry ice, the main use of liquid nitrogen is as a refrigerant. Among other things, it is used in the cryopreservation of blood, reproductive cells (sperm and egg), and other biological samples and materials. It is also used in cold traps for certain laboratory equipment. It has also been used to cool central processing units and other devices in computers which are overclocked, and which produce more heat than during normal operation.
# Biological role
Nitrogen is an essential part of amino acids and nucleic acids, both of which are essential to all life on Earth.
Specific bacteria (e.g. Rhizobium trifolium) possess nitrogenase enzymes which can fix atmospheric nitrogen (see nitrogen fixation) into a form (ammonium ion) which is chemically useful to higher organisms. This process requires a large amount of energy and anoxic conditions. Such bacteria may be free in the soil (e.g. Azotobacter) but normally exist in a symbiotic relationship in the root nodules of leguminous plants (e.g. clover, Trifolium species, or the soy bean plant, Glycine max). Nitrogen-fixing bacteria can be symbiotic with a number of unrelated plant species. Common examples are legumes, alders (Alnus) spp., lichens, Casuarina, Myrica, liverworts, and Gunnera.
As part of the symbiotic relationship, the plant subsequently converts the ammonium ion to nitrogen oxides and amino acids to form proteins and other biologically useful molecules, such as alkaloids. In return for the usable (fixed) nitrogen, the plant secretes sugars to the symbiotic bacteria.
Nitrogen compounds are basic building blocks in animal biology. Animals use nitrogen-containing amino acids from plant sources, as starting materials for all nitrogen-compound animal biochemistry, including the manufacture of proteins and nucleic acids. Some plant-feeding insects are so dependent on nitrogen in their diet, that varying the amount of nitrogen fertilizer applied to a plant can affect the rate of reproduction of the insects feeding on it.[3]
Animal metabolism of NO results in production of nitrite. Animal metabolism of nitrogen in proteins generally results in excretion of urea, while animal metabolism of nucleic acids results in excretion of urea and uric acid. The characteristic odor of animal flesh decay is caused by nitrogen-containing long-chain amines, such as putrescine and cadaverine.
Decay of organisms and their waste products may produce small amounts of nitrate, but most decay eventually returns nitrogen content to the atmosphere, as molecular nitrogen.
# Nitrogen compounds in industry
## Simple compounds
See also the category Nitrogen compounds.
The main neutral hydride of nitrogen is ammonia (NH3), although hydrazine (N2H4) is also commonly used. Ammonia is more basic than water by 6 orders of magnitude. In solution ammonia forms the ammonium ion (NH4+). Liquid ammonia (b.p. 240 K) is amphiprotic (displaying either Brønsted-Lowry acidic or basic character) and forms ammonium and the less common amide ions (NH2-); both amides and nitride (N3-) salts are known, but decompose in water. Singly, doubly, triply and quadruply substituted alkyl compounds of ammonia are called amines (four substitutions, to form commercially and biologically important quarternary amines, results in a positively charged nitrogen, and thus a water-soluble, or at least amphiphilic, compound). Larger chains, rings and structures of nitrogen hydrides are also known, but are generally unstable. N22+ is another polyatomic cation as in hydrazine.
Other classes of nitrogen anions (negatively charged ions) are the poisonous azides (N3-), which are linear and isoelectronic to carbon dioxide, but which bind to important iron-containing enzymes in the body in a manner more resembling cyanide. Another molecule of the same structure is the colorless and relatively inert anesthetic gas dinitrogen monoxide (N2O), also known as laughing gas. This is one of a variety of oxides, the most prominent of which are nitrogen monoxide (NO) (known more commonly as nitric oxide in biology), a natural free radical molecule used by the body as a signal for short-term control of smooth muscle in the circulation. Another notable nitrogen oxide compound (a family often abbreviated NOx) is the reddish and poisonous nitrogen dioxide (NO2), which also contains an unpaired electron and is an important component of smog. Nitrogen molecules containing unpaired electrons show an understandable tendency to dimerize (thus pairing the electrons), and are generally highly reactive.
The more standard oxides, dinitrogen trioxide (N2O3) and dinitrogen pentoxide (N2O5), are actually fairly unstable and explosive-- a tendency which is driven by the stability of N2 as a product. The corresponding acids are nitrous (HNO2) and nitric acid (HNO3), with the corresponding salts called nitrites and nitrates. Nitric acid is one of the few acids stronger than hydronium, and is a fairly strong oxidizing agent.
Nitrogen can also be found in organic compounds. Common nitrogen functional groups include: amines, amides, nitro groups, imines, and enamines. The amount of nitrogen in a chemical substance can be determined by the Kjeldahl method.
## Nitrogen compounds of notable economic importance
Nitrogen is a constituent of molecules in every major drug class in pharmacology and medicine. Nitrous oxide (N2O) was discovered early in the 19th century to be a partial anesthetic, though it was not used as a surgical anesthetic until later. Called "laughing gas", it was found capable of inducing a state of social disinhibition resembling drunkenness. Other notable nitrogen-containing drugs are drugs derived from plant alkaloids, such as morphine (there exist many alkaloids known to have pharmacological effects; in some cases they appear natural chemical defences of plants against predation). Nitrogen containing drugs include all of the major classes of antibiotics, and organic nitrate drugs like nitroglycerin and nitroprusside which regulate blood pressure and heart action by mimicking the action of nitric oxide.
# Dangers
Rapid release of nitrogen gas into an enclosed space can displace oxygen, and therefore represents an asphyxiation hazard. This may happen with few warning symptoms, since the human carotid body is a relatively slow and a poor low-oxygen (hypoxia) sensing system.[4] An example occurred shortly before the launch of the first Space Shuttle mission in 1981, when two technicians lost consciousness and died after they walked into a space located in the Shuttle's Mobile Launcher Platform that was pressurized with pure nitrogen as a precaution against fire. The technicians would have been able to exit the room if they had experienced early symptoms from nitrogen-breathing.
When inhaled at high partial pressures (more than about 3 atmospheres, encountered at depths below about 30 m in scuba diving) nitrogen begins to act as an anesthetic agent. It can cause nitrogen narcosis, a temporary semi-anesthetized state of mental impairment similar to that caused by nitrous oxide.
Nitrogen also dissolves in the bloodstream and body fats, and rapid decompression (particularly in the case of divers ascending too quickly, or astronauts decompressing too quickly from cabin pressure to spacesuit pressure) can lead to a potentially fatal condition called decompression sickness (formerly known as caisson sickness or more commonly, the "bends"), when nitrogen bubbles form in the bloodstream, nerves, joints, and other sensitive or vital areas.
Direct skin contact with liquid nitrogen causes severe frostbite (cryogenic burns) within seconds, though not instantly on contact, depending on form of liquid nitrogen (liquid vs. mist) and surface area of the nitrogen-soaked material (soaked clothing or cotton causing more rapid damage than a spill of direct liquid to skin, which for a few seconds is protected by the Leidenfrost effect). | https://www.wikidoc.org/index.php/Dinitrogen | |
5da37c869896ef9509e8815d1121f119db002ad3 | wikidoc | Diplegia | Diplegia
Diplegia, when used singularly, refers to paralysis affecting one part of the body and the corresponding part on the other side of the body — usually both legs. It should not be confused with paraplegia, which is a form of paralysis affecting the entire body.
Spastic diplegia is a condition of neuromuscular hypertonia primarily in the muscles of the legs, hips, and pelvis, and is a form of cerebral palsy. Correspondingly, spastic paraplegia refers to hypertonia affecting the entire body.
For example, facial diplegia occurs in 50% of patients with Guillain-Barre Syndrome. | Diplegia
Diplegia, when used singularly, refers to paralysis affecting one part of the body and the corresponding part on the other side of the body — usually both legs. It should not be confused with paraplegia, which is a form of paralysis affecting the entire body.
Spastic diplegia is a condition of neuromuscular hypertonia primarily in the muscles of the legs, hips, and pelvis, and is a form of cerebral palsy. Correspondingly, spastic paraplegia refers to hypertonia affecting the entire body.
For example, facial diplegia occurs in 50% of patients with Guillain-Barre Syndrome. | https://www.wikidoc.org/index.php/Diplegia | |
cd7fc94ad6056d32d768aa1a82c33e123863a415 | wikidoc | Propofol | Propofol
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Propofol is a general anesthetic that is FDA approved for the {{{indicationType}}} of general anesthesia, monitored anesthesia care sedation, sedation for a mechanically ventilated patient, intensive care unit. There is a Black Box Warning for this drug as shown here. Common adverse reactions include dermatologic: injection site pain (up to 28.5% ), gastrointestinal: nausea and vomiting (2% to 2.5% ), musculoskeletal: involuntary movement, muscle (17%).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- General anesthesia: (healthy adults less than 55 years of age) induction, 40 mg IV every 10 seconds until induction onset (2 to 2.5 mg/kg); dose varies for age and surgery type.
- General anesthesia: (healthy adults less than 55 years of age) maintenance, 100 to 200 mcg/kg/min IV infusion (6 to 12 mg/kg/hr); dose varies for age and surgery type.
- General anesthesia: (healthy adults less than 55 years of age) maintenance, 20 to 50 mg increments IV bolus as needed.
- Migraine: 10 mg slow IV push, every 5 to 10 minutes, max 80 mg; mixed with 1 mL lidocaine 2% per 10 mL of propofol 1%; infuse at rate of 1 mL/10 sec.
- Monitored anesthesia care sedation: (healthy adults less than 55 years of age) MAC initiation: 100 to 150 mcg/kg/min (6 to 9 mg/kg/hr) IV infusion or 0.5 mg/kg slow IV injection for 3 to 5 min followed immediately by maintenance infusion.
- Monitored anesthesia care sedation: (healthy adults less than 55 years of age) MAC maintenance: 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/hr) IV infusion or 10 to 20 mg incremental IV bolus doses.
- Procedural sedation: 1 mg/kg IV followed by 0.5 mg/kg every 3 to 5 minutes as needed for sedation.
- Sedation for a mechanically ventilated patient, Intensive care unit: 5 mcg/kg/min (0.3 mg/kg/hr) IV infusion for 5 min then titrate in 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) increments to achieve desired level of sedation; allow minimum of 5 min between dose adjustments; usual maintenance rates 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Propofol in adult patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Propofol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Propofol FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Propofol in pediatric patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Propofol in pediatric patients.
# Contraindications
There is limited information regarding Propofol Contraindications in the drug label.
# Warnings
There is limited information regarding Propofol Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
- Adverse event information is derived from controlled clinical trials and worldwide marketing experience. In the description below, rates of the more common events represent US/Canadian clinical study results. Less frequent events are also derived from publications and marketing experience in over 8 million patients; there are insufficient data to support an accurate estimate of their incidence rates. These studies were conducted using a variety of premedicants, varying lengths of surgical/diagnostic procedures, and various other anesthetic/sedative agents. Most adverse events were mild and transient.
- The following estimates of adverse events for Propofol Injectable Emulsion include data from clinical trials in general anesthesia/MAC sedation (N=2889 adult patients). The adverse events listed below as probably causally related are those events in which the actual incidence rate in patients treated with Propofol Injectable Emulsion was greater than the comparator incidence rate in these trials. Therefore, incidence rates for anesthesia and MAC sedation in adults generally represent estimates of the percentage of clinical trial patients which appeared to have probable causal relationship.
- The adverse experience profile from reports of 150 patients in the MAC sedation clinical trials is similar to the profile established with Propofol Injectable Emulsion during anesthesia (see below). During MAC sedation clinical trials, significant respiratory events included cough, upper airway obstruction, apnea, hypoventilation, and dyspnea.
- Generally the adverse experience profile from reports of 506 Propofol Injectable Emulsion pediatric patients from 6 days through 16 years of age in the US/Canadian anesthesia clinical trials is similar to the profile established with Propofol Injectable Emulsion during anesthesia in adults (see Pediatric percentages below). Although not reported as an adverse event in clinical trials, apnea is frequently observed in pediatric patients.
- The following estimates of adverse events include data from clinical trials in ICU sedation (N=159 adult patients). Probably related incidence rates for ICU sedation were determined by individual case report form review. Probable causality was based upon an apparent dose response relationship and/or positive responses to rechallenge. In many instances the presence of concomitant disease and concomitant therapy made the causal relationship unknown. Therefore, incidence rates for ICU sedation generally represent estimates of the percentage of clinical trial patients which appeared to have a probable causal relationship.
## Postmarketing Experience
There is limited information regarding Propofol Postmarketing Experience in the drug label.
# Drug Interactions
- The induction dose requirements of Propofol Injectable Emulsion may be reduced in patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., morphine, meperidine, and fentanyl, etc.) and combinations of opioids and sedatives (e.g., benzodiazepines, barbiturates, chloral hydrate, droperidol, etc.). These agents may increase the anesthetic or sedative effects of Propofol Injectable Emulsion and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output.
- During maintenance of anesthesia or sedation, the rate of Propofol Injectable Emulsion administration should be adjusted according to the desired level of anesthesia or sedation and may be reduced in the presence of supplemental analgesic agents (e.g., nitrous oxide or opioids). The concurrent administration of potent inhalational agents (e.g., isoflurane, enflurane, and halothane) during maintenance with Propofol Injectable Emulsion has not been extensively evaluated. These inhalational agents can also be expected to increase the anesthetic or sedative and cardiorespiratory effects of Propofol Injectable Emulsion.
- Propofol Injectable Emulsion does not cause a clinically significant change in onset, intensity or duration of action of the commonly used neuromuscular blocking agents (e.g., succinylcholine and nondepolarizing muscle relaxants).
- No significant adverse interactions with commonly used premedications or drugs used during anesthesia or sedation (including a range of muscle relaxants, inhalational agents, analgesic agents, and local anesthetic agents) have been observed in adults. In pediatric patients, administration of fentanyl concomitantly with Propofol Injectable Emulsion may result in serious bradycardia.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats and rabbits at intravenous doses of 15 mg/kg/day (approximately equivalent to the recommended human induction dose on a mg/m2 basis) and have revealed no evidence of impaired fertility or harm to the fetus due to propofol. Propofol, however, has been shown to cause maternal deaths in rats and rabbits and decreased pup survival during the lactating period in dams treated with 15 mg/kg/day (approximately equivalent to the recommended human induction dose on a mg/m2 basis). The pharmacological activity (anesthesia) of the drug on the mother is probably responsible for the adverse effects seen in the offspring. There are, however, no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, Propofol Injectable Emulsion should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Propofol in women who are pregnant.
### Labor and Delivery
- Propofol Injectable Emulsion is not recommended for obstetrics, including cesarean section deliveries. Propofol Injectable Emulsion crosses the placenta, and as with other general anesthetic agents, the administration of Propofol Injectable Emulsion may be associated with neonatal depression.
### Nursing Mothers
- Propofol Injectable Emulsion is not recommended for use in nursing mothers because Propofol Injectable Emulsion has been reported to be excreted in human milk and the effects of oral absorption of small amounts of propofol are not known.
### Pediatric Use
- The safety and effectiveness of Propofol Injectable Emulsion have been established for induction of anesthesia in pediatric patients aged 3 years and older and for the maintenance of anesthesia aged 2 months and older.
- Propofol Injectable Emulsion is not recommended for the induction of anesthesia in patients younger than 3 years of age and for the maintenance of anesthesia in patients younger than 2 months of age as safety and effectiveness have not been established.
- In pediatric patients, administration of fentanyl concomitantly with Propofol Injectable Emulsion may result in serious bradycardia (see Precautions, General).
- Propofol Injectable Emulsion is not indicated for use in pediatric patients for ICU sedation or for MAC sedation for surgical, nonsurgical or diagnostic procedures as safety and effectiveness have not been established.
- There have been anecdotal reports of serious adverse events and death in pediatric patients with upper respiratory tract infections receiving Propofol Injectable Emulsion for ICU sedation.
- In one multicenter clinical trial of ICU sedation in critically ill pediatric patients that excluded patients with upper respiratory tract infections, the incidence of mortality observed in patients who received Propofol Injectable Emulsion (n=222) was 9%, while that for patients who received standard sedative agents (n=105) was 4%. While causality has not been established, Propofol Injectable Emulsion is not indicated for sedation in pediatric patients until further studies have been performed to document its safety in that population (see Clinical pharmacology, Pharmacokinetics, Pediatric Patients and Dosage and administration).
- In pediatric patients, abrupt discontinuation of Propofol Injectable Emulsion following prolonged infusion may result in flushing of the hands and feet, agitation, tremulousness and hyperirritability. Increased incidences of bradycardia (5%), agitation (4%), and jitteriness (9%) have also been observed.
### Geriatic Use
- The effect of age on induction dose requirements for propofol was assessed in an open-label study involving 211 unpremedicated patients with approximately 30 patients in each decade between the ages of 16 and 80. The average dose to induce anesthesia was calculated for patients up to 54 years of age and for patients 55 years of age or older. The average dose to induce anesthesia in patients up to 54 years of age was 1.99 mg/kg and in patients above 54 it was 1.66 mg/kg. Subsequent clinical studies have demonstrated lower dosing requirements for subjects greater than 60 years of age.
- A lower induction dose and a slower maintenance rate of administration of Propofol Injectable Emulsion should be used in elderly patients. In this group of patients, rapid (single or repeated) bolus administration should not be used in order to minimize undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation. All dosing should be titrated according to patient condition and response (see Dosage and Administration, Elderly, Debilitated or ASA-PS III or IV Patients and Clinical Pharmacology, Geriatrics).
### Gender
There is no FDA guidance on the use of Propofol with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Propofol with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Propofol in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Propofol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Propofol in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Propofol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Propofol Administration in the drug label.
### Monitoring
There is limited information regarding Propofol Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Propofol and IV administrations.
# Overdosage
- If overdosage occurs, Propofol Injectable Emulsion administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents.
# Pharmacology
## Mechanism of Action
There is limited information regarding Propofol Mechanism of Action in the drug label.
## Structure
- DIPRIVAN® (Propofol) Injectable Emulsion, USP is a sterile, nonpyrogenic emulsion containing 10 mg/mL of propofol suitable for intravenous administration. Propofol is chemically described as 2,6‑diisopropylphenol. The structural formula is:
- Propofol is slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion. The pKa is 11. The octanol/water partition coefficient for propofol is 6761:1 at a pH of 6 to 8.5. In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL); and disodium edetate (0.005%); with sodium hydroxide to adjust pH. Propofol Injectable Emulsion, USP is isotonic and has a pH of 7 to 8.5.
## Pharmacodynamics
- Pharmacodynamic properties of propofol are dependent upon the therapeutic blood propofol concentrations. Steady-state propofol blood concentrations are generally proportional to infusion rates. Undesirable side effects, such as cardiorespiratory depression, are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in infusion rates. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments in order to assess clinical effects.
- The hemodynamic effects of Propofol Injectable Emulsion during induction of anesthesia vary. If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and no appreciable decrease in cardiac output. If ventilation is assisted or controlled (positive pressure ventilation), there is an increase in the incidence and the degree of depression of cardiac output. Addition of an opioid, used as a premedicant, further decreases cardiac output and respiratory drive.
- If anesthesia is continued by infusion of Propofol Injectable Emulsion, the stimulation of endotracheal intubation and surgery may return arterial pressure towards normal. However, cardiac output may remain depressed. Comparative clinical studies have shown that the hemodynamic effects of Propofol Injectable Emulsion during induction of anesthesia are generally more pronounced than with other intravenous (IV) induction agents.
- Induction of anesthesia with Propofol Injectable Emulsion is frequently associated with apnea in both adults and pediatric patients. In adult patients who received Propofol Injectable Emulsion (2 to 2.5 mg/kg), apnea lasted less than 30 seconds in 7% of patients, 30 to 60 seconds in 24% of patients, and more than 60 seconds in 12% of patients. In pediatric patients from birth through 16 years of age assessable for apnea who received bolus doses of Propofol Injectable Emulsion (1 to 3.6 mg/kg), apnea lasted less than 30 seconds in 12% of patients, 30 to 60 seconds in 10% of patients, and more than 60 seconds in 5% of patients.
- During maintenance of general anesthesia, Propofol Injectable Emulsion causes a decrease in spontaneous minute ventilation usually associated with an increase in carbon dioxide tension which may be marked depending upon the rate of administration and concurrent use of other medications (e.g., opioids, sedatives, etc.).
- During monitored anesthesia care (MAC) sedation, attention must be given to the cardiorespiratory effects of Propofol Injectable Emulsion. Hypotension, oxyhemoglobin desaturation, apnea, and airway obstruction can occur, especially following a rapid bolus of Propofol Injectable Emulsion. During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus administration in order to minimize undesirable cardiorespiratory effects. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see Warnings).
- Clinical and preclinical studies suggest that Propofol Injectable Emulsion is rarely associated with elevation of plasma histamine levels.
- Preliminary findings in patients with normal intraocular pressure indicate that Propofol Injectable Emulsion produces a decrease in intraocular pressure which may be associated with a concomitant decrease in systemic vascular resistance.
- Clinical studies indicate that Propofol Injectable Emulsion when used in combination with hypocarbia increases cerebrovascular resistance and decreases cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure. Propofol Injectable Emulsion does not affect cerebrovascular reactivity to changes in arterial carbon dioxide tension (see Clinical Trials, Neuroanesthesia).
- Clinical studies indicate that Propofol Injectable Emulsion does not suppress the adrenal response to ACTH.
- Animal studies and limited experience in susceptible patients have not indicated any propensity of Propofol Injectable Emulsion to induce malignant hyperthermia.
- Hemosiderin deposits have been observed in the livers of dogs receiving Propofol Injectable Emulsion containing 0.005% disodium edetate over a four-week period; the clinical significance of this is unknown.
## Pharmacokinetics
- The pharmacokinetics of propofol are well described by a three compartment linear model with compartments representing the plasma, rapidly equilibrating tissues, and slowly equilibrating tissues.
- Following an IV bolus dose, there is rapid equilibration between the plasma and the brain, accounting for the rapid onset of anesthesia.
- Plasma levels initially decline rapidly as a result of both distribution and metabolic clearance. Distribution accounts for about half of this decline following a bolus of propofol. However, distribution is not constant over time, but decreases as body tissues equilibrate with plasma and become saturated. The rate at which equilibration occurs is a function of the rate and duration of the infusion. When equilibration occurs there is no longer a net transfer of propofol between tissues and plasma.
- Discontinuation of the recommended doses of Propofol Injectable Emulsion after the maintenance of anesthesia for approximately one hour, or for sedation in the ICU for one day, results in a prompt decrease in blood propofol concentrations and rapid awakening. Longer infusions (10 days of ICU sedation) result in accumulation of significant tissue stores of propofol, such that the reduction in circulating propofol is slowed and the time to awakening is increased.
- By daily titration of Propofol Injectable Emulsion dosage to achieve only the minimum effective therapeutic concentration, rapid awakening within 10 to 15 minutes can occur even after long-term administration. If, however, higher than necessary infusion levels have been maintained for a long time, propofol redistribution from fat and muscle to the plasma can be significant and slow recovery.
- The figure below illustrates the fall of plasma propofol levels following infusions of various durations to provide ICU sedation.
- The large contribution of distribution (about 50%) to the fall of propofol plasma levels following brief infusions means that after very long infusions a reduction in the infusion rate is appropriate by as much as half the initial infusion rate in order to maintain a constant plasma level. Therefore, failure to reduce the infusion rate in patients receiving Propofol Injectable Emulsion for extended periods may result in excessively high blood concentrations of the drug. Thus, titration to clinical response and daily evaluation of sedation levels are important during use of Propofol Injectable Emulsion infusion for ICU sedation.
- Propofol clearance ranges from 23 to 50 mL/kg/min (1.6 to 3.4 L/min in 70 kg adults). It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. Propofol has a steady-state volume of distribution (10-day infusion) approaching 60 L/kg in healthy adults. A difference in pharmacokinetics due to gender has not been observed. The terminal half-life of propofol after a 10-day infusion is 1 to 3 days.
- With increasing patient age, the dose of propofol needed to achieve a defined anesthetic end point (dose-requirement) decreases. This does not appear to be an age-related change in pharmacodynamics or brain sensitivity, as measured by EEG burst suppression. With increasing patient age, pharmacokinetic changes are such that, for a given IV bolus dose, higher peak plasma concentrations occur, which can explain the decreased dose requirement. These higher peak plasma concentrations in the elderly can predispose patients to cardiorespiratory effects including hypotension, apnea, airway obstruction, and/or arterial oxygen desaturation. The higher plasma levels reflect an age-related decrease in volume of distribution and intercompartmental clearance. Lower doses are therefore recommended for initiation and maintenance of sedation and anesthesia in elderly patients (see DOSAGE AND ADMINISTRATION).
- The pharmacokinetics of propofol were studied in children between 3 and 12 years of age who received Propofol Injectable Emulsion for periods of approximately 1 to 2 hours. The observed distribution and clearance of propofol in these children were similar to adults.
- The pharmacokinetics of propofol do not appear to be different in people with chronic hepatic cirrhosis or chronic renal impairment compared to adults with normal hepatic and renal function. The effects of acute hepatic or renal failure on the pharmacokinetics of propofol have not been studied.
## Nonclinical Toxicology
There is limited information regarding Propofol Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding Propofol Clinical Studies in the drug label.
# How Supplied
Propofol Injectable Emulsion, USP is available as follows:
Propofol undergoes oxidative degradation, in the presence of oxygen, and is therefore packaged under nitrogen to eliminate this degradation path.
## Storage
- Store between 4° to 25°C (40° to 77°F). Do not freeze. Shake well before use.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Propofol Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Propofol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Propofol Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Propofol Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Propofol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Propofol is a general anesthetic that is FDA approved for the {{{indicationType}}} of general anesthesia, monitored anesthesia care sedation, sedation for a mechanically ventilated patient, intensive care unit. There is a Black Box Warning for this drug as shown here. Common adverse reactions include dermatologic: injection site pain (up to 28.5% ), gastrointestinal: nausea and vomiting (2% to 2.5% ), musculoskeletal: involuntary movement, muscle (17%).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- General anesthesia: (healthy adults less than 55 years of age) induction, 40 mg IV every 10 seconds until induction onset (2 to 2.5 mg/kg); dose varies for age and surgery type.
- General anesthesia: (healthy adults less than 55 years of age) maintenance, 100 to 200 mcg/kg/min IV infusion (6 to 12 mg/kg/hr); dose varies for age and surgery type.
- General anesthesia: (healthy adults less than 55 years of age) maintenance, 20 to 50 mg increments IV bolus as needed.
- Migraine: 10 mg slow IV push, every 5 to 10 minutes, max 80 mg; mixed with 1 mL lidocaine 2% per 10 mL of propofol 1%; infuse at rate of 1 mL/10 sec.
- Monitored anesthesia care sedation: (healthy adults less than 55 years of age) MAC initiation: 100 to 150 mcg/kg/min (6 to 9 mg/kg/hr) IV infusion or 0.5 mg/kg slow IV injection for 3 to 5 min followed immediately by maintenance infusion.
- Monitored anesthesia care sedation: (healthy adults less than 55 years of age) MAC maintenance: 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/hr) IV infusion or 10 to 20 mg incremental IV bolus doses.
- Procedural sedation: 1 mg/kg IV followed by 0.5 mg/kg every 3 to 5 minutes as needed for sedation.
- Sedation for a mechanically ventilated patient, Intensive care unit: 5 mcg/kg/min (0.3 mg/kg/hr) IV infusion for 5 min then titrate in 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) increments to achieve desired level of sedation; allow minimum of 5 min between dose adjustments; usual maintenance rates 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Propofol in adult patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Propofol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Propofol FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Propofol in pediatric patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Propofol in pediatric patients.
# Contraindications
There is limited information regarding Propofol Contraindications in the drug label.
# Warnings
There is limited information regarding Propofol Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
- Adverse event information is derived from controlled clinical trials and worldwide marketing experience. In the description below, rates of the more common events represent US/Canadian clinical study results. Less frequent events are also derived from publications and marketing experience in over 8 million patients; there are insufficient data to support an accurate estimate of their incidence rates. These studies were conducted using a variety of premedicants, varying lengths of surgical/diagnostic procedures, and various other anesthetic/sedative agents. Most adverse events were mild and transient.
- The following estimates of adverse events for Propofol Injectable Emulsion include data from clinical trials in general anesthesia/MAC sedation (N=2889 adult patients). The adverse events listed below as probably causally related are those events in which the actual incidence rate in patients treated with Propofol Injectable Emulsion was greater than the comparator incidence rate in these trials. Therefore, incidence rates for anesthesia and MAC sedation in adults generally represent estimates of the percentage of clinical trial patients which appeared to have probable causal relationship.
- The adverse experience profile from reports of 150 patients in the MAC sedation clinical trials is similar to the profile established with Propofol Injectable Emulsion during anesthesia (see below). During MAC sedation clinical trials, significant respiratory events included cough, upper airway obstruction, apnea, hypoventilation, and dyspnea.
- Generally the adverse experience profile from reports of 506 Propofol Injectable Emulsion pediatric patients from 6 days through 16 years of age in the US/Canadian anesthesia clinical trials is similar to the profile established with Propofol Injectable Emulsion during anesthesia in adults (see Pediatric percentages [Peds %] below). Although not reported as an adverse event in clinical trials, apnea is frequently observed in pediatric patients.
- The following estimates of adverse events include data from clinical trials in ICU sedation (N=159 adult patients). Probably related incidence rates for ICU sedation were determined by individual case report form review. Probable causality was based upon an apparent dose response relationship and/or positive responses to rechallenge. In many instances the presence of concomitant disease and concomitant therapy made the causal relationship unknown. Therefore, incidence rates for ICU sedation generally represent estimates of the percentage of clinical trial patients which appeared to have a probable causal relationship.
## Postmarketing Experience
There is limited information regarding Propofol Postmarketing Experience in the drug label.
# Drug Interactions
- The induction dose requirements of Propofol Injectable Emulsion may be reduced in patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., morphine, meperidine, and fentanyl, etc.) and combinations of opioids and sedatives (e.g., benzodiazepines, barbiturates, chloral hydrate, droperidol, etc.). These agents may increase the anesthetic or sedative effects of Propofol Injectable Emulsion and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output.
- During maintenance of anesthesia or sedation, the rate of Propofol Injectable Emulsion administration should be adjusted according to the desired level of anesthesia or sedation and may be reduced in the presence of supplemental analgesic agents (e.g., nitrous oxide or opioids). The concurrent administration of potent inhalational agents (e.g., isoflurane, enflurane, and halothane) during maintenance with Propofol Injectable Emulsion has not been extensively evaluated. These inhalational agents can also be expected to increase the anesthetic or sedative and cardiorespiratory effects of Propofol Injectable Emulsion.
- Propofol Injectable Emulsion does not cause a clinically significant change in onset, intensity or duration of action of the commonly used neuromuscular blocking agents (e.g., succinylcholine and nondepolarizing muscle relaxants).
- No significant adverse interactions with commonly used premedications or drugs used during anesthesia or sedation (including a range of muscle relaxants, inhalational agents, analgesic agents, and local anesthetic agents) have been observed in adults. In pediatric patients, administration of fentanyl concomitantly with Propofol Injectable Emulsion may result in serious bradycardia.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats and rabbits at intravenous doses of 15 mg/kg/day (approximately equivalent to the recommended human induction dose on a mg/m2 basis) and have revealed no evidence of impaired fertility or harm to the fetus due to propofol. Propofol, however, has been shown to cause maternal deaths in rats and rabbits and decreased pup survival during the lactating period in dams treated with 15 mg/kg/day (approximately equivalent to the recommended human induction dose on a mg/m2 basis). The pharmacological activity (anesthesia) of the drug on the mother is probably responsible for the adverse effects seen in the offspring. There are, however, no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, Propofol Injectable Emulsion should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Propofol in women who are pregnant.
### Labor and Delivery
- Propofol Injectable Emulsion is not recommended for obstetrics, including cesarean section deliveries. Propofol Injectable Emulsion crosses the placenta, and as with other general anesthetic agents, the administration of Propofol Injectable Emulsion may be associated with neonatal depression.
### Nursing Mothers
- Propofol Injectable Emulsion is not recommended for use in nursing mothers because Propofol Injectable Emulsion has been reported to be excreted in human milk and the effects of oral absorption of small amounts of propofol are not known.
### Pediatric Use
- The safety and effectiveness of Propofol Injectable Emulsion have been established for induction of anesthesia in pediatric patients aged 3 years and older and for the maintenance of anesthesia aged 2 months and older.
- Propofol Injectable Emulsion is not recommended for the induction of anesthesia in patients younger than 3 years of age and for the maintenance of anesthesia in patients younger than 2 months of age as safety and effectiveness have not been established.
- In pediatric patients, administration of fentanyl concomitantly with Propofol Injectable Emulsion may result in serious bradycardia (see Precautions, General).
- Propofol Injectable Emulsion is not indicated for use in pediatric patients for ICU sedation or for MAC sedation for surgical, nonsurgical or diagnostic procedures as safety and effectiveness have not been established.
- There have been anecdotal reports of serious adverse events and death in pediatric patients with upper respiratory tract infections receiving Propofol Injectable Emulsion for ICU sedation.
- In one multicenter clinical trial of ICU sedation in critically ill pediatric patients that excluded patients with upper respiratory tract infections, the incidence of mortality observed in patients who received Propofol Injectable Emulsion (n=222) was 9%, while that for patients who received standard sedative agents (n=105) was 4%. While causality has not been established, Propofol Injectable Emulsion is not indicated for sedation in pediatric patients until further studies have been performed to document its safety in that population (see Clinical pharmacology, Pharmacokinetics, Pediatric Patients and Dosage and administration).
- In pediatric patients, abrupt discontinuation of Propofol Injectable Emulsion following prolonged infusion may result in flushing of the hands and feet, agitation, tremulousness and hyperirritability. Increased incidences of bradycardia (5%), agitation (4%), and jitteriness (9%) have also been observed.
### Geriatic Use
- The effect of age on induction dose requirements for propofol was assessed in an open-label study involving 211 unpremedicated patients with approximately 30 patients in each decade between the ages of 16 and 80. The average dose to induce anesthesia was calculated for patients up to 54 years of age and for patients 55 years of age or older. The average dose to induce anesthesia in patients up to 54 years of age was 1.99 mg/kg and in patients above 54 it was 1.66 mg/kg. Subsequent clinical studies have demonstrated lower dosing requirements for subjects greater than 60 years of age.
- A lower induction dose and a slower maintenance rate of administration of Propofol Injectable Emulsion should be used in elderly patients. In this group of patients, rapid (single or repeated) bolus administration should not be used in order to minimize undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation. All dosing should be titrated according to patient condition and response (see Dosage and Administration, Elderly, Debilitated or ASA-PS III or IV Patients and Clinical Pharmacology, Geriatrics).
### Gender
There is no FDA guidance on the use of Propofol with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Propofol with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Propofol in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Propofol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Propofol in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Propofol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Propofol Administration in the drug label.
### Monitoring
There is limited information regarding Propofol Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Propofol and IV administrations.
# Overdosage
- If overdosage occurs, Propofol Injectable Emulsion administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents.
# Pharmacology
## Mechanism of Action
There is limited information regarding Propofol Mechanism of Action in the drug label.
## Structure
- DIPRIVAN® (Propofol) Injectable Emulsion, USP is a sterile, nonpyrogenic emulsion containing 10 mg/mL of propofol suitable for intravenous administration. Propofol is chemically described as 2,6‑diisopropylphenol. The structural formula is:
- Propofol is slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion. The pKa is 11. The octanol/water partition coefficient for propofol is 6761:1 at a pH of 6 to 8.5. In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL); and disodium edetate (0.005%); with sodium hydroxide to adjust pH. Propofol Injectable Emulsion, USP is isotonic and has a pH of 7 to 8.5.
## Pharmacodynamics
- Pharmacodynamic properties of propofol are dependent upon the therapeutic blood propofol concentrations. Steady-state propofol blood concentrations are generally proportional to infusion rates. Undesirable side effects, such as cardiorespiratory depression, are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in infusion rates. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments in order to assess clinical effects.
- The hemodynamic effects of Propofol Injectable Emulsion during induction of anesthesia vary. If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and no appreciable decrease in cardiac output. If ventilation is assisted or controlled (positive pressure ventilation), there is an increase in the incidence and the degree of depression of cardiac output. Addition of an opioid, used as a premedicant, further decreases cardiac output and respiratory drive.
- If anesthesia is continued by infusion of Propofol Injectable Emulsion, the stimulation of endotracheal intubation and surgery may return arterial pressure towards normal. However, cardiac output may remain depressed. Comparative clinical studies have shown that the hemodynamic effects of Propofol Injectable Emulsion during induction of anesthesia are generally more pronounced than with other intravenous (IV) induction agents.
- Induction of anesthesia with Propofol Injectable Emulsion is frequently associated with apnea in both adults and pediatric patients. In adult patients who received Propofol Injectable Emulsion (2 to 2.5 mg/kg), apnea lasted less than 30 seconds in 7% of patients, 30 to 60 seconds in 24% of patients, and more than 60 seconds in 12% of patients. In pediatric patients from birth through 16 years of age assessable for apnea who received bolus doses of Propofol Injectable Emulsion (1 to 3.6 mg/kg), apnea lasted less than 30 seconds in 12% of patients, 30 to 60 seconds in 10% of patients, and more than 60 seconds in 5% of patients.
- During maintenance of general anesthesia, Propofol Injectable Emulsion causes a decrease in spontaneous minute ventilation usually associated with an increase in carbon dioxide tension which may be marked depending upon the rate of administration and concurrent use of other medications (e.g., opioids, sedatives, etc.).
- During monitored anesthesia care (MAC) sedation, attention must be given to the cardiorespiratory effects of Propofol Injectable Emulsion. Hypotension, oxyhemoglobin desaturation, apnea, and airway obstruction can occur, especially following a rapid bolus of Propofol Injectable Emulsion. During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus administration in order to minimize undesirable cardiorespiratory effects. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see Warnings).
- Clinical and preclinical studies suggest that Propofol Injectable Emulsion is rarely associated with elevation of plasma histamine levels.
- Preliminary findings in patients with normal intraocular pressure indicate that Propofol Injectable Emulsion produces a decrease in intraocular pressure which may be associated with a concomitant decrease in systemic vascular resistance.
- Clinical studies indicate that Propofol Injectable Emulsion when used in combination with hypocarbia increases cerebrovascular resistance and decreases cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure. Propofol Injectable Emulsion does not affect cerebrovascular reactivity to changes in arterial carbon dioxide tension (see Clinical Trials, Neuroanesthesia).
- Clinical studies indicate that Propofol Injectable Emulsion does not suppress the adrenal response to ACTH.
- Animal studies and limited experience in susceptible patients have not indicated any propensity of Propofol Injectable Emulsion to induce malignant hyperthermia.
- Hemosiderin deposits have been observed in the livers of dogs receiving Propofol Injectable Emulsion containing 0.005% disodium edetate over a four-week period; the clinical significance of this is unknown.
## Pharmacokinetics
- The pharmacokinetics of propofol are well described by a three compartment linear model with compartments representing the plasma, rapidly equilibrating tissues, and slowly equilibrating tissues.
- Following an IV bolus dose, there is rapid equilibration between the plasma and the brain, accounting for the rapid onset of anesthesia.
- Plasma levels initially decline rapidly as a result of both distribution and metabolic clearance. Distribution accounts for about half of this decline following a bolus of propofol. However, distribution is not constant over time, but decreases as body tissues equilibrate with plasma and become saturated. The rate at which equilibration occurs is a function of the rate and duration of the infusion. When equilibration occurs there is no longer a net transfer of propofol between tissues and plasma.
- Discontinuation of the recommended doses of Propofol Injectable Emulsion after the maintenance of anesthesia for approximately one hour, or for sedation in the ICU for one day, results in a prompt decrease in blood propofol concentrations and rapid awakening. Longer infusions (10 days of ICU sedation) result in accumulation of significant tissue stores of propofol, such that the reduction in circulating propofol is slowed and the time to awakening is increased.
- By daily titration of Propofol Injectable Emulsion dosage to achieve only the minimum effective therapeutic concentration, rapid awakening within 10 to 15 minutes can occur even after long-term administration. If, however, higher than necessary infusion levels have been maintained for a long time, propofol redistribution from fat and muscle to the plasma can be significant and slow recovery.
- The figure below illustrates the fall of plasma propofol levels following infusions of various durations to provide ICU sedation.
- The large contribution of distribution (about 50%) to the fall of propofol plasma levels following brief infusions means that after very long infusions a reduction in the infusion rate is appropriate by as much as half the initial infusion rate in order to maintain a constant plasma level. Therefore, failure to reduce the infusion rate in patients receiving Propofol Injectable Emulsion for extended periods may result in excessively high blood concentrations of the drug. Thus, titration to clinical response and daily evaluation of sedation levels are important during use of Propofol Injectable Emulsion infusion for ICU sedation.
- Propofol clearance ranges from 23 to 50 mL/kg/min (1.6 to 3.4 L/min in 70 kg adults). It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. Propofol has a steady-state volume of distribution (10-day infusion) approaching 60 L/kg in healthy adults. A difference in pharmacokinetics due to gender has not been observed. The terminal half-life of propofol after a 10-day infusion is 1 to 3 days.
- With increasing patient age, the dose of propofol needed to achieve a defined anesthetic end point (dose-requirement) decreases. This does not appear to be an age-related change in pharmacodynamics or brain sensitivity, as measured by EEG burst suppression. With increasing patient age, pharmacokinetic changes are such that, for a given IV bolus dose, higher peak plasma concentrations occur, which can explain the decreased dose requirement. These higher peak plasma concentrations in the elderly can predispose patients to cardiorespiratory effects including hypotension, apnea, airway obstruction, and/or arterial oxygen desaturation. The higher plasma levels reflect an age-related decrease in volume of distribution and intercompartmental clearance. Lower doses are therefore recommended for initiation and maintenance of sedation and anesthesia in elderly patients (see DOSAGE AND ADMINISTRATION).
- The pharmacokinetics of propofol were studied in children between 3 and 12 years of age who received Propofol Injectable Emulsion for periods of approximately 1 to 2 hours. The observed distribution and clearance of propofol in these children were similar to adults.
- The pharmacokinetics of propofol do not appear to be different in people with chronic hepatic cirrhosis or chronic renal impairment compared to adults with normal hepatic and renal function. The effects of acute hepatic or renal failure on the pharmacokinetics of propofol have not been studied.
## Nonclinical Toxicology
There is limited information regarding Propofol Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding Propofol Clinical Studies in the drug label.
# How Supplied
Propofol Injectable Emulsion, USP is available as follows:
Propofol undergoes oxidative degradation, in the presence of oxygen, and is therefore packaged under nitrogen to eliminate this degradation path.
## Storage
- Store between 4° to 25°C (40° to 77°F). Do not freeze. Shake well before use.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Propofol Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Propofol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Propofol Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Propofol Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Diprivan | |
566b244e071e8695e5dc6b785a7967325bf281fc | wikidoc | Pathogen | Pathogen
A pathogen or infectious agent is a biological agent that causes disease or illness to its host. The term is most often used for agents that disrupt the normal physiology of a multicellular animal or plant. However, pathogens can infect unicellular organisms from all of the biological kingdoms. The term pathogen is derived from the Greek παθογένεια, "that which produces suffering."
There are several substrates and pathways where by pathogens can invade a host; the principal pathways have different episodic time frames, but soil contamination has the longest or most persistent potential for harboring a pathogen.
The body contains many natural defenses against some of the common pathogens (such as Pneumocystis) in the form of the human immune system and by some "helpful" bacteria present in the human body's normal flora. However, if the immune system or "good" bacteria is damaged in any way (such as by chemotherapy, human immunodeficiency virus (HIV), or antibiotics being taken to kill other pathogens), pathogenic bacteria that were being held at bay can proliferate and cause harm to the host. Such cases are called opportunistic infections.
Some pathogens (such as the bacterium Yersinia pestis, which may have caused the Black Plague, and the Variola and Malaria viruses) have been responsible for massive numbers of casualties and have had numerous effects on afflicted groups. Of particular note in modern times is HIV, which is known to have infected several million humans globally, along with Severe Acute Respiratory Syndrome
(SARS) and the Influenza virus. Today, while many medical advances have been made to safeguard against infection by pathogens, through the use of vaccination, antibiotics, and fungicide, pathogens continue to threaten human life. Social advances such as food safety, hygiene, and water treatment have reduced the threat from some pathogens.
# Types of pathogens
Below is a listing of different types of notable pathogens as categorized by their structural characteristics, and some of their known effects on infected hosts.
# Transmission of pathogens
One of the primary pathways by which food or water become contaminated is from the release of untreated sewage into a drinking water supply or onto cropland, with the result that people who eat or drink contaminated sources become infected. In developing countries most sewage is discharged into the environment or on cropland as of 2007; even in developed countries there are periodic system failures resulting in a sanitary sewer overflow. This is the typical mode of transmission for the infectious agents of (at least):
- Cholera
- Hepatitis A
- Polio
- Rotavirus
# Transmission to vascular plants
In the case of terrestrial vascular plants, pathogenic infection can occur by contact with foliage, and also from root uptake of soil pathogens. The latter pathway explains why some plant families such as orchids are more disease resistant, since they rely upon fungal hyphae to supply nutrients rather than root structures, which have larger radii for conveying certain pathogens. | Pathogen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A pathogen or infectious agent is a biological agent that causes disease or illness to its host.[1] The term is most often used for agents that disrupt the normal physiology of a multicellular animal or plant. However, pathogens can infect unicellular organisms from all of the biological kingdoms. The term pathogen is derived from the Greek παθογένεια, "that which produces suffering."
There are several substrates and pathways where by pathogens can invade a host; the principal pathways have different episodic time frames, but soil contamination has the longest or most persistent potential for harboring a pathogen.
The body contains many natural defenses against some of the common pathogens (such as Pneumocystis) in the form of the human immune system and by some "helpful" bacteria present in the human body's normal flora. However, if the immune system or "good" bacteria is damaged in any way (such as by chemotherapy, human immunodeficiency virus (HIV), or antibiotics being taken to kill other pathogens), pathogenic bacteria that were being held at bay can proliferate and cause harm to the host. Such cases are called opportunistic infections.
Some pathogens (such as the bacterium Yersinia pestis, which may have caused the Black Plague, and the Variola and Malaria viruses) have been responsible for massive numbers of casualties and have had numerous effects on afflicted groups. Of particular note in modern times is HIV, which is known to have infected several million humans globally, along with Severe Acute Respiratory Syndrome
(SARS) and the Influenza virus. Today, while many medical advances have been made to safeguard against infection by pathogens, through the use of vaccination, antibiotics, and fungicide, pathogens continue to threaten human life. Social advances such as food safety, hygiene, and water treatment have reduced the threat from some pathogens.
# Types of pathogens
Below is a listing of different types of notable pathogens as categorized by their structural characteristics, and some of their known effects on infected hosts.
# Transmission of pathogens
One of the primary pathways by which food or water become contaminated is from the release of untreated sewage into a drinking water supply or onto cropland, with the result that people who eat or drink contaminated sources become infected. In developing countries most sewage is discharged into the environment or on cropland as of 2007; even in developed countries there are periodic system failures resulting in a sanitary sewer overflow. This is the typical mode of transmission for the infectious agents of (at least):
- Cholera
- Hepatitis A
- Polio
- Rotavirus
# Transmission to vascular plants
In the case of terrestrial vascular plants, pathogenic infection can occur by contact with foliage, and also from root uptake of soil pathogens. The latter pathway explains why some plant families such as orchids are more disease resistant, since they rely upon fungal hyphae to supply nutrients rather than root structures, which have larger radii for conveying certain pathogens. | https://www.wikidoc.org/index.php/Disease_agent | |
79d840589c2a4a4b410960ec060416d96da9452d | wikidoc | Disjoint | Disjoint
In mathematics, two sets are said to be disjoint if they have no element in common. For example, {1, 2, 3} and {4, 5, 6} are disjoint sets.
# Explanation
Formally, two sets A and B are disjoint if their intersection is the empty set, i.e. if
This definition extends to any collection of sets. A collection of sets is pairwise disjoint or mutually disjoint if any two distinct sets in the collection are disjoint.
Formally, let I be an index set, and for each i in I, let Ai be a set. Then the family of sets {Ai : i ∈ I} is pairwise disjoint if for any i and j in I with i ≠ j,
For example, the collection of sets { {1}, {2}, {3}, ... } is pairwise disjoint. If {Ai} is a pairwise disjoint collection (containing at least two sets), then clearly its intersection is empty:
However, the converse is not true: the intersection of the collection {{1, 2}, {2, 3}, {3, 1}} is empty, but the collection is not pairwise disjoint - in fact, there are no two disjoint sets in the collection.
A partition of a set X is any collection of non-empty subsets {Ai : i ∈ I} of X such that {Ai} are pairwise disjoint and | Disjoint
In mathematics, two sets are said to be disjoint if they have no element in common. For example, {1, 2, 3} and {4, 5, 6} are disjoint sets.
# Explanation
Formally, two sets A and B are disjoint if their intersection is the empty set, i.e. if
This definition extends to any collection of sets. A collection of sets is pairwise disjoint or mutually disjoint if any two distinct sets in the collection are disjoint.
Formally, let I be an index set, and for each i in I, let Ai be a set. Then the family of sets {Ai : i ∈ I} is pairwise disjoint if for any i and j in I with i ≠ j,
For example, the collection of sets { {1}, {2}, {3}, ... } is pairwise disjoint. If {Ai} is a pairwise disjoint collection (containing at least two sets), then clearly its intersection is empty:
However, the converse is not true: the intersection of the collection {{1, 2}, {2, 3}, {3, 1}} is empty, but the collection is not pairwise disjoint - in fact, there are no two disjoint sets in the collection.
A partition of a set X is any collection of non-empty subsets {Ai : i ∈ I} of X such that {Ai} are pairwise disjoint and | https://www.wikidoc.org/index.php/Disjoint | |
b01fe77dbc7bef1c4b8ae76f2b73c2ad9fe7a623 | wikidoc | Hospital | Hospital
# Overview
A hospital is an institution for health care providing treatment by specialised staff and equipment, and often but not always providing for longer-term patient stays.
Today, hospitals are usually funded by the state, health organizations (for profit or non-profit), health insurances or charities, including direct charitable donations. In history, however, they were often founded and funded by religious orders or charitable individuals and leaders. Similarly, modern-day hospitals are largely staffed by professional physicians, surgeons and nurses, whereas in history, this work was usually done by the founding religious orders or by volunteers.
# Etymology
During the Middle Ages the hospital could serve other functions, such as almshouse for the poor, hostel for pilgrims, or hospital school. The name comes from Latin hospes (host), which is also the root for the English words hotel, hostel, and hospitality. The modern word hotel derives from the French word hostel, which featured a silent s, which was eventually removed from the word. (The circumflex on modern French hôtel hints at the vanished s)
Grammar of the word differs slightly depending on the dialect. In the U.S., hospital usually requires an article; in Britain and elsewhere, the word is normally used without an article when it is the object of a preposition and when referring to a patient ("in/to the hospital" vs. "in/to hospital"); in Canada, both usages are found.
# Types
Some patients in a hospital come just for diagnosis and/or therapy and then leave ('outpatients'); while others are 'admitted' and stay overnight or for several weeks or months ('inpatients'). Hospitals are usually distinguished from other types of medical facilities by their ability to admit and care for inpatients.
## General
The best-known type of hospital is the general hospital, which is set up to deal with many kinds of disease and injury, and typically has an emergency ward to deal with immediate threats to health and the capacity to dispatch emergency medical services. A general hospital is typically the major health care facility in its region, with large numbers of beds for intensive care and long-term care; and specialized facilities for surgery, plastic surgery, childbirth, bioassay laboratories, and so forth. Larger cities may have many different hospitals of varying sizes and facilities.
## Specialized
Types of specialized hospitals include trauma centers, rehabilitation hospitals, children's hospitals, seniors' (geriatric) hospitals, and hospitals for dealing with specific medical needs such as psychiatric problems (see psychiatric hospital), certain disease categories, and so forth.
A hospital may be a single building or a campus. (Many hospitals with pre-20th-century origins began as one building and evolved into campuses.) Some hospitals are affiliated with universities for medical research and the training of medical personnel. Worldwide, most hospitals are run on a non-profit basis by governments or charities. Within the United States, most hospitals are not-for-profit.
## Teaching
A teaching hospital (or university hospital) is that who combines assistance to patients with teaching to medical students.
## Clinics
A medical facility smaller than a hospital is called a clinic, and is often run by a government agency for health services or a private partnership of physicians (in nations where private practice is allowed). Clinics generally provide only outpatient services.
# Departments
Hospitals may have any of the following departments or units:
- Behavioral Health Services
- Burn unit
- Cancer Center
- Coronary care unit
- Dispensary
- Emergency department
- Intensive Care Unit
Neonatal intensive care unit
Trauma center
- Neonatal intensive care unit
- Trauma center
- Labor and Delivery
- Laboratory Services
- Nursing unit
- Orthopedic Services
- Outpatient Department
- Pharmacy
- Psychiatric ward
- Rehabilitation Services
- Physical Therapy
- Post anesthesia care unit
- Radiology
- Respiratory Therapy
- Surgery
- Urgent care
Non-medical departments include:
- Medical records department
- Release of Information department
# History
In ancient cultures, religion and medicine were linked. The earliest known institutions aiming to provide cure were Egyptian temples. Greek temples dedicated to the healer-god Asclepius might admit the sick, who would wait for guidance from the god in a dream. The Romans adopted his worship. Under his Roman name Æsculapius, he was provided with a temple (291 BC) on an island in the Tiber in Rome, where similar rites were performed.
## Ancient Asia
The Sinhalese (Sri Lankans) are perhaps responsible for introducing the concept of dedicated hospitals to the world. According to the Mahavamsa, the ancient chronicle of Sinhalese royalty written in the 6th century A.D., King Pandukabhaya (4th century BC) had lying-in-homes and hospitals (Sivikasotthi-Sala) built in various parts of the country. This is the earliest documentary evidence we have of institutions specifically dedicated to the care of the sick anywhere in the world. Mihintale Hospital is perhaps the oldest in the world.
Institutions created specifically to care for the ill also appeared early in India. King Ashoka is said to have founded at least 18 hospitals ca. 230 BC, with physicians and nursing staff, the expense being borne by the royal treasury. However, there are historians who strictly dispute the claim that Ashoka built any hospitals at all, and argue that it is based on a mistranslation, with references to 'rest houses' being mistaken for hospitals. The error is thought to have occurred because similar edicts and records talk of Ashoka importing medicinal supplies.
State-supported hospitals later appeared in China during the first millennium A.D. The first teaching hospital where students were authorized to methodically practice on patients under the supervision of physicians as part of their education, was the Academy of Gundishapur in the Persian Empire. One expert has argued that "to a very large extent, the credit for the whole hospital system must be given to Persia".
## Roman Empire
The Romans created valetudinaria for the care of sick slaves, gladiators and soldiers around 100 BC, and many were identified by later archeology. While their existence is considered proven, there is some doubt as to whether they were as widespread as was once thought, as many were identified only according to the layout of building remains, and not by means of surviving records or finds of medical tools.
The adoption of Christianity as the state religion of the empire drove an expansion of the provision of care. The First Council of Nicaea in 325 A.D. urged the Church to provide for the poor, sick, widows and strangers. It ordered the construction of a hospital in every cathedral town. Among the earliest were those built by the physician Saint Sampson in Constantinople and by Basil, bishop of Caesarea. The latter was attached to a monastery and provided lodgings for poor and travelers, as well as treating the sick and infirm. There was a separate section for lepers.
## Medieval Islam
The earliest recorded hospitals in the medieval Islamic world refer to the hopital of al-Walid ibn 'Abdul Malik (ruled 705-715 CE) which he built in 86 AH (706-707 CE). It somewhat resembled the Byzantine nosocomia, but was more general as it extended its services to the lepers and the invalid and destitute people. All treatment and care was free of charge and there was more than one physician employed in this hospital.
In the medieval Islamic world, the word "Bimaristan" was used to indicate a hospital in the modern sense, an establishment where the ill were welcomed and cared for by qualified staff. In this way, Muslim physicians were the first to make a distinction between a hospital and other different forms of healing temples, sleep temples, hospices, assylums, lazarets and leper-houses, all of which in ancient times were more concerned with isolating the sick and the mad from society "rather than to offer them any way to a true cure." Some thus consider the medieval Bimaristan hospitals as "the first hospitals" in the modern sense of the word. The first public hospitals, psychiatric hospitals and medical universities were also introduced by medieval Muslim physicians.
Between the eighth and twelfth centuries CE Muslim hospitals developed a high standard of care. Hospitals built in Baghdad in the ninth and tenth centuries employed up to twenty-five staff physicians and had separate wards for different conditions. Al-Qairawan hospital and mosque, in Tunisia, were built under the Aghlabid rule in 830 CE and was simple but adequately equipped with halls organized into waiting rooms, a mosque, and a special bath. The hospital employed female nurses, including nurses from Sudan, a sign of great breakthrough. In addition to regular physicians who attended the sick, there were Fuqaha al-Badan, a kind of religious physio-therapists, group of religious scholars whose medical services included bloodletting, bone setting, and cauterisation. During Ottoman rule, when hospitals reached a particular distinction, Sultan Bayazid II built a mental hospital and medical madrasa in Edirne, and a number of other early hospitals were also built in Turkey. Unlike in Greek temples to healing gods, the clerics working in these facilities employed scientific methodology far beyond that of their contemporaries in their treatment of patients.
According to Sir John Bagot Glubb:
"By Mamun's time medical schools were extremely active in Baghdad. The first free public hospital was opened in Baghdad during the Caliphate of Haroon-ar-Rashid. As the system developed, physicians and surgeons were appointed who gave lectures to medical students and issued diplomas to those who were considered qualified to practice. The first hospital in Egypt was opened in 872 AD and thereafter public hospitals sprang up all over the empire from Spain and the Maghrib to Persia."
## Medieval Europe
Medieval hospitals in Europe followed a similar pattern. They were religious communities, with care provided by monks and nuns. (An old French term for hospital is hôtel-Dieu, "hostel of God.") Some were attached to monasteries; others were independent and had their own endowments, usually of property, which provided income for their support. Some hospitals were multi-function while others were founded for specific purposes such as leper hospitals, or as refuges for the poor or for pilgrims: not all cared for the sick. Not until later where most hospitals multi-functional, though the first Spanish hospital, founded by the Catholic Visigoth bishop Masona in 580 at Mérida, was a xenodochium designed as an inn for travellers (mostly pilgrims to the shrine of Eulalia of Mérida) as well as a hospital for citizens and local farmers. The hospital's endowment consisted of farms to feed its patients and guests.
## Colonial America
It is believed that the first Spanish style hospital founded in the Americas following Columbus arrival to the island now known as Hispaniola was the Hospital San Nicolás de Bari Calle Hostos in Santo Domingo, Distrito Nacional Dominican Republic.
Fray Nicolas de Ovando, Spanish governor and colonial administrator from 1502-1509, authorized its construction in or after 1504. It is believed that this hospital also served as a church during its lifetime. The first phase of its construction was completed in 1519. Erwin Walter Palm, wrote that "the Brotherhood of Our Lady of the Conception continued the construction of the hospital in 1533, adding modern elements, including additional buildings." Abandoned in the mid-18th century the hospital now lies in ruins near the Cathedral in the colonial zone in Santo Domingo, DR, amid additional historical New World sights.
The Hospital de Jesús Nazareno in Mexico City is the oldest hospital in North America. It was founded in 1524 with the economic support of conquistador Hernán Cortés to care for poor Spanish soldiers and the native inhabitants.
The first hospital in North America north of Mexico is the Hôtel-Dieu de Québec. It was established in New France in 1639 by three Augustinians from l'Hôtel-Dieu de Dieppe in France. The project of the niece of Cardinal de Richelieu was granted a royal charter by King Louis XIII and staffed by colonial physician Robert Giffard de Moncel.
## Modern era
In Europe the medieval concept of Christian care evolved during the sixteenth and seventeenth centuries into a secular one, but it was in the eighteenth century that the modern hospital began to appear, serving only medical needs and staffed with physicians and surgeons. The Charité (founded in Berlin in 1710) is an early example.
Guy's Hospital was founded in London in 1724 from a bequest by wealthy merchant Thomas Guy. Other hospitals sprang up in London and other British cities over the century, many paid for by private subscriptions. In the British American colonies the Pennsylvania General Hospital was chartered in Philadelphia in 1751, after £2,000 from private subscription was matched by funds from the Assembly.
When the Viennese General Hospital (Allgemeines Krankenhaus) opened in 1784 (instantly becoming the world's largest hospital), physicians acquired a new facility that gradually developed into the most important research center. During the 19th century, the Second Viennese Medical School emerged with the contributions of physicians such as Carl Freiherr von Rokitansky, Josef Škoda, Ferdinand Ritter von Hebra and Ignaz Philipp Semmelweis. Basic medical science expanded and specialization advanced. Furthermore, the first dermatology, eye, as well as ear, nose and throat clinics in the world were founded in Vienna, being considered was the birth of specialized medicine.
By the mid-nineteenth century most of Europe and the United States had established a variety of public and private hospital systems. In Continental Europe the new hospitals were generally built and run from public funds. The National Health Service, the principle provider of healthcare in the United Kingdom, was founded in 1948.
In the United States the traditional hospital is a non-profit hospital, usually sponsored by a religious denomination. One of the earliest of these "almshouses" in what would become the United States was started by William Penn in Philadelphia in 1713. These hospitals are tax-exempt due to their charitable purpose, but provide only a minimum of charitable medical care. They are supplemented by large public hospitals in major cities and research hospitals often affiliated with a medical school. In the late twentieth century, chains of for-profit hospitals arose in the USA.
# Criticism
While hospitals, by concentrating equipment, skilled staff and other resources in one place, clearly provide important help to patients with serious or rare health problems, hospitals are also criticised for a number of faults, some of which are endemic to the system, others which develop from what some consider wrong approaches to health care.
One cricitism often voiced is the 'industrialised' nature of care, with constantly shifting treatment staff, which dehumanises the patient and prevents more effective care as doctors and nurses are rarely intimately familiar with the patient. The high working pressures often put on the staff exacerbates such rushed and impersonal treatment. The architecture and setup of modern hospitals is often voiced as a contributing factor to the feelings of faceless treatment many people complain about.
Another criticism is that hospitals are in themselves a dangerous place for patients, which are often suffering from weakened immune systems - either due to their body having to undergo substantial surgery or because of the illness which placed them in the hospital itself. As an example, it is estimated that as much as 10% of all patients in the United States contract a nosocomical (hospital-caused) infection. Due to the environment in which antibiotics are used in large quantities, the infections are also often multi-resistant to various treatment methods, such as the relatively common MRSA infection.
# Funding
In the modern era, hospitals are, broadly, either funded by the government of the country in which they are situated, or survive financially by competing in the private sector (a number of hospitals are also still supported by the historical type of charitable or religious associations).
In the United Kingdom for example, a relatively comprehensive, "free at the point of delivery" healthcare system exists, funded by the state. Hospital care is thus relatively easily available to all legal residents (although as hospitals prioritize their limited resources, there is a tendency for 'waiting lists' to be generated for non-emergency treatment, and those who can afford it may take out private healthcare to get treatment faster). On the other hand, many countries, including for example the USA, have in the 20th Century followed a largely private-based, for-profit-approach to providing hospital care, with few state-money supported "charity" hospitals remaining today. Where for-profit hospitals in such countries admit uninsured patients in emergency situations (such as during and after the Hurricane Katrina in the USA), they incur direct financial losses, ensuring that there is a clear disincentive to admit such patients.
While for-profit-based systems have produced some of the best hospitals in the world, a proportion of the populace may have little or no access to healthcare services of adequate quality.
As quality of healthcare has increasingly become an issue around the world, hospitals have increasingly had to pay serious attention to this. Independent external assessment of quality is one of the most powerful ways of assessing the quality of healthcare, and hospital accreditation is one means by which this is achieved. In many parts of the world such accreditation is sourced from other countries, a phenomenon known as international healthcare accreditation, by groups such as the Joint Commission from the USA and the Trent Accreditation Scheme from Great Britain.
# Buildings
## Architecture
Modern hospital buildings are designed to minimize the effort of medical personnel and the possibility of contamination while maximizing the efficiency of the whole system. Travel time for personnel within the hospital and the transportation of patients between units is facilitated and minimized. The building also should be built to accommodate heavy departments such as radiology and operating rooms; while space for special wiring, plumbing and waste disposal must be allowed for in the design.
However, the reality is that many hospitals, even those considered 'modern', are the product of continual, and often badly managed growth over decades or even centuries, with utilitarian new sections added on as needs and finances dictate. As a result, Dutch architectural historian Cor Wagenaar has called many hospitals:
Some newer hospital designs now try to reestablish design that takes the patient's psychological needs into account, such as providing for more air, better views and more pleasant color schemes. These ideas harken back to the late 18th century, when the concept of providing fresh air and access to the 'healing powers of nature' were first employed by hospital architects in improving their buildings.
Another major change which is still ongoing in many parts of the world is the change from a ward-based system (where patients are treated and accommodated in communal rooms, separated at best by movable partititions) to a room-based environment, where patients are accommodated in private rooms. The ward-based system has been described as very efficient, especially for the medical staff, but is considered to be more stressful for patients and detrimental to their privacy. A major constraint on providing all patients with their own rooms is however found in the higher cost of building and operating such a hospital, which causes some hospitals to charge for the privilege of private rooms.
## Infrastructure
The surgical, special procedures, radiological, intensive care unit, and patient rooms typically have medical gases, emergency and normal electrical power; and heating, air conditioning and ventilation systems.
## Electrical
The reliability of the electrical power systems that serve a hospital is important. In order to provide higher electrical reliability, the National Institutes of Health, NIH, requires that all secondary substations > 500 kVA at their Bethesda, MD campus be the spot network type. The spot network substations cost more than other arrangements.
## Information
Pneumatic tube conveying systems are often used to move the actual paper prescriptions for medicines to the Pharmacies, and to move medicines, especially intra-venous, IV, bags to the patient care rooms. Tissue samples can be sent to the Laboratory. Medical notes can be transcribed, printed, and then transported via a Pneumatic Tube Conveying System.
As measured by the weight of the item be transferred, the 15 cm (6”) diameter tube systems have about 225% of the lifting and moving capacity of a 10 cm (4”) system. When the seals are new, the 10 cm tube carriers will move a 1 kg (2+ pound) IV bag. But when the seals on the tube carriers are worn, the tubes can stop moving in the piping, and require a trained technician to recover the tube carrier.
Modern hospitals have information infrastructure such as secured patient information system and PACS.
# References & Notes
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), pp.134-5.
- ↑ Prof. Arjuna Aluvihare, "Rohal Kramaya Lovata Dhayadha Kale Sri Lankikayo" Vidhusara Science Magazine, Nov. 1993.
- ↑ Resource Mobilization in Sri Lanka's Health Sector - Rannan-Eliya, Ravi P. & De Mel, Nishan, Harvard School of Public Health & Health Policy Programme, Institute of Policy Studies, February 1997, Page 19. Accessed 2008-02-22.
- ↑ Heinz E Müller-Dietz, Historia Hospitalium (1975).
- ↑ Encyclopedia of Medical History - McGrew, Roderick E. (Macmillan 1985), p.135.
- ↑ The Nurses should be able to Sing and Play Instruments - Wujastyk, Dominik; University College London. Accessed 2008-02-22.)
- ↑ C. Elgood, A Medical History of Persia, (Cambridge Univ. Press), p. 173.
- ↑ The Roman military Valetudinaria: fact or fiction - Baker, Patricia Anne, University of Newcastle upon Tyne, Sunday 20 December 1998
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), p.135.
- ↑ al-Hassani, Woodcock and Saoud (2007), 'Muslim heritage in Our World', FSTC Publishing, pp.154-156
- ↑ Micheau, Francoise, "The Scientific Institutions in the Medieval Near East", pp. 991–2 Missing or empty |title= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}, in Template:Harv
- ↑ Peter Barrett (2004), Science and Theology Since Copernicus: The Search for Understanding, p. 18, Continuum International Publishing Group, ISBN 056708969X.
- ↑ Ibrahim B. Syed PhD, "Islamic Medicine: 1000 years ahead of its times", Journal of the Islamic Medical Association, 2002 (2), p. 2-9 .
- ↑ Jump up to: 14.0 14.1 Sir Glubb, John Bagot (1969), A Short History of the Arab Peoples, retrieved 2008-01-25
- ↑ Turkish Contributions to Scientific Work in Islam - Sayili, Aydin, Foundation For Science, Technology and Civilisation, Septermber 2004, Page 9
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), p.139.
- ↑ References provided in this same article.
- ↑ References provided in the linked article.
- ↑ Surgery worries create insurance boom – The New Zealand Herald, Monday 21 January 2008
- ↑ Jump up to: 20.0 20.1 Hospitals in New Orleans see surge in uninsured patients but not public funds – USA Today, Wednesday 26 April 2006
- ↑ Jump up to: 21.0 21.1 Healing by design – Ode Magazine, July/August 2006 issue. Accessed 2008-02-10.
- ↑ Health administrators go shopping for new hospital designs – National Review of Medicine, Monday 15 November 2004, Volume 1 NO. 21
- Template:Harvard reference | Hospital
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A hospital is an institution for health care providing treatment by specialised staff and equipment, and often but not always providing for longer-term patient stays.
Today, hospitals are usually funded by the state, health organizations (for profit or non-profit), health insurances or charities, including direct charitable donations. In history, however, they were often founded and funded by religious orders or charitable individuals and leaders. Similarly, modern-day hospitals are largely staffed by professional physicians, surgeons and nurses, whereas in history, this work was usually done by the founding religious orders or by volunteers.
# Etymology
During the Middle Ages the hospital could serve other functions, such as almshouse for the poor, hostel for pilgrims, or hospital school. The name comes from Latin hospes (host), which is also the root for the English words hotel, hostel, and hospitality. The modern word hotel derives from the French word hostel, which featured a silent s, which was eventually removed from the word. (The circumflex on modern French hôtel hints at the vanished s)
Grammar of the word differs slightly depending on the dialect. In the U.S., hospital usually requires an article; in Britain and elsewhere, the word is normally used without an article when it is the object of a preposition and when referring to a patient ("in/to the hospital" vs. "in/to hospital"); in Canada, both usages are found.
# Types
Some patients in a hospital come just for diagnosis and/or therapy and then leave ('outpatients'); while others are 'admitted' and stay overnight or for several weeks or months ('inpatients'). Hospitals are usually distinguished from other types of medical facilities by their ability to admit and care for inpatients.
## General
The best-known type of hospital is the general hospital, which is set up to deal with many kinds of disease and injury, and typically has an emergency ward to deal with immediate threats to health and the capacity to dispatch emergency medical services. A general hospital is typically the major health care facility in its region, with large numbers of beds for intensive care and long-term care; and specialized facilities for surgery, plastic surgery, childbirth, bioassay laboratories, and so forth. Larger cities may have many different hospitals of varying sizes and facilities.
## Specialized
Types of specialized hospitals include trauma centers, rehabilitation hospitals, children's hospitals, seniors' (geriatric) hospitals, and hospitals for dealing with specific medical needs such as psychiatric problems (see psychiatric hospital), certain disease categories, and so forth.
A hospital may be a single building or a campus. (Many hospitals with pre-20th-century origins began as one building and evolved into campuses.) Some hospitals are affiliated with universities for medical research and the training of medical personnel. Worldwide, most hospitals are run on a non-profit basis by governments or charities. Within the United States, most hospitals are not-for-profit.
## Teaching
A teaching hospital (or university hospital) is that who combines assistance to patients with teaching to medical students.
## Clinics
A medical facility smaller than a hospital is called a clinic, and is often run by a government agency for health services or a private partnership of physicians (in nations where private practice is allowed). Clinics generally provide only outpatient services.
# Departments
Template:Seealso
Hospitals may have any of the following departments or units:
- Behavioral Health Services
- Burn unit
- Cancer Center
- Coronary care unit
- Dispensary
- Emergency department
- Intensive Care Unit
Neonatal intensive care unit
Trauma center
- Neonatal intensive care unit
- Trauma center
- Labor and Delivery
- Laboratory Services
- Nursing unit
- Orthopedic Services
- Outpatient Department
- Pharmacy
- Psychiatric ward
- Rehabilitation Services
- Physical Therapy
- Post anesthesia care unit
- Radiology
- Respiratory Therapy
- Surgery
- Urgent care
Non-medical departments include:
- Medical records department
- Release of Information department
# History
In ancient cultures, religion and medicine were linked. The earliest known institutions aiming to provide cure were Egyptian temples. Greek temples dedicated to the healer-god Asclepius might admit the sick, who would wait for guidance from the god in a dream. The Romans adopted his worship. Under his Roman name Æsculapius, he was provided with a temple (291 BC) on an island in the Tiber in Rome, where similar rites were performed.[1]
## Ancient Asia
The Sinhalese (Sri Lankans) are perhaps responsible for introducing the concept of dedicated hospitals to the world. According to the Mahavamsa, the ancient chronicle of Sinhalese royalty written in the 6th century A.D., King Pandukabhaya (4th century BC) had lying-in-homes and hospitals (Sivikasotthi-Sala) built in various parts of the country. This is the earliest documentary evidence we have of institutions specifically dedicated to the care of the sick anywhere in the world.[2][3] Mihintale Hospital is perhaps the oldest in the world.[4]
Institutions created specifically to care for the ill also appeared early in India. King Ashoka is said to have founded at least 18 hospitals ca. 230 BC, with physicians and nursing staff, the expense being borne by the royal treasury.[5] However, there are historians who strictly dispute the claim that Ashoka built any hospitals at all, and argue that it is based on a mistranslation, with references to 'rest houses' being mistaken for hospitals. The error is thought to have occurred because similar edicts and records talk of Ashoka importing medicinal supplies.[6]
State-supported hospitals later appeared in China during the first millennium A.D. The first teaching hospital where students were authorized to methodically practice on patients under the supervision of physicians as part of their education, was the Academy of Gundishapur in the Persian Empire. One expert has argued that "to a very large extent, the credit for the whole hospital system must be given to Persia".[7]
## Roman Empire
The Romans created valetudinaria for the care of sick slaves, gladiators and soldiers around 100 BC, and many were identified by later archeology. While their existence is considered proven, there is some doubt as to whether they were as widespread as was once thought, as many were identified only according to the layout of building remains, and not by means of surviving records or finds of medical tools.[8]
The adoption of Christianity as the state religion of the empire drove an expansion of the provision of care. The First Council of Nicaea in 325 A.D. urged the Church to provide for the poor, sick, widows and strangers. It ordered the construction of a hospital in every cathedral town. Among the earliest were those built by the physician Saint Sampson in Constantinople and by Basil, bishop of Caesarea. The latter was attached to a monastery and provided lodgings for poor and travelers, as well as treating the sick and infirm. There was a separate section for lepers.[9]
## Medieval Islam
The earliest recorded hospitals in the medieval Islamic world refer to the hopital of al-Walid ibn 'Abdul Malik (ruled 705-715 CE) which he built in 86 AH (706-707 CE). It somewhat resembled the Byzantine nosocomia, but was more general as it extended its services to the lepers and the invalid and destitute people. All treatment and care was free of charge and there was more than one physician employed in this hospital.[10]
In the medieval Islamic world, the word "Bimaristan" was used to indicate a hospital in the modern sense, an establishment where the ill were welcomed and cared for by qualified staff. In this way, Muslim physicians were the first to make a distinction between a hospital and other different forms of healing temples, sleep temples, hospices, assylums, lazarets and leper-houses, all of which in ancient times were more concerned with isolating the sick and the mad from society "rather than to offer them any way to a true cure." Some thus consider the medieval Bimaristan hospitals as "the first hospitals" in the modern sense of the word.[11] The first public hospitals,[12] psychiatric hospitals[13] and medical universities[14] were also introduced by medieval Muslim physicians.
Between the eighth and twelfth centuries CE Muslim hospitals developed a high standard of care. Hospitals built in Baghdad in the ninth and tenth centuries employed up to twenty-five staff physicians and had separate wards for different conditions. Al-Qairawan hospital and mosque, in Tunisia, were built under the Aghlabid rule in 830 CE and was simple but adequately equipped with halls organized into waiting rooms, a mosque, and a special bath. The hospital employed female nurses, including nurses from Sudan, a sign of great breakthrough. In addition to regular physicians who attended the sick, there were Fuqaha al-Badan, a kind of religious physio-therapists, group of religious scholars whose medical services included bloodletting, bone setting, and cauterisation. During Ottoman rule, when hospitals reached a particular distinction, Sultan Bayazid II built a mental hospital and medical madrasa in Edirne, and a number of other early hospitals were also built in Turkey. Unlike in Greek temples to healing gods, the clerics working in these facilities employed scientific methodology far beyond that of their contemporaries in their treatment of patients.[15]
According to Sir John Bagot Glubb:
"By Mamun's time medical schools were extremely active in Baghdad. The first free public hospital was opened in Baghdad during the Caliphate of Haroon-ar-Rashid. As the system developed, physicians and surgeons were appointed who gave lectures to medical students and issued diplomas to those who were considered qualified to practice. The first hospital in Egypt was opened in 872 AD and thereafter public hospitals sprang up all over the empire from Spain and the Maghrib to Persia."[14]
## Medieval Europe
Medieval hospitals in Europe followed a similar pattern. They were religious communities, with care provided by monks and nuns. (An old French term for hospital is hôtel-Dieu, "hostel of God.") Some were attached to monasteries; others were independent and had their own endowments, usually of property, which provided income for their support. Some hospitals were multi-function while others were founded for specific purposes such as leper hospitals, or as refuges for the poor or for pilgrims: not all cared for the sick. Not until later where most hospitals multi-functional, though the first Spanish hospital, founded by the Catholic Visigoth bishop Masona in 580 at Mérida, was a xenodochium designed as an inn for travellers (mostly pilgrims to the shrine of Eulalia of Mérida) as well as a hospital for citizens and local farmers. The hospital's endowment consisted of farms to feed its patients and guests.
## Colonial America
It is believed that the first Spanish style hospital founded in the Americas following Columbus arrival to the island now known as Hispaniola was the Hospital San Nicolás de Bari Calle Hostos in Santo Domingo, Distrito Nacional Dominican Republic.
Fray Nicolas de Ovando, Spanish governor and colonial administrator from 1502-1509, authorized its construction in or after 1504. It is believed that this hospital also served as a church during its lifetime. The first phase of its construction was completed in 1519. Erwin Walter Palm, [former author and professor of Spanish American art, culture, and history] wrote that "the Brotherhood of Our Lady of the Conception continued the construction of the hospital in 1533, adding modern elements, including additional buildings." Abandoned in the mid-18th century the hospital now lies in ruins near the Cathedral in the colonial zone in Santo Domingo, DR, amid additional historical New World sights.
The Hospital de Jesús Nazareno in Mexico City is the oldest hospital in North America. It was founded in 1524 with the economic support of conquistador Hernán Cortés to care for poor Spanish soldiers and the native inhabitants.
The first hospital in North America north of Mexico is the Hôtel-Dieu de Québec. It was established in New France in 1639 by three Augustinians from l'Hôtel-Dieu de Dieppe in France. The project of the niece of Cardinal de Richelieu was granted a royal charter by King Louis XIII and staffed by colonial physician Robert Giffard de Moncel.
## Modern era
In Europe the medieval concept of Christian care evolved during the sixteenth and seventeenth centuries into a secular one, but it was in the eighteenth century that the modern hospital began to appear, serving only medical needs and staffed with physicians and surgeons. The Charité (founded in Berlin in 1710) is an early example.
Guy's Hospital was founded in London in 1724 from a bequest by wealthy merchant Thomas Guy. Other hospitals sprang up in London and other British cities over the century, many paid for by private subscriptions. In the British American colonies the Pennsylvania General Hospital was chartered in Philadelphia in 1751, after £2,000 from private subscription was matched by funds from the Assembly.[16]
When the Viennese General Hospital (Allgemeines Krankenhaus) opened in 1784 (instantly becoming the world's largest hospital), physicians acquired a new facility that gradually developed into the most important research center. During the 19th century, the Second Viennese Medical School emerged with the contributions of physicians such as Carl Freiherr von Rokitansky, Josef Škoda, Ferdinand Ritter von Hebra and Ignaz Philipp Semmelweis. Basic medical science expanded and specialization advanced. Furthermore, the first dermatology, eye, as well as ear, nose and throat clinics in the world were founded in Vienna, being considered was the birth of specialized medicine.[citation needed]
By the mid-nineteenth century most of Europe and the United States had established a variety of public and private hospital systems. In Continental Europe the new hospitals were generally built and run from public funds. The National Health Service, the principle provider of healthcare in the United Kingdom, was founded in 1948.
In the United States the traditional hospital is a non-profit hospital, usually sponsored by a religious denomination. One of the earliest of these "almshouses" in what would become the United States was started by William Penn in Philadelphia in 1713. These hospitals are tax-exempt due to their charitable purpose, but provide only a minimum of charitable medical care. They are supplemented by large public hospitals in major cities and research hospitals often affiliated with a medical school. In the late twentieth century, chains of for-profit hospitals arose in the USA.
# Criticism
While hospitals, by concentrating equipment, skilled staff and other resources in one place, clearly provide important help to patients with serious or rare health problems, hospitals are also criticised for a number of faults, some of which are endemic to the system, others which develop from what some consider wrong approaches to health care.
One cricitism often voiced is the 'industrialised' nature of care, with constantly shifting treatment staff, which dehumanises the patient and prevents more effective care as doctors and nurses are rarely intimately familiar with the patient. The high working pressures often put on the staff exacerbates such rushed and impersonal treatment. The architecture and setup of modern hospitals is often voiced as a contributing factor to the feelings of faceless treatment many people complain about.[17]
Another criticism is that hospitals are in themselves a dangerous place for patients, which are often suffering from weakened immune systems - either due to their body having to undergo substantial surgery or because of the illness which placed them in the hospital itself. As an example, it is estimated that as much as 10% of all patients in the United States contract a nosocomical (hospital-caused) infection.[18] Due to the environment in which antibiotics are used in large quantities, the infections are also often multi-resistant to various treatment methods, such as the relatively common MRSA infection.
# Funding
In the modern era, hospitals are, broadly, either funded by the government of the country in which they are situated, or survive financially by competing in the private sector (a number of hospitals are also still supported by the historical type of charitable or religious associations).
In the United Kingdom for example, a relatively comprehensive, "free at the point of delivery" healthcare system exists, funded by the state. Hospital care is thus relatively easily available to all legal residents (although as hospitals prioritize their limited resources, there is a tendency for 'waiting lists' to be generated for non-emergency treatment, and those who can afford it may take out private healthcare to get treatment faster).[19] On the other hand, many countries, including for example the USA, have in the 20th Century followed a largely private-based, for-profit-approach to providing hospital care, with few state-money supported "charity" hospitals remaining today.[20] Where for-profit hospitals in such countries admit uninsured patients in emergency situations (such as during and after the Hurricane Katrina in the USA), they incur direct financial losses,[20] ensuring that there is a clear disincentive to admit such patients.
While for-profit-based systems have produced some of the best hospitals in the world, a proportion of the populace may have little or no access to healthcare services of adequate quality.[citation needed]
As quality of healthcare has increasingly become an issue around the world, hospitals have increasingly had to pay serious attention to this. Independent external assessment of quality is one of the most powerful ways of assessing the quality of healthcare, and hospital accreditation is one means by which this is achieved. In many parts of the world such accreditation is sourced from other countries, a phenomenon known as international healthcare accreditation, by groups such as the Joint Commission from the USA and the Trent Accreditation Scheme from Great Britain.
# Buildings
## Architecture
Modern hospital buildings are designed to minimize the effort of medical personnel and the possibility of contamination while maximizing the efficiency of the whole system. Travel time for personnel within the hospital and the transportation of patients between units is facilitated and minimized. The building also should be built to accommodate heavy departments such as radiology and operating rooms; while space for special wiring, plumbing and waste disposal must be allowed for in the design.
However, the reality is that many hospitals, even those considered 'modern', are the product of continual, and often badly managed growth over decades or even centuries, with utilitarian new sections added on as needs and finances dictate. As a result, Dutch architectural historian Cor Wagenaar has called many hospitals:
Some newer hospital designs now try to reestablish design that takes the patient's psychological needs into account, such as providing for more air, better views and more pleasant color schemes. These ideas harken back to the late 18th century, when the concept of providing fresh air and access to the 'healing powers of nature' were first employed by hospital architects in improving their buildings.[21]
Another major change which is still ongoing in many parts of the world is the change from a ward-based system (where patients are treated and accommodated in communal rooms, separated at best by movable partititions) to a room-based environment, where patients are accommodated in private rooms. The ward-based system has been described as very efficient, especially for the medical staff, but is considered to be more stressful for patients and detrimental to their privacy. A major constraint on providing all patients with their own rooms is however found in the higher cost of building and operating such a hospital, which causes some hospitals to charge for the privilege of private rooms.[22]
## Infrastructure
The surgical, special procedures, radiological, intensive care unit, and patient rooms typically have medical gases, emergency and normal electrical power; and heating, air conditioning and ventilation systems.
## Electrical
The reliability of the electrical power systems that serve a hospital is important. In order to provide higher electrical reliability, the National Institutes of Health, NIH, requires that all secondary substations > 500 kVA at their Bethesda, MD campus be the spot network type. The spot network substations cost more than other arrangements.
## Information
Pneumatic tube conveying systems are often used to move the actual paper prescriptions for medicines to the Pharmacies, and to move medicines, especially intra-venous, IV, bags to the patient care rooms. Tissue samples can be sent to the Laboratory. Medical notes can be transcribed, printed, and then transported via a Pneumatic Tube Conveying System.
As measured by the weight of the item be transferred, the 15 cm (6”) diameter tube systems have about 225% of the lifting and moving capacity of a 10 cm (4”) system. When the seals are new, the 10 cm tube carriers will move a 1 kg (2+ pound) IV bag. But when the seals on the tube carriers are worn, the tubes can stop moving in the piping, and require a trained technician to recover the tube carrier.
Modern hospitals have information infrastructure such as secured patient information system and PACS.
# References & Notes
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), pp.134-5.
- ↑ Prof. Arjuna Aluvihare, "Rohal Kramaya Lovata Dhayadha Kale Sri Lankikayo" Vidhusara Science Magazine, Nov. 1993.
- ↑ Resource Mobilization in Sri Lanka's Health Sector - Rannan-Eliya, Ravi P. & De Mel, Nishan, Harvard School of Public Health & Health Policy Programme, Institute of Policy Studies, February 1997, Page 19. Accessed 2008-02-22.
- ↑ Heinz E Müller-Dietz, Historia Hospitalium (1975).
- ↑ Encyclopedia of Medical History - McGrew, Roderick E. (Macmillan 1985), p.135.
- ↑ The Nurses should be able to Sing and Play Instruments - Wujastyk, Dominik; University College London. Accessed 2008-02-22.)
- ↑ C. Elgood, A Medical History of Persia, (Cambridge Univ. Press), p. 173.
- ↑ The Roman military Valetudinaria: fact or fiction - Baker, Patricia Anne, University of Newcastle upon Tyne, Sunday 20 December 1998
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), p.135.
- ↑ al-Hassani, Woodcock and Saoud (2007), 'Muslim heritage in Our World', FSTC Publishing, pp.154-156
- ↑ Micheau, Francoise, "The Scientific Institutions in the Medieval Near East", pp. 991–2 Missing or empty |title= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}, in Template:Harv
- ↑ Peter Barrett (2004), Science and Theology Since Copernicus: The Search for Understanding, p. 18, Continuum International Publishing Group, ISBN 056708969X.
- ↑ Ibrahim B. Syed PhD, "Islamic Medicine: 1000 years ahead of its times", Journal of the Islamic Medical Association, 2002 (2), p. 2-9 [7-8].
- ↑ Jump up to: 14.0 14.1 Sir Glubb, John Bagot (1969), A Short History of the Arab Peoples, retrieved 2008-01-25
- ↑ Turkish Contributions to Scientific Work in Islam - Sayili, Aydin, Foundation For Science, Technology and Civilisation, Septermber 2004, Page 9
- ↑ Roderick E. McGrew, Encyclopedia of Medical History (Macmillan 1985), p.139.
- ↑ References provided in this same article.
- ↑ References provided in the linked article.
- ↑ Surgery worries create insurance boom – The New Zealand Herald, Monday 21 January 2008
- ↑ Jump up to: 20.0 20.1 Hospitals in New Orleans see surge in uninsured patients but not public funds – USA Today, Wednesday 26 April 2006
- ↑ Jump up to: 21.0 21.1 Healing by design – Ode Magazine, July/August 2006 issue. Accessed 2008-02-10.
- ↑ Health administrators go shopping for new hospital designs – National Review of Medicine, Monday 15 November 2004, Volume 1 NO. 21
- Template:Harvard reference
# External links
- Jean Manco, The Heritage of Mercy (medieval hospitals in Britain)
- Last Resort: Hospital Care in Canada (an illustrated historical essay)
- Medieval Hospitals of England, by Rotha Mary Clay (1909 book, now in the public domain)
- Hospital Metrics and Scorecard
ar:مستشفى
az:Qospital
bg:Болница
ceb:Ospital
cs:Nemocnice
cv:Пульница
da:Hospital
de:Krankenhaus
el:Νοσοκομείο
eo:Malsanulejo
et:Haigla
fa:بیمارستان
fi:Sairaala
he:בית חולים
hr:Bolnica
id:Rumah sakit
it:Ospedale
iu:ᐋᓐᓂᐊᕐᕕᒃ/aanniarvik
ko:병원
la:Valetudinarium
ln:Ndáko ya bokɔnɔ
lt:Ligoninė
mg:Hopitaly
mk:Болница
ms:Hospital
nl:Ziekenhuis
nn:Sjukehus
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Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Dispensaries | |
aee6472c02568ca39e0b8b2f11945003aa277e28 | wikidoc | Thiazide | Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretic.
The members of these diuretics are derived from benzothiadiazine. They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl- symporter. Thiazides also cause loss of potassium and an increase in serum uric acid. The chemical structure of the original thiazide diuretics contained a thiazide ring system; the term is also used for drugs with a similar action that are not chemically thiazides, such as chlortalidone and metolazone.
# Denomination
That thiazide both refers to the type of molecule and the medication can sometimes lead to confusion, because some molecules can be considered thiazide diuretics, although they are not thiazides from a chemical perspective. In this context, "thiazide" refers to a drug which acts at a "thiazide receptor", which is believed to be a sodium-chloride symporter.
# Primary uses
Because of their vasodilator properties, Thiazides are often used to treat hypertension. They are the recommended first-line treatment in the US (JNC VII) guidelines and a recommended treatment in the European (ESC/ESH) guidelines. They have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by desensitizing the vascular smooth muscle cells to calcium release induced by norepinephrine.
Among the thiazides and thiazide-like diurectics, chlorthalidone may be more effective for hypertension control than hydrochlorothiazide.
# Side effects
Side effects can include hypokalemia, increased serum cholesterol, and impotence. The side effect of hypokalemia has motivated combining thiazides with potassium sparing diuretics (eg with amiloride in co-amilozide) and with the newer ACE inhibitors, which also lower blood pressure but cause hyperkalemia as a side effect.
Long-term usage of thiazides is also linked to increased levels of homocysteine, a toxic amino acid byproduct, that has been associated with atherosclerosis. It is recommended that patients receiving long-term thiazide treatments also receive folic acid supplements to combat the risk. They have been known to cause a paradoxical effect in Diabetes insipidus, where they reduce the volume of urine. Thiazide diuretics are capable of inhibiting urate secretions.
About 3% of the population will have an allergic reaction to a thiazide. Signs and symptoms of an allergic reaction include a rash(either eczematous reaction with red itchy scaly skin and crusting or erythema anular centrifugum), hives, itching, nasal congestion, shortness of breath, wheezing, tachycardia, cough, nausea or diarrhea. Anaphylactic reactions with hypotension, angioedema and a leukocytoclastic vasculitis are rare.
## Thiazide-induced hyponatremia
"Fractional uric acid clearance was elevated and serum uric acid levels were low. These results are consistent with excess ADH activity as having caused hyponatraemia induced by thiazides in cases".
## Epidemiology
Over 5 years of treatment, one in 15 patients treated with thiazides may have a low sodium value (sodium≤130 mmol/L) and a mean of 1.75 years after treatment started.
However, a more recent report by Kaiser, who also published that a hypertension clinical practice guideline that is based on a thiazide-angiotensin converting enzyme inhibitor combination, has great improved hypertension control over a large population and that their decline and cardiovascular mortality exceeds the national decline, found 1.4% per year rate of hyponatremia among patients treated with the combination pill.
Predictors include baseline hyponatremia (sodium < 140 mEq/L)
Hypokalemia at baseline may be a better predictor than hyonatremia at baseline.
## Practice gaps
In 18% of patients on thiazides the sodium was not monitored over the course of study and in another study, 42% were not montiored in the first 90 days. Other studies have found gaps.
In half of cases where a sodium less than 130 is found, the diuretic is not stopped.
### Diagnosis
Fractional uric acid clearance is elevated and serum uric acid levels are low..
If the FEurate is normal (4 to 11%), this suggests psychogenic polydipsia or reset osmostat.
### Treatment
Various studies of have compared loop diurectics, including furosemide, with thiazide diuretics as they have opposite handling of sodium in the kidney. Trial have been summarized in a systematic review by the Cochrane Collaboration.
Potassium replacement may help.
# Other uses
Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones. This effect is associated with positive calcium balance and is associated with an increase in bone mineral density and reductions in fracture rates attributable to osteoporosis. Because of those properties, they are also used in the treatment of Dent's Disease or idiopathic hypercalciuria.
Thiazide may be combined with ACE inhibitors to increase diuresis without changing plasma potassium concentrations. While ACE inhibitors cause diuresis with potassium retention, thiazide increases potassium excretion. Their combined effects on potassium cancel each other out.
# Breast milk
It should be noted that thiazides pass through breast milk, and in some cases, decrease the flow of breast milk. There is no specific information regarding the use of thiazides in children, but it is still advised that mothers avoid using thiazides during the first month of breast feeding.
# Mechanisms of hypokalemia
There are several mechanisms by which thiazide diuretics cause hypokalaemia (decreased plasma potassium concentration):
- Increased delivery of sodium to the collecting ducts causes the Na/K exchanger to be activated resulting in K (and H+) loss.
- Activation of renin-angiotensin-aldosterone system by the diuretic hypovolaemia: body responds to hypovolaemia by opposing diuresis, one effect of which is to produce aldosterone which stimulates the Na/K exchanger, resulting in further loss of potassium. For this reason, ACE inhibitors, which inhibit angiotensin II production and therefore aldosterone activation, are frequently used in combination with thiazides to combat hypokalaemia.
- Flow rate in nephron is increased under diuresis, reducing potassium concentration in the lumen, thus increasing the potassium gradient. Potassium loss through the many potassium channels, such as ROMK. These are not exchangers; they allow facilitated diffusion, so the increased gradient is directly responsible for increased diffusion.
Thiazides overuse must be differentiated from other causes of hypercalcaemia | Thiazide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Thiazide is a term used to describe a type of molecule[1] and a class of diuretic.[2]
The members of these diuretics are derived from benzothiadiazine. They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl- symporter. Thiazides also cause loss of potassium and an increase in serum uric acid. The chemical structure of the original thiazide diuretics contained a thiazide ring system; the term is also used for drugs with a similar action that are not chemically thiazides, such as chlortalidone and metolazone.
# Denomination
That thiazide both refers to the type of molecule and the medication can sometimes lead to confusion, because some molecules can be considered thiazide diuretics, although they are not thiazides from a chemical perspective. In this context, "thiazide" refers to a drug which acts at a "thiazide receptor"[3], which is believed to be a sodium-chloride symporter.
# Primary uses
Because of their vasodilator properties, Thiazides are often used to treat hypertension. They are the recommended first-line treatment in the US (JNC VII)[4] guidelines and a recommended treatment in the European (ESC/ESH)[5] guidelines. They have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by desensitizing the vascular smooth muscle cells to calcium release induced by norepinephrine.[6]
Among the thiazides and thiazide-like diurectics, chlorthalidone may be more effective for hypertension control than hydrochlorothiazide.[7]
# Side effects
Side effects can include hypokalemia, increased serum cholesterol, and impotence. The side effect of hypokalemia has motivated combining thiazides with potassium sparing diuretics (eg with amiloride in co-amilozide) and with the newer ACE inhibitors, which also lower blood pressure but cause hyperkalemia as a side effect.
Long-term usage of thiazides is also linked to increased levels of homocysteine, a toxic amino acid byproduct, that has been associated with atherosclerosis. It is recommended that patients receiving long-term thiazide treatments also receive folic acid supplements to combat the risk. They have been known to cause a paradoxical effect in Diabetes insipidus, where they reduce the volume of urine. Thiazide diuretics are capable of inhibiting urate secretions.
About 3% of the population will have an allergic reaction to a thiazide. Signs and symptoms of an allergic reaction include a rash(either eczematous reaction with red itchy scaly skin and crusting or erythema anular centrifugum), hives, itching, nasal congestion, shortness of breath, wheezing, tachycardia, cough, nausea or diarrhea. Anaphylactic reactions with hypotension, angioedema and a leukocytoclastic vasculitis are rare.
## Thiazide-induced hyponatremia
"Fractional uric acid clearance was elevated and serum uric acid levels were low. These results are consistent with excess ADH activity as having caused hyponatraemia induced by thiazides in [most] cases"[8].
## Epidemiology
Over 5 years of treatment, one in 15 patients treated with thiazides may have a low sodium value (sodium≤130 mmol/L) and a mean of 1.75 years after treatment started[9].
However, a more recent report by Kaiser, who also published that a hypertension clinical practice guideline that is based on a thiazide-angiotensin converting enzyme inhibitor combination, has great improved hypertension control over a large population[10] and that their decline and cardiovascular mortality exceeds the national decline[11], found 1.4% per year rate of hyponatremia among patients treated with the combination pill[12].
Predictors include baseline hyponatremia (sodium < 140 mEq/L)[13]
Hypokalemia at baseline may be a better predictor than hyonatremia at baseline[14].
## Practice gaps
In 18% of patients on thiazides the sodium was not monitored[9] over the course of study and in another study, 42% were not montiored in the first 90 days[13]. Other studies have found gaps[15].
In half of cases where a sodium less than 130 is found, the diuretic is not stopped[16].
### Diagnosis
Fractional uric acid clearance is elevated and serum uric acid levels are low.[8].
If the FEurate is normal (4 to 11%), this suggests psychogenic polydipsia or reset osmostat[17].
### Treatment
Various studies of have compared loop diurectics, including furosemide, with thiazide diuretics as they have opposite handling of sodium in the kidney[18][19]. Trial have been summarized in a systematic review by the Cochrane Collaboration[20].
Potassium replacement may help[21].
# Other uses
Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones. This effect is associated with positive calcium balance and is associated with an increase in bone mineral density and reductions in fracture rates attributable to osteoporosis. Because of those properties, they are also used in the treatment of Dent's Disease or idiopathic hypercalciuria.
Thiazide may be combined with ACE inhibitors to increase diuresis without changing plasma potassium concentrations. While ACE inhibitors cause diuresis with potassium retention, thiazide increases potassium excretion. Their combined effects on potassium cancel each other out.
# Breast milk
It should be noted that thiazides pass through breast milk, and in some cases, decrease the flow of breast milk. There is no specific information regarding the use of thiazides in children, but it is still advised that mothers avoid using thiazides during the first month of breast feeding.
# Mechanisms of hypokalemia
There are several mechanisms by which thiazide diuretics cause hypokalaemia (decreased plasma potassium concentration):
- Increased delivery of sodium to the collecting ducts causes the Na/K exchanger to be activated resulting in K (and H+) loss.
- Activation of renin-angiotensin-aldosterone system by the diuretic hypovolaemia: body responds to hypovolaemia by opposing diuresis, one effect of which is to produce aldosterone which stimulates the Na/K exchanger, resulting in further loss of potassium. For this reason, ACE inhibitors, which inhibit angiotensin II production and therefore aldosterone activation, are frequently used in combination with thiazides to combat hypokalaemia.
- Flow rate in nephron is increased under diuresis, reducing potassium concentration in the lumen, thus increasing the potassium gradient. Potassium loss through the many potassium channels, such as ROMK. These are not exchangers; they allow facilitated diffusion, so the increased gradient is directly responsible for increased diffusion.
Thiazides overuse must be differentiated from other causes of hypercalcaemia | https://www.wikidoc.org/index.php/Diucardin | |
03c3e2a759b10317b49dccf18f4188d0a4365dc9 | wikidoc | Diuresis | Diuresis
# Overview
Diuresis is the increased production of urine by the kidney.
# Types and causes
The kidney normally produces up to 250 L of "pro-urine" (glomerular filtrate) per day, but reabsorbs most of this before it reaches the bladder.
Polyuria is increased diuresis. This may be due to large fluid intake, various illnesses (diabetes insipidus, osmotic diuresis due to diabetes mellitus or hypercalcemia) or various chemical substances (diuretics, caffeine, alcohol). It may also occur after supraventricular tachycardias, during an onset of atrial fibrillation, childbirth, and the removal of an obstruction within the urinary tract. Diuresis is restrained by antidiuretics such as ADH, angiotensin II and aldosterone.
Cold diuresis is the occurrence of increased urine production on exposure to cold.
Substances that increase diuresis are called diuretics. Coffee is an example of a proposed diuretic.
Substances that decrease diuresis allow more vasopressin or antidiuretic hormone (ADH) to be present in the kidney.
High-altitude diuresis occurs at altitudes above 10,000 ft and is a desirable indicator of adaptation to high altitudes. Mountaineers who are adapting well to high altitudes experience this type of diuresis. Urine output is thus an important indicator of adaptation to altitude (or lack thereof). Persons who produce less urine even in the presence of adequate fluid intake probably are not adapting well to altitude (Hackett 1980; pp. 54, 62). | Diuresis
# Overview
Diuresis is the increased production of urine by the kidney.
# Types and causes
The kidney normally produces up to 250 L of "pro-urine" (glomerular filtrate) per day, but reabsorbs most of this before it reaches the bladder.
Polyuria is increased diuresis. This may be due to large fluid intake, various illnesses (diabetes insipidus, osmotic diuresis due to diabetes mellitus or hypercalcemia) or various chemical substances (diuretics, caffeine, alcohol). It may also occur after supraventricular tachycardias, during an onset of atrial fibrillation, childbirth, and the removal of an obstruction within the urinary tract. Diuresis is restrained by antidiuretics such as ADH, angiotensin II and aldosterone.
Cold diuresis is the occurrence of increased urine production on exposure to cold.
Substances that increase diuresis are called diuretics. Coffee is an example of a proposed diuretic.
Substances that decrease diuresis allow more vasopressin or antidiuretic hormone (ADH) to be present in the kidney.
High-altitude diuresis occurs at altitudes above 10,000 ft and is a desirable indicator of adaptation to high altitudes. Mountaineers who are adapting well to high altitudes experience this type of diuresis. Urine output is thus an important indicator of adaptation to altitude (or lack thereof). Persons who produce less urine even in the presence of adequate fluid intake probably are not adapting well to altitude (Hackett 1980; pp. 54, 62). | https://www.wikidoc.org/index.php/Diuresis | |
2183f435634e81d0ec635b596483acc747f42b01 | wikidoc | Diuretic | Diuretic
# Overview
A diuretic is any drug that elevates the rate of bodily urine excretion (diuresis). There are several categories of diuretics. All diuretics increase the excretion of water from the body, although each class of diuretic does so in a distinct way.
# High ceiling loop diuretics
High ceiling diuretics are diuretics that may cause a substantial diuresis - up to 20% of the filtered load of NaCl and water. This is huge, compared to that normal renal sodium reabsorption leaves only ~0.4% of filtered sodium in the urine.
Loop diuretics have this ability, and is therefore often synonymous with high ceiling diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the kidney which leads to a retention of water in the urine as water normally follows sodium back into the extracellular fluid (ECF). Other examples of high ceiling loop diuretics include ethacrynic acid, torsemide and bumetanide.
# Thiazides
Drugs such as hydrochlorothiazide act on the distal tubule and inhibit the Na-Cl symport leading to a retention of water in the urine as water normally follows penetrating solutes.
# Potassium-sparing diuretics
These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. Such drugs include spironolactone which is a competitive antagonists of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. Other examples of potassium-sparing diuretics are amiloride and triamterene. These drugs bind to the sodium channels of the principal cells, inhibiting an aldosterone-induced increase in sodium reabsorption.
# Osmotic diuretics
Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.
## High Blood Glucose
Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is commonly found in the blood. However, in certain conditions such as diabetes mellitus, the concentration of glucose in the blood exceeds the maximum resorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Use of some drugs, especially stimulants may also increase blood glucose and thus increase urination.
# Uses
In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. Diuretics are often abused by sufferers of eating disorders, especially bulimics, in attempts at weight loss.
The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. Indapamide was specifically designed with this in mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics.
# Mechanism of action
Classification of common diuretics and their mechanisms of action:
Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. Herbal medications are not inherently diuretics. They are more correctly called aquaretics.
# Adverse effects
The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis and hyperuricemia . Each are at risk of certain types of diuretics and present with different symptoms. | Diuretic
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A diuretic is any drug that elevates the rate of bodily urine excretion (diuresis). There are several categories of diuretics. All diuretics increase the excretion of water from the body, although each class of diuretic does so in a distinct way.
# High ceiling loop diuretics
High ceiling diuretics are diuretics that may cause a substantial diuresis - up to 20%[1] of the filtered load of NaCl and water. This is huge, compared to that normal renal sodium reabsorption leaves only ~0.4% of filtered sodium in the urine.
Loop diuretics have this ability, and is therefore often synonymous with high ceiling diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the kidney which leads to a retention of water in the urine as water normally follows sodium back into the extracellular fluid (ECF). Other examples of high ceiling loop diuretics include ethacrynic acid, torsemide and bumetanide.
# Thiazides
Drugs such as hydrochlorothiazide act on the distal tubule and inhibit the Na-Cl symport leading to a retention of water in the urine as water normally follows penetrating solutes.
# Potassium-sparing diuretics
These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. Such drugs include spironolactone which is a competitive antagonists of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. Other examples of potassium-sparing diuretics are amiloride and triamterene. These drugs bind to the sodium channels of the principal cells, inhibiting an aldosterone-induced increase in sodium reabsorption.
# Osmotic diuretics
Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.
## High Blood Glucose
Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is commonly found in the blood. However, in certain conditions such as diabetes mellitus, the concentration of glucose in the blood exceeds the maximum resorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Use of some drugs, especially stimulants may also increase blood glucose and thus increase urination.
# Uses
In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. Diuretics are often abused by sufferers of eating disorders, especially bulimics, in attempts at weight loss.
The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. Indapamide was specifically designed with this in mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics.
# Mechanism of action
Classification of common diuretics and their mechanisms of action:
Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. Herbal medications are not inherently diuretics. They are more correctly called aquaretics.
# Adverse effects
The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis and hyperuricemia [2]. Each are at risk of certain types of diuretics and present with different symptoms. | https://www.wikidoc.org/index.php/Diuretic | |
2496cfa793fd42e4382425359aa539e8d20ecebc | wikidoc | Docusate | Docusate
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Docusate is a OTC Laxative that is FDA approved for the treatment of constipation. Common adverse reactions include Stomach pain, diarrhea, or cramping.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- For the relief of occasional constipation due to hard stools. The effect on stools is usually apparent 1 to 3 days after the first dose.
### Dosage
- As directed by a physician or once daily as follows: Adults and children 12 years of age and over: oral dosage is 5 to 20 mL (1 to 4 teaspoonfuls). Children 6 to under 12 years of age: oral dosage is 5 to 10 mL (1 to 2 teaspoonfuls). Children 3 to under 6 years of age: oral dosage is 2.5 to 5 mL (1⁄2 to 1 teaspoonful). Children under 3 years of age: consult a physician. The higher doses are recommended for initial therapy. Dosage should be adjusted to individual response. If desired, the product may be administered in a 6 to 8 oz glass of milk or fruit juice or in infant formula to mask the bitter taste.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Docusate in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Docusate in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
### Dosage
- As directed by a physician or once daily as follows: Adults and children 12 years of age and over: oral dosage is 5 to 20 mL (1 to 4 teaspoonfuls). Children 6 to under 12 years of age: oral dosage is 5 to 10 mL (1 to 2 teaspoonfuls). Children 3 to under 6 years of age: oral dosage is 2.5 to 5 mL (1⁄2 to 1 teaspoonful). Children under 3 years of age: consult a physician. The higher doses are recommended for initial therapy. Dosage should be adjusted to individual response. If desired, the product may be administered in a 6 to 8 oz glass of milk or fruit juice or in infant formula to mask the bitter taste.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Docusate in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Docusate in pediatric patients.
# Contraindications
There is limited information regarding Contraindications of Docusate in the drug label.
# Warnings
- Do not use laxative products when abdominal pain, nausea, or vomiting are present, or use for a period longer than 1 week, unless directed by a physician. If you have noticed a sudden change in bowel habits that persists over a period of 2 weeks, consult a physician before using a laxative. Rectal bleeding or failure to have a bowel move- ment after the use of a laxative may indicate a serious condition. Discontinue use and consult your physician. As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product. May cause rash in some cases.
- KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.
# Adverse Reactions
## Clinical Trials Experience
Stomach pain, diarrhea, or cramping
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Docusate in the drug label.
# Drug Interactions
- Do not take this product if you are presently taking mineral oil or a prescription drug, unless directed by a physician.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Docusate in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Docusate during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Docusate with respect to nursing mothers.
### Pediatric Use
There is no FDA guidance on the use of Docusate with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Docusate with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Docusate with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Docusate with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Docusate in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Docusate in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Docusate in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Docusate in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Docusate in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Docusate in the drug label.
# Overdosage
There is limited information regarding Overdose of Docusate in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Docusate Mechanism of Action in the drug label.
## Structure
- Each 5 mL (teaspoonful) contains docusate sodium 50 mg.
- Citric acid, D&C Red No. 33, flavoring, glycerin, propylene glycol, purified water, sodium citrate, sodium saccharin, and sorbitol.
- Sodium Content: 14 mg/5 mL.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Docusate in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Docusate in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Docusate in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Docusate in the drug label.
# How Supplied
There is limited information regarding Docusate How Supplied in the drug label.
## Storage
- Keep tightly closed. Store at controlled room temperature, 20° to 25°C (68° to 77°F). Protect from freezing. Protect from light.
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
Docusate Sodium Liquid
100 mg/ 10mL
Stool Softener Laxative
5 Cups
### Ingredients and Appearance
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Docusate in the drug label.
# Precautions with Alcohol
- Alcohol-Docusate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- DOCUSATE SODIUM®
# Look-Alike Drug Names
There is limited information regarding Docusate Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Docusate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Docusate is a OTC Laxative that is FDA approved for the treatment of constipation. Common adverse reactions include Stomach pain, diarrhea, or cramping.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- For the relief of occasional constipation due to hard stools. The effect on stools is usually apparent 1 to 3 days after the first dose.
### Dosage
- As directed by a physician or once daily as follows: Adults and children 12 years of age and over: oral dosage is 5 to 20 mL (1 to 4 teaspoonfuls). Children 6 to under 12 years of age: oral dosage is 5 to 10 mL (1 to 2 teaspoonfuls). Children 3 to under 6 years of age: oral dosage is 2.5 to 5 mL (1⁄2 to 1 teaspoonful). Children under 3 years of age: consult a physician. The higher doses are recommended for initial therapy. Dosage should be adjusted to individual response. If desired, the product may be administered in a 6 to 8 oz glass of milk or fruit juice or in infant formula to mask the bitter taste.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Docusate in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Docusate in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
### Dosage
- As directed by a physician or once daily as follows: Adults and children 12 years of age and over: oral dosage is 5 to 20 mL (1 to 4 teaspoonfuls). Children 6 to under 12 years of age: oral dosage is 5 to 10 mL (1 to 2 teaspoonfuls). Children 3 to under 6 years of age: oral dosage is 2.5 to 5 mL (1⁄2 to 1 teaspoonful). Children under 3 years of age: consult a physician. The higher doses are recommended for initial therapy. Dosage should be adjusted to individual response. If desired, the product may be administered in a 6 to 8 oz glass of milk or fruit juice or in infant formula to mask the bitter taste.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Docusate in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Docusate in pediatric patients.
# Contraindications
There is limited information regarding Contraindications of Docusate in the drug label.
# Warnings
- Do not use laxative products when abdominal pain, nausea, or vomiting are present, or use for a period longer than 1 week, unless directed by a physician. If you have noticed a sudden change in bowel habits that persists over a period of 2 weeks, consult a physician before using a laxative. Rectal bleeding or failure to have a bowel move- ment after the use of a laxative may indicate a serious condition. Discontinue use and consult your physician. As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product. May cause rash in some cases.
- KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.
# Adverse Reactions
## Clinical Trials Experience
Stomach pain, diarrhea, or cramping
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Docusate in the drug label.
# Drug Interactions
- Do not take this product if you are presently taking mineral oil or a prescription drug, unless directed by a physician.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Docusate in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Docusate during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Docusate with respect to nursing mothers.
### Pediatric Use
There is no FDA guidance on the use of Docusate with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Docusate with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Docusate with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Docusate with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Docusate in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Docusate in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Docusate in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Docusate in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Docusate in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Docusate in the drug label.
# Overdosage
There is limited information regarding Overdose of Docusate in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Docusate Mechanism of Action in the drug label.
## Structure
- Each 5 mL (teaspoonful) contains docusate sodium 50 mg.
- Citric acid, D&C Red No. 33, flavoring, glycerin, propylene glycol, purified water, sodium citrate, sodium saccharin, and sorbitol.
- Sodium Content: 14 mg/5 mL.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Docusate in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Docusate in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Docusate in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Docusate in the drug label.
# How Supplied
There is limited information regarding Docusate How Supplied in the drug label.
## Storage
- Keep tightly closed. Store at controlled room temperature, 20° to 25°C (68° to 77°F). Protect from freezing. Protect from light.
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
Docusate Sodium Liquid
100 mg/ 10mL
Stool Softener Laxative
5 Cups
### Ingredients and Appearance
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Docusate in the drug label.
# Precautions with Alcohol
- Alcohol-Docusate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- DOCUSATE SODIUM®[1]
# Look-Alike Drug Names
There is limited information regarding Docusate Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Docusate | |
959431e87450b1ff1676418393a740b116ad69ad | wikidoc | Doenjang | Doenjang
Doenjang is a traditional Korean fermented soybean paste. Beans are boiled and ground by rock into fine bits and formed into a block, which is called meju (메주). The blocks are then exposed to sunlight to be dried, during which mold special to soybean appears and the initial fermentation process begins. This sometimes produces an unpleasant fish-like smell. After the blocks have been dried, they are put in a warmer place to speed up the fermentation. Still later, they are put into large opaque pottery jars with brine and left to further fermentation, during which time various beneficial bacteria transform the mixture into a further vitamin-enriched substance, similar to the way milk ferments to become yogurt. Liquids and solids are separated after the fermentation process, and the liquid becomes Korean soy sauce (Joseon ganjang; 조선간장). The solid, which is doenjang, is very salty and quite thick, often containing (unlike most miso) some whole, uncrushed soybeans.
While traditional homemade doenjang is made with soybeans and brine only, many factory-made variants of doenjang contain a fair amount of wheat flour just like most of factory-made soy sauce does. Some current makers also add fermented, dried and ground anchovies to intensify doenjang's savor.
Doenjang can be eaten as a condiment in raw paste-form with vegetables, similar to the way some people dip celery into cheese, but it is more commonly mixed with garlic, sesame oil, and sometimes gochujang to produce ssamjang (also known as tum yum paste in Houston, TX) which is then traditionally eaten with or without rice wrapped in leaf vegetables such as Chinese cabbage. This dish is called ssambap.
It can also be used as a component of soup broth, for example in a popular stew (jjigae) called doenjang jjigae which usually includes tofu, various vegetables such as chile peppers, zucchini and welsh onion, and (optionally) mushrooms, red meat, or scallops.
Doenjang is rich in flavonoids and beneficial vitamins, minerals, and hormones which are sometimes claimed to possess anti-carcinogenic properties. | Doenjang
Template:Infobox Korean name
Doenjang is a traditional Korean fermented soybean paste. Beans are boiled and ground by rock into fine bits and formed into a block, which is called meju (메주). The blocks are then exposed to sunlight to be dried, during which mold special to soybean appears and the initial fermentation process begins. This sometimes produces an unpleasant fish-like smell. After the blocks have been dried, they are put in a warmer place to speed up the fermentation. Still later, they are put into large opaque pottery jars with brine and left to further fermentation, during which time various beneficial bacteria transform the mixture into a further vitamin-enriched substance, similar to the way milk ferments to become yogurt. Liquids and solids are separated after the fermentation process, and the liquid becomes Korean soy sauce (Joseon ganjang; 조선간장). The solid, which is doenjang, is very salty and quite thick, often containing (unlike most miso) some whole, uncrushed soybeans.
While traditional homemade doenjang is made with soybeans and brine only, many factory-made variants of doenjang contain a fair amount of wheat flour just like most of factory-made soy sauce does. Some current makers also add fermented, dried and ground anchovies to intensify doenjang's savor.
Doenjang can be eaten as a condiment in raw paste-form with vegetables, similar to the way some people dip celery into cheese, but it is more commonly mixed with garlic, sesame oil, and sometimes gochujang to produce ssamjang (also known as tum yum paste in Houston, TX) which is then traditionally eaten with or without rice wrapped in leaf vegetables such as Chinese cabbage. This dish is called ssambap.
It can also be used as a component of soup broth, for example in a popular stew (jjigae) called doenjang jjigae which usually includes tofu, various vegetables such as chile peppers, zucchini and welsh onion, and (optionally) mushrooms, red meat, or scallops.
Doenjang is rich in flavonoids and beneficial vitamins, minerals, and hormones which are sometimes claimed to possess anti-carcinogenic properties. | https://www.wikidoc.org/index.php/Doenjang | |
a9e29fa5c387d4eb588ad2ec27aa2f251b16ca15 | wikidoc | Dopamine | Dopamine
# Overview
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area. Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.
Dopamine is available as an intravenous medication acting on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, because dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and dopa-responsive dystonia, L-DOPA, which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.
# History
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England. It was named dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine (L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden. Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but a neurotransmitter as well.
# Biochemistry
## Name and family
Dopamine has the chemical formula C6H3(OH)2-CH2-CH2-NH2. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol" and its abbreviation is "DA."
As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline) in the biosynthetic pathways for these neurotransmitters.
## Biosynthesis
Dopamine is biosynthesized in the body (mainly by nervous tissue and the medulla of the adrenal glands) first by the hydroxylation of the amino acid L-tyrosine to L-DOPA via the enzyme tyrosine 3-monooxygenase, also known as tyrosine hydroxylase, and then by the decarboxylation of L-DOPA by aromatic L-amino acid decarboxylase (which is often referred to as dopa decarboxylase). In some neurons, dopamine is further processed into norepinephrine by dopamine beta-hydroxylase.
In neurons, dopamine is packaged after synthesis into vesicles, which are then released into the synapse in response to a presynaptic action potential.
## Inactivation and degradation
Two major degradation pathways for dopamine exist. In most areas of the brain, including the striatum and basal ganglia, dopamine is inactivated by reuptake via the dopamine transporter (DAT1), then enzymatic breakdown by monoamine oxidase (MAOA and MAOB) into 3,4-dihydroxyphenylacetic acid. In the prefrontal cortex, however, there are very few dopamine transporter proteins, and dopamine is instead inactivated by reuptake via the norepinephrine transporter (NET), presumably on neighboring norepinephrine neurons, then enzymatic breakdown by catechol-O-methyl transferase (COMT) into 3-methoxytyramine. The DAT1 pathway is roughly an order of magnitude faster than the NET pathway: in mice, dopamine concentrations decay with a half-life of 200 ms in the caudate nucleus (which uses the DAT1 pathway) versus 2,000 ms in the prefrontal cortex. Dopamine that is not broken down by enzymes is repackaged into vesicles for reuse by VMAT2.
# Functions in the brain
Dopamine has many functions in the brain, including important roles in behavior and cognition, voluntary movement, motivation, punishment and reward, inhibition of prolactin production (involved in lactation and sexual gratification), sleep, mood, attention, working memory, and learning. Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are present chiefly in the ventral tegmental area (VTA) of the midbrain, the substantia nigra pars compacta, and the arcuate nucleus of the hypothalamus.
It has been hypothesized that dopamine transmits reward prediction error, although this has been questioned. According to this hypothesis, the phasic responses of dopamine neurons are observed when an unexpected reward is presented. These responses transfer to the onset of a conditioned stimulus after repeated pairings with the reward. Further, dopamine neurons are depressed when the expected reward is omitted. Thus, dopamine neurons seem to encode the prediction error of rewarding outcomes. In nature, we learn to repeat behaviors that lead to maximizing rewards. Dopamine is therefore believed to provide a teaching signal to parts of the brain responsible for acquiring new behavior. Temporal difference learning provides a computational model describing how the prediction error of dopamine neurons is used as a teaching signal.
The reward system in insects uses octopamine, which is the presumed arthropod homolog of norepinephrine, rather than dopamine. In insects, dopamine acts instead as a punishment signal and is necessary to form aversive memories.
## Anatomy
Dopaminergic neurons form a neurotransmitter system which originates in substantia nigra pars compacta, ventral tegmental area (VTA), and hypothalamus. These project axons to large areas of the brain which are typically divided into four major pathways:
- Mesocortical pathway connects the ventral tegmental area to the frontal lobe of the pre-frontal cortex. Neurons with somas in the ventral tegmental area project axons into the pre-frontal cortex.
- Mesolimbic pathway carries dopamine from the ventral tegmental area to the nucleus accumbens via the amygdala and hippocampus. The somas of the projecting neurons are in the ventral tegmental area.
- Nigrostriatal pathway runs from the substantia nigra to the neostriatum. Somas in the substantia nigra project axons into the caudate nucleus and putamen. The pathway is involved in the basal ganglia motor loop.
- Tuberoinfundibular pathway runs from the hypothalamus to the pituitary gland.
This innervation explains many of the effects of activating this dopamine system. For instance, the mesolimbic pathway connects the VTA and nucleus accumbens; both are central to the brain reward system.
Whilst the distinction between pathways is widely used, and is regarded as a “convenient heuristic when considering the dopamine system”, it is not absolute, and there is some overlap in the projection targets of each group of neurons.
## Tonic and phasic activity
The level of extracellular dopamine is modulated by two mechanisms, tonic and phasic dopamine transmission. Tonic dopamine transmission occurs when small amounts of dopamine are released independently of neuronal activity, and is regulated by the activity of other neurons and neurotransmitter reuptake. Phasic dopamine release results from the activity of the dopamine-containing cells themselves. This activity is characterized by irregular pacemaking activity of single spikes, and rapid bursts of typically 2-6 spikes in quick succession. Concentrated bursts of activity result in a greater increase of extracellular dopamine levels than would be expected from the same number of spikes distributed over a longer period of time.
## Movement
Via the dopamine receptors, D1-5, dopamine reduces the influence of the indirect pathway, and increases the actions of the direct pathway within the basal ganglia. Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson's disease, in which a person loses the ability to execute smooth, controlled movements.
## Cognition and frontal cortex
In the frontal lobes, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive functions, especially memory, attention, and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder. It has been found that D1 receptors as well as D4 receptors are responsible for the cognitive-enhancing effects of dopamine.
## Regulating prolactin secretion
Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactin from the anterior pituitary gland. Dopamine produced by neurons in the arcuate nucleus of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the median eminence, which supply the pituitary gland. The lactotrope cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone (PIH), or prolactostatin.
## Motivation and pleasure
### Reinforcement
Dopamine is commonly associated with the reward system of the brain, providing feelings of enjoyment and reinforcement to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens and prefrontal cortex) by rewarding experiences such as food, sex, drugs, and neutral stimuli that become associated with them. Recent studies indicate that aggression may also stimulate the release of dopamine in this way.
This theory is often discussed in terms of drugs such as cocaine, nicotine, and amphetamines, which directly or indirectly lead to an increase of dopamine in the mesolimbic reward pathway of the brain, and in relation to neurobiological theories of chemical addiction (not to be confused with psychological dependence), arguing that this dopamine pathway is pathologically altered in addicted persons.
### Reuptake inhibition, expulsion
Cocaine and amphetamines inhibit the re-uptake of dopamine; however, they influence separate mechanisms of action. Cocaine is a dopamine transporter and norepinephrine transporter blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters. Like cocaine, amphetamines increase the concentration of dopamine in the synaptic gap, but by a different mechanism. Amphetamines and methamphetamine are similar in structure to dopamine, and so can enter the terminal bouton of the presynaptic neuron via its dopamine transporters as well as by diffusing through the neural membrane directly. By entering the presynaptic neuron, amphetamines force dopamine molecules out of their storage vesicles and expel them into the synaptic gap by making the dopamine transporters work in reverse.
Glycine and Taurine has been shown to alter dopamine levels in rat brains.
### Incentive salience
Dopamine's role in experiencing pleasure has been questioned by several researchers. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
### Dopamine, learning, and reward-seeking behavior
Dopaminergic neurons of the midbrain are the main source of dopamine in the brain. Dopamine has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral dopamine depletion is the hallmark of Parkinson's disease. Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder, as well as drug abuse.
Dopamine is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction. Recent researches suggest that the firing of dopaminergic neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain dopaminergic neurons increases, which consequently increases desire or motivation towards the reward. However, recent research finds that while some dopaminergic neurons react in the way expected of reward neurons, others do not and seem to respond in regard to unpredictability. This research finds the reward neurons predominate in the ventromedial region in the substantia nigra pars compacta as well as the ventral tegmental area. Neurons in these areas project mainly to the ventral striatum and thus might transmit value-related information in regard to reward values. The nonreward neurons are predominate in the dorsolateral area of the substantia nigra pars compacta which projects to the dorsal striatum and may relate to orienting behaviour. It has been suggested that the difference between these two types of dopaminergic neurons arises from their input: reward-linked ones have input from the basal forebrain while the nonreward-related ones from the lateral habenula.
### Animal studies
Clues to dopamine's role in motivation, desire, and pleasure have come from studies performed on animals. In one such study, rats were depleted of dopamine by up to 99 percent in the nucleus accumbens and neostriatum using 6-hydroxydopamine.
With this large reduction in dopamine, the rats would no longer eat by their own volition. The researchers then force-fed the rats food and noted whether they had the proper facial expressions indicating whether they liked or disliked it. The researchers of this study concluded that the reduction in dopamine did not reduce the rat's consummatory pleasure, only the desire to actually eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher "wanting" but not "liking" of sweet rewards.
### The effects of drugs that reduce dopamine activity
In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychotics) have been shown to reduce motivation, cause anhedonia (inability to experience pleasure), and long-term use has been associated with the irreversible movement disorder, tardive dyskinesia. Furthermore, antipsychotic drugs are associated with weight gain, diabetes, lactation, gynecomastia, drooling, dysphoria, fatigue, sexual dysfunction, and heart rhythm problems.
Selective D2/D3 agonists pramipexole and ropinirole, used to treat restless legs syndrome (RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).
### Opioid and cannabinoid transmission
Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).
This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.
Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptides or other neurotransmitters.
### Sociability
Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with social anxiety. Traits common to negative schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder, manic subjects can become hypersocial, as well as hypersexual. This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics.
### Processing of pain
Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central nervous system including the spinal cord, periaqueductal gray (PAG), thalamus, basal ganglia, insular cortex, and cingulate cortex. Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease. Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome, fibromyalgia, and restless legs syndrome. In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition. In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.
### Salience
Dopamine may also have a role in the salience of potentially important stimuli, such as sources of reward or of danger. This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.
### Behavior disorders
Deficient dopamine neurotransmission is implicated in attention-deficit hyperactivity disorder, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms. Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.
The long term use of levodopa in Parkinson's disease has been linked to dopamine dysregulation syndrome.
## Latent inhibition and creative drive
Dopamine in the mesolimbic pathway increases general arousal and goal directed behaviors and decreases latent inhibition; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity involving the frontal lobes, the temporal lobes, and mesolimbic dopamine.
## Chemoreceptor trigger zone
Dopamine is one of the neurotransmitters implicated in the control of nausea and vomiting via interactions in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist that functions as a prokinetic/antiemetic.
## Dopaminergic mind hypothesis
The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their hominid relatives by focusing on changes in dopamine. It theorizes that increased levels of dopamine were part of a general physiological adaptation due to an increased consumption of meat around two million years ago in Homo habilis, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the "high-dopamine" personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a "dopaminergic society" is an extremely goal-oriented, fast-paced, and even manic society, "given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments." In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are "typified by more conquest, competition, and aggression than nurturance and communality." Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans) support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes. However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.
# Links to psychosis
Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia. Increased dopaminergic functional activity, specifically in the mesolimbic pathway, is found in schizophrenic individuals. Anti-psychotic medications act largely as dopamine antagonists, inhibiting dopamine at the receptor level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors, while the atypical drugs also act on D1, D3 and D4 receptors. The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold, can temporarily cause psychosis, provides further evidence for this link.
# Therapeutic use
Levodopa is a dopamine precursor used in various forms to treat Parkinson's disease and dopa-responsive dystonia. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa or benserazide. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used. These include entacapone and tolcapone.
# Nonneural functions
## Immunoregulatory
Dopamine acts upon receptors present on immune cells, with all subtypes of dopamine receptors found on leukocytes. There is low expression of receptors on T lymphocytes and monocytes, moderate expression on neutrophils and eosinophils, and high expression on B cells and natural killer cells. The sympathetic innervation of lymphoid tissues is dopaminergic, and increases during stress. Dopamine can also affect immune cells in the spleen, bone marrow, and blood circulation. In addition, dopamine can be synthesized and released by the immune cells themselves.
The effects of dopamine on immune cells depend upon their physiological state. While dopamine activates resting T cells, it inhibits them when they are activated. Disorders such as schizophrenia and Parkinson's disease, in which there are changes in brain dopamine receptors and dopamine signaling pathways, are also associated with altered immune functioning.
## Peripheral effects
Dopamine also has effects when administered through an IV line outside the central nervous system. The brand name of this preparation is known as Intropin. The effects in this form are dose dependent.
- Dosages from 2 to 5 μg/kg/min are considered the "renal dose." At this low dosage, dopamine binds D1 receptors, dilating blood vessels, increasing blood flow to renal, mesenteric, and coronary arteries; and increasing overall renal perfusion. Dopamine therefore has a diuretic effect, potentially increasing urine output from 5 ml/kg/hr to 10 ml/kg/hr.
- Intermediate dosages from 5 to 10 μg/kg/min additionally have a positive inotropic and chronotropic effect through increased β1 receptor activation. It is used in patients with shock or heart failure to increase cardiac output and blood pressure. Dopamine begins to affect the heart at the lower doses, from about 3 μg/kg/min IV.
- High doses from 10 to 20 μg/kg/min is the "pressor" dose. This dose causes vasoconstriction, increases systemic vascular resistance, and increases blood pressure through α1 receptor activation; but can cause the vessels in the kidneys to constrict to the point where they will become non-functional.
## Renal effects
Dopamine induces natriuresis (sodium loss) in the kidneys.
# Dopamine and fruit browning
Polyphenol oxidases (PPOs) are a family of enzymes responsible for the browning of fresh fruits and vegetables when they are cut or bruised. These enzymes use molecular oxygen (O2) to oxidise various 1,2-diphenols to their corresponding quinones. The natural substrate for PPOs in bananas is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to other quinones. The quinones then polymerise and condense with amino acids and proteins to form brown pigments known as melanins. The quinones and melanins derived from dopamine may help protect damaged fruit and vegetables against growth of bacteria and fungi. | Dopamine
Template:Seealso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]
# Overview
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area.[1] Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.
Dopamine is available as an intravenous medication acting on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, because dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and dopa-responsive dystonia, L-DOPA, which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.
# History
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England.[2] It was named dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine (L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden.[3] Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but a neurotransmitter as well.
# Biochemistry
## Name and family
Dopamine has the chemical formula C6H3(OH)2-CH2-CH2-NH2. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol" and its abbreviation is "DA."
As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline) in the biosynthetic pathways for these neurotransmitters.
## Biosynthesis
Dopamine is biosynthesized in the body (mainly by nervous tissue and the medulla of the adrenal glands) first by the hydroxylation of the amino acid L-tyrosine to L-DOPA via the enzyme tyrosine 3-monooxygenase, also known as tyrosine hydroxylase, and then by the decarboxylation of L-DOPA by aromatic L-amino acid decarboxylase (which is often referred to as dopa decarboxylase). In some neurons, dopamine is further processed into norepinephrine by dopamine beta-hydroxylase.
In neurons, dopamine is packaged after synthesis into vesicles, which are then released into the synapse in response to a presynaptic action potential.
## Inactivation and degradation
Two major degradation pathways for dopamine exist. In most areas of the brain, including the striatum and basal ganglia, dopamine is inactivated by reuptake via the dopamine transporter (DAT1), then enzymatic breakdown by monoamine oxidase (MAOA and MAOB) into 3,4-dihydroxyphenylacetic acid. In the prefrontal cortex, however, there are very few dopamine transporter proteins, and dopamine is instead inactivated by reuptake via the norepinephrine transporter (NET), presumably on neighboring norepinephrine neurons, then enzymatic breakdown by catechol-O-methyl transferase (COMT) into 3-methoxytyramine.[4] The DAT1 pathway is roughly an order of magnitude faster than the NET pathway: in mice, dopamine concentrations decay with a half-life of 200 ms in the caudate nucleus (which uses the DAT1 pathway) versus 2,000 ms in the prefrontal cortex.[5] Dopamine that is not broken down by enzymes is repackaged into vesicles for reuse by VMAT2.
# Functions in the brain
Dopamine has many functions in the brain, including important roles in behavior and cognition, voluntary movement, motivation, punishment and reward, inhibition of prolactin production (involved in lactation and sexual gratification), sleep, mood, attention, working memory, and learning. Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are present chiefly in the ventral tegmental area (VTA) of the midbrain, the substantia nigra pars compacta, and the arcuate nucleus of the hypothalamus.
It has been hypothesized that dopamine transmits reward prediction error, although this has been questioned.[6] According to this hypothesis, the phasic responses of dopamine neurons are observed when an unexpected reward is presented. These responses transfer to the onset of a conditioned stimulus after repeated pairings with the reward. Further, dopamine neurons are depressed when the expected reward is omitted. Thus, dopamine neurons seem to encode the prediction error of rewarding outcomes. In nature, we learn to repeat behaviors that lead to maximizing rewards. Dopamine is therefore believed to provide a teaching signal to parts of the brain responsible for acquiring new behavior. Temporal difference learning provides a computational model describing how the prediction error of dopamine neurons is used as a teaching signal.
The reward system in insects uses octopamine, which is the presumed arthropod homolog of norepinephrine,[7] rather than dopamine. In insects, dopamine acts instead as a punishment signal and is necessary to form aversive memories.[8][9]
## Anatomy
Dopaminergic neurons form a neurotransmitter system which originates in substantia nigra pars compacta, ventral tegmental area (VTA), and hypothalamus. These project axons to large areas of the brain which are typically divided into four major pathways:
- Mesocortical pathway connects the ventral tegmental area to the frontal lobe of the pre-frontal cortex. Neurons with somas in the ventral tegmental area project axons into the pre-frontal cortex.
- Mesolimbic pathway carries dopamine from the ventral tegmental area to the nucleus accumbens via the amygdala and hippocampus. The somas of the projecting neurons are in the ventral tegmental area.
- Nigrostriatal pathway runs from the substantia nigra to the neostriatum. Somas in the substantia nigra project axons into the caudate nucleus and putamen. The pathway is involved in the basal ganglia motor loop.
- Tuberoinfundibular pathway runs from the hypothalamus to the pituitary gland.
This innervation explains many of the effects of activating this dopamine system. For instance, the mesolimbic pathway connects the VTA and nucleus accumbens; both are central to the brain reward system.[10]
Whilst the distinction between pathways is widely used, and is regarded as a “convenient heuristic when considering the dopamine system”, it is not absolute, and there is some overlap in the projection targets of each group of neurons.[11]
## Tonic and phasic activity
The level of extracellular dopamine is modulated by two mechanisms, tonic and phasic dopamine transmission. Tonic dopamine transmission occurs when small amounts of dopamine are released independently of neuronal activity, and is regulated by the activity of other neurons and neurotransmitter reuptake.[12] Phasic dopamine release results from the activity of the dopamine-containing cells themselves. This activity is characterized by irregular pacemaking activity of single spikes, and rapid bursts of typically 2-6 spikes in quick succession.[13][14] Concentrated bursts of activity result in a greater increase of extracellular dopamine levels than would be expected from the same number of spikes distributed over a longer period of time.[15]
## Movement
Via the dopamine receptors, D1-5, dopamine reduces the influence of the indirect pathway, and increases the actions of the direct pathway within the basal ganglia. Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson's disease, in which a person loses the ability to execute smooth, controlled movements.
## Cognition and frontal cortex
In the frontal lobes, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive functions, especially memory, attention, and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder. It has been found that D1 receptors[16] as well as D4 receptors[17] are responsible for the cognitive-enhancing effects of dopamine.
## Regulating prolactin secretion
Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactin from the anterior pituitary gland.[18] Dopamine produced by neurons in the arcuate nucleus of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the median eminence, which supply the pituitary gland. The lactotrope cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone (PIH), or prolactostatin.
## Motivation and pleasure
### Reinforcement
Dopamine is commonly associated with the reward system of the brain, providing feelings of enjoyment and reinforcement to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens and prefrontal cortex) by rewarding experiences such as food, sex, drugs, and neutral stimuli that become associated with them. Recent studies indicate that aggression may also stimulate the release of dopamine in this way.[19]
This theory is often discussed in terms of drugs such as cocaine, nicotine, and amphetamines, which directly or indirectly lead to an increase of dopamine in the mesolimbic reward pathway of the brain, and in relation to neurobiological theories of chemical addiction (not to be confused with psychological dependence), arguing that this dopamine pathway is pathologically altered in addicted persons.[20][21][22]
### Reuptake inhibition, expulsion
Cocaine and amphetamines inhibit the re-uptake of dopamine; however, they influence separate mechanisms of action. Cocaine is a dopamine transporter and norepinephrine transporter blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters. Like cocaine, amphetamines increase the concentration of dopamine in the synaptic gap, but by a different mechanism. Amphetamines and methamphetamine are similar in structure to dopamine, and so can enter the terminal bouton of the presynaptic neuron via its dopamine transporters as well as by diffusing through the neural membrane directly.[citation needed] By entering the presynaptic neuron, amphetamines force dopamine molecules out of their storage vesicles and expel them into the synaptic gap by making the dopamine transporters work in reverse.
Glycine and Taurine has been shown to alter dopamine levels in rat brains.
[23]
[24]
[25]
### Incentive salience
Dopamine's role in experiencing pleasure has been questioned by several researchers. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
### Dopamine, learning, and reward-seeking behavior
Dopaminergic neurons of the midbrain are the main source of dopamine in the brain.[26] Dopamine has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral dopamine depletion is the hallmark of Parkinson's disease.[26] Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder, as well as drug abuse.
Dopamine is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction.[26] Recent researches suggest that the firing of dopaminergic neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain dopaminergic neurons increases, which consequently increases desire or motivation towards the reward.[26] However, recent research finds that while some dopaminergic neurons react in the way expected of reward neurons, others do not and seem to respond in regard to unpredictability.[27] This research finds the reward neurons predominate in the ventromedial region in the substantia nigra pars compacta as well as the ventral tegmental area. Neurons in these areas project mainly to the ventral striatum and thus might transmit value-related information in regard to reward values.[27] The nonreward neurons are predominate in the dorsolateral area of the substantia nigra pars compacta which projects to the dorsal striatum and may relate to orienting behaviour.[27] It has been suggested that the difference between these two types of dopaminergic neurons arises from their input: reward-linked ones have input from the basal forebrain while the nonreward-related ones from the lateral habenula.[27]
### Animal studies
Clues to dopamine's role in motivation, desire, and pleasure have come from studies performed on animals. In one such study, rats were depleted of dopamine by up to 99 percent in the nucleus accumbens and neostriatum using 6-hydroxydopamine.[26]
With this large reduction in dopamine, the rats would no longer eat by their own volition. The researchers then force-fed the rats food and noted whether they had the proper facial expressions indicating whether they liked or disliked it. The researchers of this study concluded that the reduction in dopamine did not reduce the rat's consummatory pleasure, only the desire to actually eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher "wanting" but not "liking" of sweet rewards.[28]
### The effects of drugs that reduce dopamine activity
In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychotics) have been shown to reduce motivation, cause anhedonia (inability to experience pleasure), and long-term use has been associated with the irreversible movement disorder, tardive dyskinesia.[29] Furthermore, antipsychotic drugs are associated with weight gain, diabetes, lactation, gynecomastia, drooling, dysphoria, fatigue, sexual dysfunction, and heart rhythm problems.
Selective D2/D3 agonists pramipexole and ropinirole, used to treat restless legs syndrome (RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).[30]
### Opioid and cannabinoid transmission
Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).[31]
This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.[32]
Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptides or other neurotransmitters.
### Sociability
Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with social anxiety. Traits common to negative schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder, manic subjects can become hypersocial, as well as hypersexual.[citation needed] This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics.[33]
### Processing of pain
Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central nervous system including the spinal cord,[34] periaqueductal gray (PAG),[35] thalamus,[36] basal ganglia,[37][38] insular cortex,[39][40] and cingulate cortex.[41] Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease.[42] Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome,[43] fibromyalgia,[44][45] and restless legs syndrome.[46] In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition.[47] In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.
### Salience
Dopamine may also have a role in the salience of potentially important stimuli, such as sources of reward or of danger.[48] This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.
### Behavior disorders
Deficient dopamine neurotransmission is implicated in attention-deficit hyperactivity disorder, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms.[49] Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.[50]
The long term use of levodopa in Parkinson's disease has been linked to dopamine dysregulation syndrome.[51]
## Latent inhibition and creative drive
Dopamine in the mesolimbic pathway increases general arousal and goal directed behaviors and decreases latent inhibition; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity involving the frontal lobes, the temporal lobes, and mesolimbic dopamine.[52]
## Chemoreceptor trigger zone
Dopamine is one of the neurotransmitters implicated in the control of nausea and vomiting via interactions in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist that functions as a prokinetic/antiemetic.
## Dopaminergic mind hypothesis
The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their hominid relatives by focusing on changes in dopamine.[53] It theorizes that increased levels of dopamine were part of a general physiological adaptation due to an increased consumption of meat around two million years ago in Homo habilis, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the "high-dopamine" personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a "dopaminergic society" is an extremely goal-oriented, fast-paced, and even manic society, "given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments."[53] In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are "typified by more conquest, competition, and aggression than nurturance and communality."[53] Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans)[54] support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes.[55] However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.[56]
# Links to psychosis
Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia.[57] Increased dopaminergic functional activity, specifically in the mesolimbic pathway, is found in schizophrenic individuals. Anti-psychotic medications act largely as dopamine antagonists, inhibiting dopamine at the receptor level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors,[58] while the atypical drugs also act on D1, D3 and D4 receptors.[59][60] The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold,[61] can temporarily cause psychosis, provides further evidence for this link.[62]
# Therapeutic use
Levodopa is a dopamine precursor used in various forms to treat Parkinson's disease and dopa-responsive dystonia. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa or benserazide. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used. These include entacapone and tolcapone.
# Nonneural functions
## Immunoregulatory
Dopamine acts upon receptors present on immune cells, with all subtypes of dopamine receptors found on leukocytes. There is low expression of receptors on T lymphocytes and monocytes, moderate expression on neutrophils and eosinophils, and high expression on B cells and natural killer cells.[63] The sympathetic innervation of lymphoid tissues is dopaminergic, and increases during stress.[64] Dopamine can also affect immune cells in the spleen, bone marrow, and blood circulation.[65] In addition, dopamine can be synthesized and released by the immune cells themselves.[66][67]
The effects of dopamine on immune cells depend upon their physiological state. While dopamine activates resting T cells, it inhibits them when they are activated. Disorders such as schizophrenia and Parkinson's disease, in which there are changes in brain dopamine receptors and dopamine signaling pathways, are also associated with altered immune functioning.[68]
## Peripheral effects
Dopamine also has effects when administered through an IV line outside the central nervous system. The brand name of this preparation is known as Intropin. The effects in this form are dose dependent.
- Dosages from 2 to 5 μg/kg/min are considered the "renal dose."[69] At this low dosage, dopamine binds D1 receptors, dilating blood vessels, increasing blood flow to renal, mesenteric, and coronary arteries; and increasing overall renal perfusion.[70] Dopamine therefore has a diuretic effect, potentially increasing urine output from 5 ml/kg/hr to 10 ml/kg/hr.[citation needed]
- Intermediate dosages from 5 to 10 μg/kg/min additionally have a positive inotropic and chronotropic effect through increased β1 receptor activation. It is used in patients with shock or heart failure to increase cardiac output and blood pressure.[70] Dopamine begins to affect the heart at the lower doses, from about 3 μg/kg/min IV.[71]
- High doses from 10 to 20 μg/kg/min is the "pressor" dose.[citation needed] This dose causes vasoconstriction, increases systemic vascular resistance, and increases blood pressure through α1 receptor activation;[70] but can cause the vessels in the kidneys to constrict to the point where they will become non-functional.[citation needed]
## Renal effects
Dopamine induces natriuresis (sodium loss) in the kidneys.[72][73]
# Dopamine and fruit browning
Polyphenol oxidases (PPOs) are a family of enzymes responsible for the browning of fresh fruits and vegetables when they are cut or bruised. These enzymes use molecular oxygen (O2) to oxidise various 1,2-diphenols to their corresponding quinones. The natural substrate for PPOs in bananas is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to other quinones. The quinones then polymerise and condense with amino acids and proteins to form brown pigments known as melanins. The quinones and melanins derived from dopamine may help protect damaged fruit and vegetables against growth of bacteria and fungi.[74] | https://www.wikidoc.org/index.php/Dopamine | |
51bb6c848e0bf9db7743c00fbc026b57c2bbe500 | wikidoc | Dopp kit | Dopp kit
A Dopp kit also commonly referred to as a "DOB kit" is a small bag, made of leather, vinyl, or cloth that is used for storing men's grooming tools for travel. Common items kept in a Dopp kit are deodorant, a razor, shaving cream, comb, nail clippers, scissors, toothbrush, toothpaste, and cologne. The name derives from early 20th century leather craftsman Charles Doppelt.
The original Dopp kit was designed by Jerome Harris for his uncle Charles Doppelt, a German immigrant to Chicago in the early 1900s. The kits (and hence the term) became widely known during the Second World War when they were issued to GIs. Doppelt's company was purchased by Samsonite in the early 1970s.
Dopp kits were once a common gift given to adolescent males as they ascended from boyhood to adulthood.
Although the term was originally a trademark and may still be, it appears to have at least mostly become generic. | Dopp kit
A Dopp kit also commonly referred to as a "DOB kit" is a small bag, made of leather, vinyl, or cloth that is used for storing men's grooming tools for travel. Common items kept in a Dopp kit are deodorant, a razor, shaving cream, comb, nail clippers, scissors, toothbrush, toothpaste, and cologne. The name derives from early 20th century leather craftsman Charles Doppelt.
The original Dopp kit was designed by Jerome Harris for his uncle Charles Doppelt, a German immigrant to Chicago in the early 1900s. The kits (and hence the term) became widely known during the Second World War when they were issued to GIs. Doppelt's company was purchased by Samsonite in the early 1970s.
Dopp kits were once a common gift given to adolescent males as they ascended from boyhood to adulthood. [1]
Although the term was originally a trademark and may still be, it appears to have at least mostly become generic.
# External links
- Etymology from The Word Detective
- http://www.worldwidewords.org/qa/qa-dop1.htm
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Dopp_kit | |
b07aa3855507b796c73b52608a690329d1e3a885 | wikidoc | Doxapram | Doxapram
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Doxapram is a respiratory stimulant that is FDA approved for the treatment of Postanesthesia, Drug-Induced Central Nervous System Depression and Chronic Pulmonary Disease Associated with Acute Hypercapnia. Common adverse reactions include flushing, pruritus, diarrhea, nausea, vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
## Post-Anesthetic Use
- The recommended dose for I.V. administration is 0.5 – 1 mg/kg for a single injection and at 5-minute intervals. Careful observation of the patient during administration and for some time subsequently are advisable. The maximum total dosage by I.V. injection is 2 mg/kg.
- The solution is prepared by adding 250 mg of doxapram (12.5 mL) to 250 mL of dextrose 5% or 10% in water or normal saline solution. The infusion is initiated at a rate of approximately 5 mg/minute until a satisfactory respiratory response is observed, and maintained at a rate of 1 to 3 mg/minute. The rate of infusion should be adjusted to sustain the desired level of respiratory stimulation with a minimum of side effects. The maximum total dosage by infusion is 4 mg/kg, or approximately 300 mg for the average adult.
## Management of Drug-Induced CNS Depression
- Using Single and/or Repeat Single I.V. Injections
- Give priming dose of 2 mg/kg body weight and repeat in 5 minutes. The priming dose for moderate depression is 2 mg/kg and the priming dose for mild depression is 1 mg/kg.
- Repeat same dose q 1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since Doxapram does not affect the metabolism of CNS-depressant drugs.
- If relapse occurs, resume injections q 1 to 2h until arousal is sustained, or total maximum daily dose (3 grams) is given. After maximum dose has been given (3 grams), allow patient to sleep until 24 hours have elapsed from first injection of Doxapram, using assisted or automatic respiration if necessary.
- Repeat procedure the following day until patient breathes spontaneously and sustains desired level of consciousness, or until maximum dosage (3 grams) is given.
- Repetitive doses should be administered only to patients who have shown response to the initial dose.
- Failure to respond appropriately indicates the need for neurologic evaluation for a possible central nervous system source of sustained coma.
- By Intermittent I.V. Infusion.
- Give priming dose as in Method One.
- If patient wakens, watch for relapse; if no response, continue general supportive treatment for 1 to 2 hours and repeat priming dose of Doxapram.
- If some respiratory stimulation occurs, prepare I.V. infusion by adding 250 mg of Doxapram (12.5 mL) to 250 mL of saline or dextrose solution. Deliver at rate of 1 to 3 mg/min (60 to 180 mL/hr) according to size of patient and depth of coma. *Discontinue Doxapram if patient begins to waken or at end of 2 hours.
- Continue supportive treatment for ½ to 2 hours and repeat Step b. Do not exceed 3 grams/day.
## Chronic Obstructive Pulmonary Disease Associated with Acute Hypercapnia
- One vial of doxapram (400 mg) should be mixed with 180 mL of dextrose 5% or 10% or normal saline solution (concentration of 2 mg/mL). The infusion should be started at 1 to 2 mg/minute (½ to 1 mL/minute); if indicated, increase to a maximum of 3 mg/minute. *Arterial blood gases should be determined prior to the onset of doxapram’s administration and at least every half hour during the two hours of infusion to insure against the insidious development of CO2-RETENTION AND ACIDOSIS. Alteration of oxygen concentration or flow rate may necessitate adjustment in the rate of doxapram infusion.
- Predictable blood gas patterns are more readily established with a continuous infusion of doxapram. If the blood gases show evidence of deterioration, the infusion of doxapram should be discontinued.
- ADDITIONAL INFUSIONS BEYOND THE SINGLE MAXIMUM TWO HOUR ADMINISTRATION PERIOD ARE NOT RECOMMENDED.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Doxapram in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Doxapram in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Doxapram FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Doxapram in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Doxapram in pediatric patients.
# Contraindications
- Doxapram is contraindicated in patients with known hypersensitivity to the drug or any of the injection components.
- Doxapram should not be used in patients with epilepsy or other convulsive disorders.
- Doxapram is contraindicated in patients with proven or suspected pulmonary embolism.
- Doxapram is contraindicated in patients with mechanical disorders of ventilation such as mechanical obstruction, muscle paresis (including neuromuscular blockade), flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis, or other conditions resulting in restriction of the chest wall, muscles of respiration, or alveolar expansion.
- Doxapram is contraindicated in patients with evidence of head injury, cerebral vascular accident, or cerebral edema, and in those with significant cardiovascular impairment, uncompensated heart failure, severe coronary artery disease, or severe hypertension, including that associated with hyperthyroidism or pheochromocytoma.
# Warnings
- Doxapram should not be used in conjunction with mechanical ventilation. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol.
- Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources.
- Doxapram is neither an antagonist to muscle relaxant drugs nor a specific narcotic antagonist. More specific tests (eg, peripheral nerve stimulation, airway pressures, head lift, pulse oximetry, and end-tidal carbon dioxide) to assess adequacy of ventilation are recommended before administering doxapram.
- Doxapram should be administered with great care and only under careful supervision to patients with hypermetabolic states such as hyperthyroidism or pheochromocytoma.
- Since narcosis may recur after stimulation with doxapram, care should be taken to maintain close observation until the patient has been fully alert for ½ to 1 hour.
- In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of doxapram should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation.
- Doxapram alone may not stimulate adequate spontaneous breathing or provide sufficient arousal in patients who are severely depressed either due to respiratory failure or to CNS depressant drugs, but may be used as an adjunct to established supportive measures and resuscitative techniques.
- Because of the associated increased work of breathing, do not increase the rate of infusion of doxapram in severely ill patients in an attempt to lower pCO2.
# Adverse Reactions
## Clinical Trials Experience
Adverse reactions reported coincident with the administration of Doxapram (doxapram hydrochloride, USP) include:
### Central and Autonomic Nervous Systems
- Pyrexia, flushing, sweating; pruritus and paresthesia, such as a feeling of warmth, burning, or hot sensation, especially in the area of genitalia and perineum; apprehension, disorientation, pupillary dilatation, hallucinations, headache, dizziness, hyperactivity, involuntary movements, muscle spasticity, muscle fasciculations, increased deep tendon reflexes, clonus, bilateral Babinski, and convulsions.
### Respiratory
- Dyspnea, cough, hyperventilation, tachypnea, laryngospasm, bronchospasm, hiccough, and rebound hypoventilation.
### Cardiovascular
- Phlebitis, variations in heart rate, lowered T-waves, arrhythmias (including ventricular tachycardia and ventricular fibrillation), chest pain, tightness in chest. A mild to moderate increase in blood pressure is commonly noted and may be of concern in patients with severe cardiovascular diseases.
### Gastrointestinal
- Nausea, vomiting, diarrhea, desire to defecate.
### Genitourinary
- Stimulation of urinary bladder with spontaneous voiding; urinary retention. Elevation of BUN and albuminuria.
### Hemic and Lymphatic
- Hemolysis with rapid infusion. A decrease in hemoglobin, hematocrit, or red blood cell count has been observed in postoperative patients. In the presence of pre-existing leukopenia, a further decrease in WBC has been observed following anesthesia and treatment with doxapram hydrochloride.
## Postmarketing Experience
There is limited information regarding Doxapram Postmarketing Experience in the drug label.
# Drug Interactions
- Administration of doxapram to patients who are receiving sympathomimetic or monoamine oxidase inhibiting drugs may result in an additive pressor effect.
- In patients who have received neuromuscular blocking agents, doxapram may temporarily mask the residual effects of these drugs.
- In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of doxapram should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation.
- There may be an interaction between doxapram and aminophylline and between doxapram and theophylline manifested by increased skeletal muscle activity, agitation, and hyperactivity.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats at doses up to 1.6 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to doxapram. There are, however, no adequate and well-controlled studies in pregnant women. Because the animals in the reproduction studies were dosed by the IM and oral routes and animal reproduction studies, in general, are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Doxapram in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Doxapram during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when doxapram hydrochloride is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness in pediatric patients below the age of 12 years have not been established. This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
- Premature neonates given doxapram have developed hypertension, irritability, jitteriness, hyperglycemia, glucosuria, abdominal distension, increased gastric residuals, vomiting, bloody stools, necrotizing enterocolitis, erratic limb movements, excessive crying, disturbed sleep, premature eruption of teeth, and QT prolongation that has resulted in heart block. In premature neonates with risk factors such as a previous seizure, perinatal asphyxia, or intracerebral hemorrhage, seizures have occurred. In many instances, doxapram was administered following administration of xanthine derivatives such as caffeine, aminophylline or theophylline.
### Geriatic Use
There is no FDA guidance on the use of Doxapram in geriatric settings.
### Gender
There is no FDA guidance on the use of Doxapram with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Doxapram with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Doxapram in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Doxapram in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Doxapram in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Doxapram in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Doxapram Administration in the drug label.
### Monitoring
There is limited information regarding Doxapram Monitoring in the drug label.
# IV Compatibility
### Diluent Compatibility
- Doxapram hydrochloride is compatible with 5% and 10% dextrose in water or normal saline.
### Incompatibility
- Admixture of doxapram with alkaline solutions such as 2.5% thiopental sodium, sodium bicarbonate, furosemide, or aminophylline will result in precipitation or gas formation.
- Doxapram is also not compatible with ascorbic acid, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefuroxime sodium, folic acid, dexamethasone disodium phosphate, diazepam, hydrocortisone sodium phosphate, methylprednisolone sodium, or hydrocortisone sodium succinate.
- Admixture of doxapram and ticarcillin disodium results in an 18% loss of doxapram in 3 hours. When doxapram is mixed with minocycline hydrochloride, there is a loss of 8% of doxapram in 3 hours and a 13% loss of doxapram in 6 hours.
# Overdosage
### Signs and Symptoms
- Symptoms of overdosage are extensions of the pharmacologic effects of the drug. Excessive pressor effect, such as hypertension, tachycardia, skeletal muscle hyperactivity, and enhanced deep tendon reflexes may be early signs of overdosage. Therefore, the blood pressure, pulse rate, and deep tendon reflexes should be evaluated periodically and the dosage or infusion rate adjusted accordingly.
- Other effects may include agitation, confusion, sweating, cough, and dyspnea.
- Convulsive seizures are unlikely at recommended dosages. In unanesthetized animals, the convulsant dose is 70 times greater than the respiratory stimulant dose. Intravenous LD50 values in the mouse and rat were approximately 75 mg/kg and in the cat and dog were 40 to 80 mg/kg.
- Except for management of chronic obstructive pulmonary disease associated with acute hypercapnia, the maximum recommended dosage is 3 GRAMS/24 HOURS.
### Management
- There is no specific antidote for doxapram. Management should be symptomatic. Anticonvulsants, along with oxygen and resuscitative equipment should be readily available to manage overdosage manifested by excessive central nervous system stimulation. Slow administration of the drug and careful observation of the patient during administration and for some time subsequently are advisable. These precautions are to assure that the protective reflexes have been restored and to prevent possible post-hyperventilation or hypoventilation.
- There is no evidence that doxapram is dialyzable; further, the half-life of doxapram makes it unlikely that dialysis would be appropriate in managing overdose with this drug.
# Pharmacology
## Mechanism of Action
There is limited information regarding Doxapram Mechanism of Action in the drug label.
## Structure
- Doxapram hydrochloride is a white to off-white, crystalline powder, sparingly soluble in water, alcohol and chloroform. Chemically, doxapram hydrochloride is 1-ethyl-4-2-(4-morpholinyl)ethyl-3,3-diphenyl-2-pyrrolidinone monohydrochloride, monohydrate.
- The chemical structure is:
C24H31ClN2O2 - H2O M.W. 432.98
## Pharmacodynamics
- Doxapram hydrochloride produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. As the dosage level is increased, the central respiratory centers in the medulla are stimulated with progressive stimulation of other parts of the brain and spinal cord. The onset of respiratory stimulation following the recommended single intravenous injection of doxapram hydrochloride usually occurs in 20 to 40 seconds with peak effect at 1 to 2 minutes. The duration of effect may vary from 5 to 12 minutes. The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate.
- A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic state than in normovolemic state. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted.
- Although opiate-induced respiratory depression is antagonized by doxapram, the analgesic effect is not affected.
## Pharmacokinetics
- Doxapram is metabolized via ring hydroxylation to ketodoxapram, an active metabolite readily detected in the plasma.
## Nonclinical Toxicology
- No carcinogenic or mutagenic studies have been performed using doxapram. Doxapram did not adversely affect the breeding performance of rats.
# Clinical Studies
There is limited information regarding Doxapram Clinical Studies in the drug label.
# How Supplied
- Doxapram Injection (doxapram hydrochloride injection, USP) is available in boxes of six 20 mL multiple dose vials containing 20 mg of doxapram hydrochloride per mL with benzyl alcohol 0.9% as the preservative (NDC 60977-144-02).
## Storage
- Store at Controlled Room Temperature, Between 20˚C to 25˚C (68˚F to 77˚F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Doxapram Patient Counseling Information in the drug label.
# Precautions with Alcohol
- Alcohol-Doxapram interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Dopram
# Look-Alike Drug Names
There is limited information regarding Doxapram Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Doxapram
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
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# Overview
Doxapram is a respiratory stimulant that is FDA approved for the treatment of Postanesthesia, Drug-Induced Central Nervous System Depression and Chronic Pulmonary Disease Associated with Acute Hypercapnia. Common adverse reactions include flushing, pruritus, diarrhea, nausea, vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
## Post-Anesthetic Use
- The recommended dose for I.V. administration is 0.5 – 1 mg/kg for a single injection and at 5-minute intervals. Careful observation of the patient during administration and for some time subsequently are advisable. The maximum total dosage by I.V. injection is 2 mg/kg.
- The solution is prepared by adding 250 mg of doxapram (12.5 mL) to 250 mL of dextrose 5% or 10% in water or normal saline solution. The infusion is initiated at a rate of approximately 5 mg/minute until a satisfactory respiratory response is observed, and maintained at a rate of 1 to 3 mg/minute. The rate of infusion should be adjusted to sustain the desired level of respiratory stimulation with a minimum of side effects. The maximum total dosage by infusion is 4 mg/kg, or approximately 300 mg for the average adult.
## Management of Drug-Induced CNS Depression
- Using Single and/or Repeat Single I.V. Injections
- Give priming dose of 2 mg/kg body weight and repeat in 5 minutes. The priming dose for moderate depression is 2 mg/kg and the priming dose for mild depression is 1 mg/kg.
- Repeat same dose q 1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since Doxapram does not affect the metabolism of CNS-depressant drugs.
- If relapse occurs, resume injections q 1 to 2h until arousal is sustained, or total maximum daily dose (3 grams) is given. After maximum dose has been given (3 grams), allow patient to sleep until 24 hours have elapsed from first injection of Doxapram, using assisted or automatic respiration if necessary.
- Repeat procedure the following day until patient breathes spontaneously and sustains desired level of consciousness, or until maximum dosage (3 grams) is given.
- Repetitive doses should be administered only to patients who have shown response to the initial dose.
- Failure to respond appropriately indicates the need for neurologic evaluation for a possible central nervous system source of sustained coma.
- By Intermittent I.V. Infusion.
- Give priming dose as in Method One.
- If patient wakens, watch for relapse; if no response, continue general supportive treatment for 1 to 2 hours and repeat priming dose of Doxapram.
- If some respiratory stimulation occurs, prepare I.V. infusion by adding 250 mg of Doxapram (12.5 mL) to 250 mL of saline or dextrose solution. Deliver at rate of 1 to 3 mg/min (60 to 180 mL/hr) according to size of patient and depth of coma. *Discontinue Doxapram if patient begins to waken or at end of 2 hours.
- Continue supportive treatment for ½ to 2 hours and repeat Step b. Do not exceed 3 grams/day.
## Chronic Obstructive Pulmonary Disease Associated with Acute Hypercapnia
- One vial of doxapram (400 mg) should be mixed with 180 mL of dextrose 5% or 10% or normal saline solution (concentration of 2 mg/mL). The infusion should be started at 1 to 2 mg/minute (½ to 1 mL/minute); if indicated, increase to a maximum of 3 mg/minute. *Arterial blood gases should be determined prior to the onset of doxapram’s administration and at least every half hour during the two hours of infusion to insure against the insidious development of CO2-RETENTION AND ACIDOSIS. Alteration of oxygen concentration or flow rate may necessitate adjustment in the rate of doxapram infusion.
- Predictable blood gas patterns are more readily established with a continuous infusion of doxapram. If the blood gases show evidence of deterioration, the infusion of doxapram should be discontinued.
- ADDITIONAL INFUSIONS BEYOND THE SINGLE MAXIMUM TWO HOUR ADMINISTRATION PERIOD ARE NOT RECOMMENDED.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Doxapram in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Doxapram in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Doxapram FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Doxapram in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Doxapram in pediatric patients.
# Contraindications
- Doxapram is contraindicated in patients with known hypersensitivity to the drug or any of the injection components.
- Doxapram should not be used in patients with epilepsy or other convulsive disorders.
- Doxapram is contraindicated in patients with proven or suspected pulmonary embolism.
- Doxapram is contraindicated in patients with mechanical disorders of ventilation such as mechanical obstruction, muscle paresis (including neuromuscular blockade), flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis, or other conditions resulting in restriction of the chest wall, muscles of respiration, or alveolar expansion.
- Doxapram is contraindicated in patients with evidence of head injury, cerebral vascular accident, or cerebral edema, and in those with significant cardiovascular impairment, uncompensated heart failure, severe coronary artery disease, or severe hypertension, including that associated with hyperthyroidism or pheochromocytoma.
# Warnings
- Doxapram should not be used in conjunction with mechanical ventilation. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol.
- Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources.
- Doxapram is neither an antagonist to muscle relaxant drugs nor a specific narcotic antagonist. More specific tests (eg, peripheral nerve stimulation, airway pressures, head lift, pulse oximetry, and end-tidal carbon dioxide) to assess adequacy of ventilation are recommended before administering doxapram.
- Doxapram should be administered with great care and only under careful supervision to patients with hypermetabolic states such as hyperthyroidism or pheochromocytoma.
- Since narcosis may recur after stimulation with doxapram, care should be taken to maintain close observation until the patient has been fully alert for ½ to 1 hour.
- In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of doxapram should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation.
- Doxapram alone may not stimulate adequate spontaneous breathing or provide sufficient arousal in patients who are severely depressed either due to respiratory failure or to CNS depressant drugs, but may be used as an adjunct to established supportive measures and resuscitative techniques.
- Because of the associated increased work of breathing, do not increase the rate of infusion of doxapram in severely ill patients in an attempt to lower pCO2.
# Adverse Reactions
## Clinical Trials Experience
Adverse reactions reported coincident with the administration of Doxapram (doxapram hydrochloride, USP) include:
### Central and Autonomic Nervous Systems
- Pyrexia, flushing, sweating; pruritus and paresthesia, such as a feeling of warmth, burning, or hot sensation, especially in the area of genitalia and perineum; apprehension, disorientation, pupillary dilatation, hallucinations, headache, dizziness, hyperactivity, involuntary movements, muscle spasticity, muscle fasciculations, increased deep tendon reflexes, clonus, bilateral Babinski, and convulsions.
### Respiratory
- Dyspnea, cough, hyperventilation, tachypnea, laryngospasm, bronchospasm, hiccough, and rebound hypoventilation.
### Cardiovascular
- Phlebitis, variations in heart rate, lowered T-waves, arrhythmias (including ventricular tachycardia and ventricular fibrillation), chest pain, tightness in chest. A mild to moderate increase in blood pressure is commonly noted and may be of concern in patients with severe cardiovascular diseases.
### Gastrointestinal
- Nausea, vomiting, diarrhea, desire to defecate.
### Genitourinary
- Stimulation of urinary bladder with spontaneous voiding; urinary retention. Elevation of BUN and albuminuria.
### Hemic and Lymphatic
- Hemolysis with rapid infusion. A decrease in hemoglobin, hematocrit, or red blood cell count has been observed in postoperative patients. In the presence of pre-existing leukopenia, a further decrease in WBC has been observed following anesthesia and treatment with doxapram hydrochloride.
## Postmarketing Experience
There is limited information regarding Doxapram Postmarketing Experience in the drug label.
# Drug Interactions
- Administration of doxapram to patients who are receiving sympathomimetic or monoamine oxidase inhibiting drugs may result in an additive pressor effect.
- In patients who have received neuromuscular blocking agents, doxapram may temporarily mask the residual effects of these drugs.
- In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of doxapram should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation.
- There may be an interaction between doxapram and aminophylline and between doxapram and theophylline manifested by increased skeletal muscle activity, agitation, and hyperactivity.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats at doses up to 1.6 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to doxapram. There are, however, no adequate and well-controlled studies in pregnant women. Because the animals in the reproduction studies were dosed by the IM and oral routes and animal reproduction studies, in general, are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Doxapram in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Doxapram during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when doxapram hydrochloride is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness in pediatric patients below the age of 12 years have not been established. This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
- Premature neonates given doxapram have developed hypertension, irritability, jitteriness, hyperglycemia, glucosuria, abdominal distension, increased gastric residuals, vomiting, bloody stools, necrotizing enterocolitis, erratic limb movements, excessive crying, disturbed sleep, premature eruption of teeth, and QT prolongation that has resulted in heart block. In premature neonates with risk factors such as a previous seizure, perinatal asphyxia, or intracerebral hemorrhage, seizures have occurred. In many instances, doxapram was administered following administration of xanthine derivatives such as caffeine, aminophylline or theophylline.
### Geriatic Use
There is no FDA guidance on the use of Doxapram in geriatric settings.
### Gender
There is no FDA guidance on the use of Doxapram with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Doxapram with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Doxapram in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Doxapram in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Doxapram in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Doxapram in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Doxapram Administration in the drug label.
### Monitoring
There is limited information regarding Doxapram Monitoring in the drug label.
# IV Compatibility
### Diluent Compatibility
- Doxapram hydrochloride is compatible with 5% and 10% dextrose in water or normal saline.
### Incompatibility
- Admixture of doxapram with alkaline solutions such as 2.5% thiopental sodium, sodium bicarbonate, furosemide, or aminophylline will result in precipitation or gas formation.
- Doxapram is also not compatible with ascorbic acid, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefuroxime sodium, folic acid, dexamethasone disodium phosphate, diazepam, hydrocortisone sodium phosphate, methylprednisolone sodium, or hydrocortisone sodium succinate.
- Admixture of doxapram and ticarcillin disodium results in an 18% loss of doxapram in 3 hours. When doxapram is mixed with minocycline hydrochloride, there is a loss of 8% of doxapram in 3 hours and a 13% loss of doxapram in 6 hours.
# Overdosage
### Signs and Symptoms
- Symptoms of overdosage are extensions of the pharmacologic effects of the drug. Excessive pressor effect, such as hypertension, tachycardia, skeletal muscle hyperactivity, and enhanced deep tendon reflexes may be early signs of overdosage. Therefore, the blood pressure, pulse rate, and deep tendon reflexes should be evaluated periodically and the dosage or infusion rate adjusted accordingly.
- Other effects may include agitation, confusion, sweating, cough, and dyspnea.
- Convulsive seizures are unlikely at recommended dosages. In unanesthetized animals, the convulsant dose is 70 times greater than the respiratory stimulant dose. Intravenous LD50 values in the mouse and rat were approximately 75 mg/kg and in the cat and dog were 40 to 80 mg/kg.
- Except for management of chronic obstructive pulmonary disease associated with acute hypercapnia, the maximum recommended dosage is 3 GRAMS/24 HOURS.
### Management
- There is no specific antidote for doxapram. Management should be symptomatic. Anticonvulsants, along with oxygen and resuscitative equipment should be readily available to manage overdosage manifested by excessive central nervous system stimulation. Slow administration of the drug and careful observation of the patient during administration and for some time subsequently are advisable. These precautions are to assure that the protective reflexes have been restored and to prevent possible post-hyperventilation or hypoventilation.
- There is no evidence that doxapram is dialyzable; further, the half-life of doxapram makes it unlikely that dialysis would be appropriate in managing overdose with this drug.
# Pharmacology
## Mechanism of Action
There is limited information regarding Doxapram Mechanism of Action in the drug label.
## Structure
- Doxapram hydrochloride is a white to off-white, crystalline powder, sparingly soluble in water, alcohol and chloroform. Chemically, doxapram hydrochloride is 1-ethyl-4-2-(4-morpholinyl)ethyl-3,3-diphenyl-2-pyrrolidinone monohydrochloride, monohydrate.
- The chemical structure is:
C24H31ClN2O2 • H2O M.W. 432.98
## Pharmacodynamics
- Doxapram hydrochloride produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. As the dosage level is increased, the central respiratory centers in the medulla are stimulated with progressive stimulation of other parts of the brain and spinal cord. The onset of respiratory stimulation following the recommended single intravenous injection of doxapram hydrochloride usually occurs in 20 to 40 seconds with peak effect at 1 to 2 minutes. The duration of effect may vary from 5 to 12 minutes. The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate.
- A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic state than in normovolemic state. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted.
- Although opiate-induced respiratory depression is antagonized by doxapram, the analgesic effect is not affected.
## Pharmacokinetics
- Doxapram is metabolized via ring hydroxylation to ketodoxapram, an active metabolite readily detected in the plasma.
## Nonclinical Toxicology
- No carcinogenic or mutagenic studies have been performed using doxapram. Doxapram did not adversely affect the breeding performance of rats.
# Clinical Studies
There is limited information regarding Doxapram Clinical Studies in the drug label.
# How Supplied
- Doxapram Injection (doxapram hydrochloride injection, USP) is available in boxes of six 20 mL multiple dose vials containing 20 mg of doxapram hydrochloride per mL with benzyl alcohol 0.9% as the preservative (NDC 60977-144-02).
## Storage
- Store at Controlled Room Temperature, Between 20˚C to 25˚C (68˚F to 77˚F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Doxapram Patient Counseling Information in the drug label.
# Precautions with Alcohol
- Alcohol-Doxapram interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Dopram
# Look-Alike Drug Names
There is limited information regarding Doxapram Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Dopram | |
ae75a7aa9e39633356184bb81d2f196df966f18c | wikidoc | Quazepam | Quazepam
# Disclaimer
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# Overview
Quazepam is a Benzodiazepine that is FDA approved for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Common adverse reactions include drowsiness, headache, fatigue, dizziness, dry mouth, dyspepsia.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- QUAZEPAM® (quazepam) is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of QUAZEPAM has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of QUAZEPAM has been established in chronic insomnia in a sleep lab (polysomnographic) study of 28 nights duration. Because insomnia is often transient and intermittent, the prolonged administration of QUAZEPAM Tablets is generally not necessary or recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered.
### Dosage
- Use the lowest dose effective for the patient, as important adverse effects of QUAZEPAM are dose related.
- The recommended initial dose is 7.5 mg. The 7.5 mg dose can be increased to 15 mg if necessary for efficacy.
- The 7.5 mg dose can be achieved by splitting the 15 mg tablet along the score line.
- Elderly and debilitated patients may be more sensitive to benzodiazepines.
### DOSAGE FORMS AND STRENGTHS
- Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (QUAZEPAM) on the other.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Quazepam in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Quazepam in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Quazepam in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Quazepam in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Quazepam in pediatric patients.
# Contraindications
- QUAZEPAM is contraindicated in patients with known hypersensitivity to quazepam or other benzodiazepines. Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of QUAZEPAM. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Patients who develop such reactions should not be rechallenged with QUAZEPAM.
- Contraindicated in patients with established or suspected sleep apnea, or with pulmonary insufficiency.
# Warnings
- QUAZEPAM is a central nervous system (CNS) depressant and can impair daytime function in some patients even when used as prescribed. Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam (i.e. less than formal psychomotor testing). While pharmacodynamic tolerance or adaptation to some adverse depressant effects of QUAZEPAM may develop, patients using QUAZEPAM should be cautioned against driving or engaging in other hazardous activities or activities requiring complete mental alertness.
- Additive effects occur with concomitant use of other CNS depressants (e.g., other benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use. Downward dose adjustment of QUAZEPAM and concomitant CNS depressants should be considered. The potential for adverse drug interactions continues for several days following discontinuation of QUAZEPAM, until serum levels of both active parent drug and psychoactive metabolites decline.
- Use of QUAZEPAM with other sedative-hypnotics is not recommended. Alcohol generally should not be used during treatment with QUAZEPAM. The risk of next-day psychomotor impairment is increased if QUAZEPAM is taken with less than a full night of sleep remaining (7- to 8 hours); if higher than the recommended dose is taken; if co-administered with other CNS depressants.
- A withdrawal syndrome similar to that from alcohol (e.g., convulsions, tremor, abdominal and muscle cramps, vomiting, and sweating) can occur following abrupt discontinuation of QUAZEPAM. The more severe withdrawal effects are usually limited to patients taking higher than recommended doses over an extended time. Abrupt discontinuation should be avoided in such patients, and the dose gradually tapered. Prescribers should monitor patients for tolerance, abuse, and dependence.
- Milder withdrawal symptoms (e.g., dysphoria and insomnia) can occur following abrupt discontinuation of benzodiazepines taken at therapeutic levels for short periods.
- Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative-hypnotic drugs.
- Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including QUAZEPAM. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis.
- Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with QUAZEPAM should not be rechallenged with the drug.
- Abnormal thinking and behavior changes have been reported in patients treated with sedative-hypnotics including QUAZEPAM. Some of these changes include decreased inhibition (e.g., aggressiveness and extroversion that seemed out of character), bizarre behavior, and depersonalization. Visual and auditory hallucinations have also been reported. Amnesia, and other neuro-psychiatric symptoms may occur.
- Paradoxical reactions such as stimulation, agitation, increased muscle spasticity, and sleep disturbances may occur unpredictably.
- Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake, with amnesia for the event) have been reported with use of sedative-hypnotics. These behaviors can occur with initial treatment or in patients previously tolerant of QUAZEPAM or other sedative-hypnotics. Although these behaviors can occur with use at therapeutic doses, risk is increased by higher doses or concomitant use of alcohol or other CNS depressants. Due to risk to the patient and community, QUAZEPAM should be discontinued if "sleep-driving" occurs.
- Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events.
- Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered.
# Adverse Reactions
## Clinical Trials Experience
- The following serious adverse reactions are discussed in greater detail in other sections of the label:
- CNS-depressant effects and next-day impairment
- Benzodiazepine withdrawal syndrome
- Abnormal thinking and behavior changes, and complex behaviors
- Worsening of depression
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- The table shows adverse reactions occurring at an incidence of 1% or greater in relatively short-duration, placebo-controlled clinical trials of QUAZEPAM. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in actual practice.
- A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.
## Postmarketing Experience
There is limited information regarding Quazepam Postmarketing Experience in the drug label.
# Drug Interactions
- Benzodiazepines, including QUAZEPAM, produce additive CNS depressant effects when co-administered with ethanol or other CNS depressants (e.g. psychotropic medications, anticonvulsants, antihistamines). Downward dose adjustment of QUAZEPAM and/or concomitant CNS depressants may be necessary because of additive effects.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- There are no adequate and well-controlled studies in pregnant women. Administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding. In addition, infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can development dependence, and subsequently withdrawal, during the postnatal period. Although administration of quazepam to pregnant animals did not indicate a risk for adverse effects on morphological development at clinically relevant doses, data for other benzodiazepines suggest the possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines. QUAZEPAM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Developmental toxicity studies of quazepam in mice at doses up to 400 times the human dose (15 mg) revealed no major drug-related malformations. Minor fetal skeletal variations that occurred were delayed ossification of the sternum, vertebrae, distal phalanges and supraoccipital bones, at doses approximately 70 and 400 times the human dose. A developmental toxicity study of quazepam in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Quazepam in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Quazepam during labor and delivery.
### Nursing Mothers
- Quazepam and its metabolites are excreted in human milk. Caution should be exercised when administering QUAZEPAM to a nursing woman.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- QUAZEPAM may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of QUAZEPAM and observed closely.
- Elderly and debilitated patients may be more sensitive to benzodiazepines, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- A double-blind controlled sleep laboratory study (N=30) compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.
### Gender
There is no FDA guidance on the use of Quazepam with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Quazepam with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Quazepam in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Quazepam in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Quazepam in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Quazepam in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
- Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam
- Prescribers should monitor patients for tolerance, abuse, and dependence.
- Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered.
# IV Compatibility
There is limited information regarding IV Compatibility of Quazepam in the drug label.
# Overdosage
- Contact a poison control center for up-to-date information on the management of benzodiazepine overdose.
- Manifestations of QUAZEPAM overdose include somnolence, confusion, and coma. General supportive measures should be employed, along with immediate gastric lavage. Dialysis is of limited value. Flumazenil may be useful, but can contribute to the appearance of neurological symptoms including convulsions. Hypotension may be treated by appropriate medical intervention. Animal experiments suggest that forced diuresis or hemodialysis are of little value in treating QUAZEPAM overdose. As with the management of intentional overdose with any drug, the possibility of multiple drug ingestion should be considered.
### DRUG ABUSE AND DEPENDENCE
- Quazepam is classified as a Schedule IV controlled substance by federal regulation.
- Addiction-prone individuals (e.g. history of drug addiction or alcoholism) should be under careful surveillance when receiving QUAZEPAM because of increased risk of abuse and dependence. Benzodiazepine withdrawal symptoms can occur following discontinuation of QUAZEPAM.
- Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.
- Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.
# Pharmacology
## Mechanism of Action
- Quazepam, like other central nervous system agents of the 1,4-benzodiazepine class, presumably exerts its effects by binding to stereo-specific receptors at several sites within the central nervous system (CNS). The exact mechanism of action is unknown.
## Structure
- QUAZEPAM contains quazepam, a trifluoroethyl benzodiazepine hypnotic agent, having the chemical name 7-chloro-5- (o-fluoro-phenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazepine-2-thione and the following structural formula:
- Quazepam has the empirical formula C17H11CIF4N2S, and a molecular weight of 386.8. It is a white crystalline compound, soluble in ethanol and insoluble in water. Each QUAZEPAM Tablet contains 15 mg of quazepam. The inactive ingredients for QUAZEPAM Tablets include cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Quazepam in the drug label.
## Pharmacokinetics
- Quazepam is rapidly (absorption half-life of about 30 minutes) and well absorbed from the gastrointestinal tract. The peak plasma concentration of quazepam is approximately 20 ng/mL after a 15 mg dose and occurs at about 2 hours.
- Quazepam, the active parent compound, is extensively metabolized in the liver; two of the plasma metabolites are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. All three compounds show CNS depressant activity.
- The degree of plasma protein binding for quazepam and its two major metabolites is greater than 95%.
- Following administration of 14C-quazepam, 31% of the dose appeared in the urine and 23% in the feces over five days; only trace amounts of unchanged drug were present in the urine.
- The mean elimination half-life of quazepam and 2-oxoquazepam is 39 hours and that of N-desalkyl-2-oxoquazepam is 73 hours. Steady-state levels of quazepam and 2-oxoquazepam are attained by the seventh daily dose and that of N-desalkyl-2-oxoquazepam by the thirteenth daily dose.
- Geriatrics: The pharmacokinetics of quazepam and 2-oxoquazepam in geriatric subjects are comparable to those seen in young adults; as with desalkyl metabolites of other benzodiazepines, the elimination half-life of N-desalkyl-2-oxoquazepam in geriatric patients is about twice that of young adults.
- Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.
## Nonclinical Toxicology
- Quazepam showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters.
- Quazepam was negative in the bacterial reverse mutation (Ames) assay and equivocal in the mouse lymphoma tk assay.
- Reproduction studies in mice conducted with quazepam at doses equal to 60 and 180 times the human dose of 15 mg produced slight reductions in fertility rate. Similar reductions in fertility rate have been reported in mice dosed with other benzodiazepines, and is believed to be related to the sedative effects of these drugs at high doses..
# Clinical Studies
- The effectiveness of QUAZEPAM was established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of QUAZEPAM was established in chronic insomnia in a sleep laboratory (polysomnographic) study of 28 nights duration.
- In the sleep laboratory study, QUAZEPAM significantly decreased sleep latency and total wake time, and significantly increased total sleep time and percent sleep time, for one or more nights. QUAZEPAM 15 mg was effective on the first night of administration. Sleep latency, total wake time and wake time after sleep onset were still decreased and percent sleep time was still increased for several nights after the drug was discontinued. Percent slow wave sleep was decreased, and REM sleep was essentially unchanged. No transient sleep disturbance, such as “rebound insomnia,” was observed after withdrawal of the drug in sleep laboratory studies in 12 patients using 15 mg doses.
- In outpatient studies, QUAZEPAM Tablets improved all subjective measures of sleep including sleep latency, duration of sleep, number of awakenings, occurrence of early morning awakening, and sleep quality. Some effects were evident on the first night of administration of QUAZEPAM (sleep latency, number of awakenings, and duration of sleep).
- A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be effective. Caution must be used in interpreting this data due to the small size of the study.
# How Supplied
- QUAZEPAM Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (QUAZEPAM) on the other.
## Storage
- Store QUAZEPAM® Tablets at controlled room temperature 20°-25°C (68°-77°F).
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
Package Label – Principal Display Panel – 15mg 100 Tablet Carton
100 tablets
QUAZEPAM (quazepam tablets, USP)
C-IV
15 mg Tablets
Provide a MEDICATION GUIDE each time this drug is dispensed to a patient. MEDICATION GUIDES are enclosed.
Rx only
### Ingredients and Appearance
# Patient Counseling Information
- See FDA-approved patient labeling (Medication Guide).
- Inform patients about the benefits and risks of QUAZEPAM, stressing the importance of use as directed. Assist patients in understanding the Medication Guide and instruct them to read it with each prescription refill.
- CNS depressant Effects and Next-Day Impairment
- Tell patients that QUAZEPAM can cause next-day impairment, even in the absence of symptoms. Caution patients against driving or engaging in other hazardous activities or activities requiring complete mental alertness when using QUAZEPAM. Tell patients that daytime impairment may persist for several days following discontinuation of QUAZEPAM.
- Withdrawal
- Instruct patients to contact you before stopping or decreasing the dose of QUAZEPAM, because withdrawal symptoms can occur.
- Abnormal thinking and behavior change
- Instruct patients that sedative hypnotics can cause abnormal thinking and behavior change, including “sleep-driving” and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop any of these symptoms.
- Severe Allergic Reactions
- Inform patients that severe allergic reactions can occur from QUAZEPAM. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if these occur.
- Suicide
- Tell patients that QUAZEPAM can worsen depression, and to immediately report any suicidal thoughts.
- Alcohol and other drugs
- Ask patients about alcohol consumption, medicines they are taking now, and drugs they may be taking without a prescription. Advise patients that alcohol generally should not be used during treatment with QUAZEPAM.
- Pregnancy
- Instruct patients to inform you if they are nursing or pregnant, or may become pregnant while taking QUAZEPAM.
- Tolerance, Abuse, and Dependence
- Tell patients not to increase the dose of QUAZEPAM on their own, and to inform you if they believe the drug “does not work”.
### MEDICATION GUIDE
- Read the Medication Guide that comes with QUAZEPAM before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment.
- QUAZEPAM may cause serious side effects that you may not know are happening to you. These side effects include:
- sleepiness during the day
- not thinking clearly
- act strangely, confused, or upset
- “sleep-walking” or doing other activities when you are asleep like:
- eating
- talking
- having sex
- driving a car
- Call your healthcare provider right away if you find out that you have done any of the above activities after taking QUAZEPAM.
- QUAZEPAM is a prescription medicine used to treat certain types of insomnia including difficulty falling asleep, waking up often during the night, or waking up early in the morning.
- It is not known if QUAZEPAM is safe and effective in children.
- QUAZEPAM is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep QUAZEPAM in a safe place to prevent misuse and abuse. Selling or giving away QUAZEPAM may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.
- Do not take QUAZEPAM if you:
- are allergic to quazepam or any of the ingredients in QUAZEPAM. See the end of this Medication Guide for a complete list of ingredients in QUAZEPAM.
- have had an allergic reaction to other sleep medicines or sedatives such as benzodiazepines. Symptoms of a serious allergic reaction to quazepam can include:
- swelling of your face, lips, and throat that may cause difficulty breathing or swallowing
- nausea and vomiting
- have sleep apnea, snoring, breathing or lung problems
- Talk to your healthcare provider before taking this medicine if you have any of these conditions.
- QUAZEPAM may not be right for you. Before taking QUAZEPAM, tell your healthcare provider about all of your health conditions, including if you:
- have a history of depression, mental illness or, suicidal thoughts
- have a history of drug or alcohol abuse or addiction
- have lung disease or breathing problems
- are pregnant or plan to become pregnant. It is not known if QUAZEPAM can harm your unborn baby.
- are breastfeeding, or plan to breastfeed. QUAZEPAM can pass through your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take QUAZEPAM.
- Tell your healthcare provider about all of the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.
- Medicines can interact with each other, sometimes causing serious side effects. Do not take QUAZEPAM with other medicines that can make you sleepy unless your healthcare provider tells you to.
- Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.
- See “What is the most important information I should know about QUAZEPAM?”
- Take QUAZEPAM exactly as your healthcare providers tell you to take it.
- Do not stop taking QUAZEPAM without talking to your healthcare provider, drug withdrawal symptoms can happen.
- QUAZEPAM comes in 15 mg tablets. Your healthcare provider may start your QUAZEPAM dose at 7.5 mg which is half a tablet. Talk to your healthcare provider or pharmacist about your dose schedule.
- You should not drink alcohol while you are taking QUAZEPAM.
- Call your healthcare provider if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problem.
- If you take too much QUAZEPAM or overdose, get emergency treatment right away.
- QUAZEPAM may cause serious side effects, including:
- getting out of bed while not being fully awake and doing an activity that you do not know you are doing. See “What is the most important information I should know about QUAZEPAM?”
- abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions.
- memory loss
- severe allergic reactions. Symptoms include swelling of the tongue or throat, and trouble breathing. Get emergency medical help right away if you have these symptoms after taking QUAZEPAM.
- Call your healthcare provider right away if you have any of the above side effects or any other side effects that worry you while using QUAZEPAM.
- Common side effects of QUAZEPAM include:
- drowsiness
- headache
- feeling very tired
- dizziness
- dry mouth
- upset stomach
- After you stop taking a sleep medicine, you may have symptoms for the next 1 to 2 days such as:
- trouble sleeping
- nausea
- flushing
- lightheadedness
- uncontrolled crying
- vomiting
- stomach cramps
- panic attack
- nervousness
- stomach area pain
- Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
- These are not all the possible side effects of QUAZEPAM. Ask your healthcare provider or pharmacist for more information.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
- Store at room temperature between 68°F to 77° F (20°C to 25°C).
- Keep QUAZEPAM and all medicines out of the reach of children
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use QUAZEPAM for a condition for which it was not prescribed. Do not share QUAZEPAM with other people, even if they have the same symptoms that you have. It may harm them and it is against the law.
- This Medication Guide summarizes the most important information about QUAZEPAM. If you would like more information about QUAZEPAM, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about QUAZEPAM that is written for healthcare professionals.
- If you would like more information, go to or call Questcor Pharmaceuticals at 1-800-411-3065QUAZEPAM.
- Active Ingredient: quazepam
- Inactive Ingredients: cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.
- Distributed by Questcor Pharmaceuticals, Inc.
- Hayward, CA 94545 USA
- This Medication Guide has been approved by the U.S. Food and Drug Administration.
# Precautions with Alcohol
- Alcohol-Quazepam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Doral®
# Look-Alike Drug Names
There is limited information regarding Quazepam Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Quazepam
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]
# Disclaimer
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# Overview
Quazepam is a Benzodiazepine that is FDA approved for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Common adverse reactions include drowsiness, headache, fatigue, dizziness, dry mouth, dyspepsia.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- QUAZEPAM® (quazepam) is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of QUAZEPAM has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of QUAZEPAM has been established in chronic insomnia in a sleep lab (polysomnographic) study of 28 nights duration. Because insomnia is often transient and intermittent, the prolonged administration of QUAZEPAM Tablets is generally not necessary or recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered.
### Dosage
- Use the lowest dose effective for the patient, as important adverse effects of QUAZEPAM are dose related.
- The recommended initial dose is 7.5 mg. The 7.5 mg dose can be increased to 15 mg if necessary for efficacy.
- The 7.5 mg dose can be achieved by splitting the 15 mg tablet along the score line.
- Elderly and debilitated patients may be more sensitive to benzodiazepines.
### DOSAGE FORMS AND STRENGTHS
- Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (QUAZEPAM) on the other.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Quazepam in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Quazepam in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Quazepam in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Quazepam in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Quazepam in pediatric patients.
# Contraindications
- QUAZEPAM is contraindicated in patients with known hypersensitivity to quazepam or other benzodiazepines. Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of QUAZEPAM. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Patients who develop such reactions should not be rechallenged with QUAZEPAM.
- Contraindicated in patients with established or suspected sleep apnea, or with pulmonary insufficiency.
# Warnings
- QUAZEPAM is a central nervous system (CNS) depressant and can impair daytime function in some patients even when used as prescribed. Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam (i.e. less than formal psychomotor testing). While pharmacodynamic tolerance or adaptation to some adverse depressant effects of QUAZEPAM may develop, patients using QUAZEPAM should be cautioned against driving or engaging in other hazardous activities or activities requiring complete mental alertness.
- Additive effects occur with concomitant use of other CNS depressants (e.g., other benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use. Downward dose adjustment of QUAZEPAM and concomitant CNS depressants should be considered. The potential for adverse drug interactions continues for several days following discontinuation of QUAZEPAM, until serum levels of both active parent drug and psychoactive metabolites decline.
- Use of QUAZEPAM with other sedative-hypnotics is not recommended. Alcohol generally should not be used during treatment with QUAZEPAM. The risk of next-day psychomotor impairment is increased if QUAZEPAM is taken with less than a full night of sleep remaining (7- to 8 hours); if higher than the recommended dose is taken; if co-administered with other CNS depressants.
- A withdrawal syndrome similar to that from alcohol (e.g., convulsions, tremor, abdominal and muscle cramps, vomiting, and sweating) can occur following abrupt discontinuation of QUAZEPAM. The more severe withdrawal effects are usually limited to patients taking higher than recommended doses over an extended time. Abrupt discontinuation should be avoided in such patients, and the dose gradually tapered. Prescribers should monitor patients for tolerance, abuse, and dependence.
- Milder withdrawal symptoms (e.g., dysphoria and insomnia) can occur following abrupt discontinuation of benzodiazepines taken at therapeutic levels for short periods.
- Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative-hypnotic drugs.
- Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including QUAZEPAM. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis.
- Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with QUAZEPAM should not be rechallenged with the drug.
- Abnormal thinking and behavior changes have been reported in patients treated with sedative-hypnotics including QUAZEPAM. Some of these changes include decreased inhibition (e.g., aggressiveness and extroversion that seemed out of character), bizarre behavior, and depersonalization. Visual and auditory hallucinations have also been reported. Amnesia, and other neuro-psychiatric symptoms may occur.
- Paradoxical reactions such as stimulation, agitation, increased muscle spasticity, and sleep disturbances may occur unpredictably.
- Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake, with amnesia for the event) have been reported with use of sedative-hypnotics. These behaviors can occur with initial treatment or in patients previously tolerant of QUAZEPAM or other sedative-hypnotics. Although these behaviors can occur with use at therapeutic doses, risk is increased by higher doses or concomitant use of alcohol or other CNS depressants. Due to risk to the patient and community, QUAZEPAM should be discontinued if "sleep-driving" occurs.
- Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events.
- Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered.
# Adverse Reactions
## Clinical Trials Experience
- The following serious adverse reactions are discussed in greater detail in other sections of the label:
- CNS-depressant effects and next-day impairment
- Benzodiazepine withdrawal syndrome
- Abnormal thinking and behavior changes, and complex behaviors
- Worsening of depression
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- The table shows adverse reactions occurring at an incidence of 1% or greater in relatively short-duration, placebo-controlled clinical trials of QUAZEPAM. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in actual practice.
- A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.
## Postmarketing Experience
There is limited information regarding Quazepam Postmarketing Experience in the drug label.
# Drug Interactions
- Benzodiazepines, including QUAZEPAM, produce additive CNS depressant effects when co-administered with ethanol or other CNS depressants (e.g. psychotropic medications, anticonvulsants, antihistamines). Downward dose adjustment of QUAZEPAM and/or concomitant CNS depressants may be necessary because of additive effects.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- There are no adequate and well-controlled studies in pregnant women. Administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding. In addition, infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can development dependence, and subsequently withdrawal, during the postnatal period. Although administration of quazepam to pregnant animals did not indicate a risk for adverse effects on morphological development at clinically relevant doses, data for other benzodiazepines suggest the possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines. QUAZEPAM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Developmental toxicity studies of quazepam in mice at doses up to 400 times the human dose (15 mg) revealed no major drug-related malformations. Minor fetal skeletal variations that occurred were delayed ossification of the sternum, vertebrae, distal phalanges and supraoccipital bones, at doses approximately 70 and 400 times the human dose. A developmental toxicity study of quazepam in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Quazepam in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Quazepam during labor and delivery.
### Nursing Mothers
- Quazepam and its metabolites are excreted in human milk. Caution should be exercised when administering QUAZEPAM to a nursing woman.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- QUAZEPAM may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of QUAZEPAM and observed closely.
- Elderly and debilitated patients may be more sensitive to benzodiazepines, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- A double-blind controlled sleep laboratory study (N=30) compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.
### Gender
There is no FDA guidance on the use of Quazepam with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Quazepam with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Quazepam in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Quazepam in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Quazepam in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Quazepam in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
- Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam
- Prescribers should monitor patients for tolerance, abuse, and dependence.
- Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered.
# IV Compatibility
There is limited information regarding IV Compatibility of Quazepam in the drug label.
# Overdosage
- Contact a poison control center for up-to-date information on the management of benzodiazepine overdose.
- Manifestations of QUAZEPAM overdose include somnolence, confusion, and coma. General supportive measures should be employed, along with immediate gastric lavage. Dialysis is of limited value. Flumazenil may be useful, but can contribute to the appearance of neurological symptoms including convulsions. Hypotension may be treated by appropriate medical intervention. Animal experiments suggest that forced diuresis or hemodialysis are of little value in treating QUAZEPAM overdose. As with the management of intentional overdose with any drug, the possibility of multiple drug ingestion should be considered.
### DRUG ABUSE AND DEPENDENCE
- Quazepam is classified as a Schedule IV controlled substance by federal regulation.
- Addiction-prone individuals (e.g. history of drug addiction or alcoholism) should be under careful surveillance when receiving QUAZEPAM because of increased risk of abuse and dependence. Benzodiazepine withdrawal symptoms can occur following discontinuation of QUAZEPAM.
- Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.
- Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.
# Pharmacology
## Mechanism of Action
- Quazepam, like other central nervous system agents of the 1,4-benzodiazepine class, presumably exerts its effects by binding to stereo-specific receptors at several sites within the central nervous system (CNS). The exact mechanism of action is unknown.
## Structure
- QUAZEPAM contains quazepam, a trifluoroethyl benzodiazepine hypnotic agent, having the chemical name 7-chloro-5- (o-fluoro-phenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazepine-2-thione and the following structural formula:
- Quazepam has the empirical formula C17H11CIF4N2S, and a molecular weight of 386.8. It is a white crystalline compound, soluble in ethanol and insoluble in water. Each QUAZEPAM Tablet contains 15 mg of quazepam. The inactive ingredients for QUAZEPAM Tablets include cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Quazepam in the drug label.
## Pharmacokinetics
- Quazepam is rapidly (absorption half-life of about 30 minutes) and well absorbed from the gastrointestinal tract. The peak plasma concentration of quazepam is approximately 20 ng/mL after a 15 mg dose and occurs at about 2 hours.
- Quazepam, the active parent compound, is extensively metabolized in the liver; two of the plasma metabolites are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. All three compounds show CNS depressant activity.
- The degree of plasma protein binding for quazepam and its two major metabolites is greater than 95%.
- Following administration of 14C-quazepam, 31% of the dose appeared in the urine and 23% in the feces over five days; only trace amounts of unchanged drug were present in the urine.
- The mean elimination half-life of quazepam and 2-oxoquazepam is 39 hours and that of N-desalkyl-2-oxoquazepam is 73 hours. Steady-state levels of quazepam and 2-oxoquazepam are attained by the seventh daily dose and that of N-desalkyl-2-oxoquazepam by the thirteenth daily dose.
- Geriatrics: The pharmacokinetics of quazepam and 2-oxoquazepam in geriatric subjects are comparable to those seen in young adults; as with desalkyl metabolites of other benzodiazepines, the elimination half-life of N-desalkyl-2-oxoquazepam in geriatric patients is about twice that of young adults.
- Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.
## Nonclinical Toxicology
- Quazepam showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters.
- Quazepam was negative in the bacterial reverse mutation (Ames) assay and equivocal in the mouse lymphoma tk assay.
- Reproduction studies in mice conducted with quazepam at doses equal to 60 and 180 times the human dose of 15 mg produced slight reductions in fertility rate. Similar reductions in fertility rate have been reported in mice dosed with other benzodiazepines, and is believed to be related to the sedative effects of these drugs at high doses..
# Clinical Studies
- The effectiveness of QUAZEPAM was established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of QUAZEPAM was established in chronic insomnia in a sleep laboratory (polysomnographic) study of 28 nights duration.
- In the sleep laboratory study, QUAZEPAM significantly decreased sleep latency and total wake time, and significantly increased total sleep time and percent sleep time, for one or more nights. QUAZEPAM 15 mg was effective on the first night of administration. Sleep latency, total wake time and wake time after sleep onset were still decreased and percent sleep time was still increased for several nights after the drug was discontinued. Percent slow wave sleep was decreased, and REM sleep was essentially unchanged. No transient sleep disturbance, such as “rebound insomnia,” was observed after withdrawal of the drug in sleep laboratory studies in 12 patients using 15 mg doses.
- In outpatient studies, QUAZEPAM Tablets improved all subjective measures of sleep including sleep latency, duration of sleep, number of awakenings, occurrence of early morning awakening, and sleep quality. Some effects were evident on the first night of administration of QUAZEPAM (sleep latency, number of awakenings, and duration of sleep).
- A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be effective. Caution must be used in interpreting this data due to the small size of the study.
# How Supplied
- QUAZEPAM Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (QUAZEPAM) on the other.
## Storage
- Store QUAZEPAM® Tablets at controlled room temperature 20°-25°C (68°-77°F).
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
Package Label – Principal Display Panel – 15mg 100 Tablet Carton
100 tablets
QUAZEPAM (quazepam tablets, USP)
C-IV
15 mg Tablets
Provide a MEDICATION GUIDE each time this drug is dispensed to a patient. MEDICATION GUIDES are enclosed.
Rx only
### Ingredients and Appearance
# Patient Counseling Information
- See FDA-approved patient labeling (Medication Guide).
- Inform patients about the benefits and risks of QUAZEPAM, stressing the importance of use as directed. Assist patients in understanding the Medication Guide and instruct them to read it with each prescription refill.
- CNS depressant Effects and Next-Day Impairment
- Tell patients that QUAZEPAM can cause next-day impairment, even in the absence of symptoms. Caution patients against driving or engaging in other hazardous activities or activities requiring complete mental alertness when using QUAZEPAM. Tell patients that daytime impairment may persist for several days following discontinuation of QUAZEPAM.
- Withdrawal
- Instruct patients to contact you before stopping or decreasing the dose of QUAZEPAM, because withdrawal symptoms can occur.
- Abnormal thinking and behavior change
- Instruct patients that sedative hypnotics can cause abnormal thinking and behavior change, including “sleep-driving” and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop any of these symptoms.
- Severe Allergic Reactions
- Inform patients that severe allergic reactions can occur from QUAZEPAM. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if these occur.
- Suicide
- Tell patients that QUAZEPAM can worsen depression, and to immediately report any suicidal thoughts.
- Alcohol and other drugs
- Ask patients about alcohol consumption, medicines they are taking now, and drugs they may be taking without a prescription. Advise patients that alcohol generally should not be used during treatment with QUAZEPAM.
- Pregnancy
- Instruct patients to inform you if they are nursing or pregnant, or may become pregnant while taking QUAZEPAM.
- Tolerance, Abuse, and Dependence
- Tell patients not to increase the dose of QUAZEPAM on their own, and to inform you if they believe the drug “does not work”.
### MEDICATION GUIDE
- Read the Medication Guide that comes with QUAZEPAM before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment.
- QUAZEPAM may cause serious side effects that you may not know are happening to you. These side effects include:
- sleepiness during the day
- not thinking clearly
- act strangely, confused, or upset
- “sleep-walking” or doing other activities when you are asleep like:
- eating
- talking
- having sex
- driving a car
- Call your healthcare provider right away if you find out that you have done any of the above activities after taking QUAZEPAM.
- QUAZEPAM is a prescription medicine used to treat certain types of insomnia including difficulty falling asleep, waking up often during the night, or waking up early in the morning.
- It is not known if QUAZEPAM is safe and effective in children.
- QUAZEPAM is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep QUAZEPAM in a safe place to prevent misuse and abuse. Selling or giving away QUAZEPAM may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.
- Do not take QUAZEPAM if you:
- are allergic to quazepam or any of the ingredients in QUAZEPAM. See the end of this Medication Guide for a complete list of ingredients in QUAZEPAM.
- have had an allergic reaction to other sleep medicines or sedatives such as benzodiazepines. Symptoms of a serious allergic reaction to quazepam can include:
- swelling of your face, lips, and throat that may cause difficulty breathing or swallowing
- nausea and vomiting
- have sleep apnea, snoring, breathing or lung problems
- Talk to your healthcare provider before taking this medicine if you have any of these conditions.
- QUAZEPAM may not be right for you. Before taking QUAZEPAM, tell your healthcare provider about all of your health conditions, including if you:
- have a history of depression, mental illness or, suicidal thoughts
- have a history of drug or alcohol abuse or addiction
- have lung disease or breathing problems
- are pregnant or plan to become pregnant. It is not known if QUAZEPAM can harm your unborn baby.
- are breastfeeding, or plan to breastfeed. QUAZEPAM can pass through your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take QUAZEPAM.
- Tell your healthcare provider about all of the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.
- Medicines can interact with each other, sometimes causing serious side effects. Do not take QUAZEPAM with other medicines that can make you sleepy unless your healthcare provider tells you to.
- Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.
- See “What is the most important information I should know about QUAZEPAM?”
- Take QUAZEPAM exactly as your healthcare providers tell you to take it.
- Do not stop taking QUAZEPAM without talking to your healthcare provider, drug withdrawal symptoms can happen.
- QUAZEPAM comes in 15 mg tablets. Your healthcare provider may start your QUAZEPAM dose at 7.5 mg which is half a tablet. Talk to your healthcare provider or pharmacist about your dose schedule.
- You should not drink alcohol while you are taking QUAZEPAM.
- Call your healthcare provider if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problem.
- If you take too much QUAZEPAM or overdose, get emergency treatment right away.
- QUAZEPAM may cause serious side effects, including:
- getting out of bed while not being fully awake and doing an activity that you do not know you are doing. See “What is the most important information I should know about QUAZEPAM?”
- abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions.
- memory loss
- severe allergic reactions. Symptoms include swelling of the tongue or throat, and trouble breathing. Get emergency medical help right away if you have these symptoms after taking QUAZEPAM.
- Call your healthcare provider right away if you have any of the above side effects or any other side effects that worry you while using QUAZEPAM.
- Common side effects of QUAZEPAM include:
- drowsiness
- headache
- feeling very tired
- dizziness
- dry mouth
- upset stomach
- After you stop taking a sleep medicine, you may have symptoms for the next 1 to 2 days such as:
- trouble sleeping
- nausea
- flushing
- lightheadedness
- uncontrolled crying
- vomiting
- stomach cramps
- panic attack
- nervousness
- stomach area pain
- Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
- These are not all the possible side effects of QUAZEPAM. Ask your healthcare provider or pharmacist for more information.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
- Store at room temperature between 68°F to 77° F (20°C to 25°C).
- Keep QUAZEPAM and all medicines out of the reach of children
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use QUAZEPAM for a condition for which it was not prescribed. Do not share QUAZEPAM with other people, even if they have the same symptoms that you have. It may harm them and it is against the law.
- This Medication Guide summarizes the most important information about QUAZEPAM. If you would like more information about QUAZEPAM, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about QUAZEPAM that is written for healthcare professionals.
- If you would like more information, go to http://www.QUAZEPAMforsleep.com or call Questcor Pharmaceuticals at 1-800-411-3065QUAZEPAM.
- Active Ingredient: quazepam
- Inactive Ingredients: cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.
- Distributed by Questcor Pharmaceuticals, Inc.
- Hayward, CA 94545 USA
- This Medication Guide has been approved by the U.S. Food and Drug Administration.
# Precautions with Alcohol
- Alcohol-Quazepam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Doral®[1]
# Look-Alike Drug Names
There is limited information regarding Quazepam Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Doral | |
cbc602f609825f07b8f68dd3a44c259ebb6ddba7 | wikidoc | Dot blot | Dot blot
# Overview
A Dot blot (or Slot blot) is a technique in molecular biology used to detect biomolecules. It represents a simplification of the northern blot, Southern blot, or western blot methods. In a dot blot the biomolecules to be detected are not first separated by chromatography. Instead, a mixture containing the molecule to be detected is applied directly on a membrane as a dot. This is then followed by detection by either nucleotide probes (for a northern blot and Southern blot) or antibodies (for a western blot).
The technique offers significant savings in time, as chromatography or gel electrophoresis, and the complex blotting procedures for the gel are not required. However, it offers no information on the size of the target biomolecule. Furthermore, if two molecules of different sizes are detected, they will still appear as a single dot. Dot blots therefore can only confirm the presence or absence of a biomolecule or biomolecules which can be detected by the DNA probes or the antibody.
A radioactive sample can be hybridized to it allowing the researcher to detect variation between samples. The DNA is quantified and equal amounts are aliquoted into tubes in excess of the number of its targets in the samples, such as 10ug for a plasmid and 1ug for a PCR amplicon. These are denatured (NaOH and 95°C) and added to the wells where a vacuum sucks the water (with NaOH and NH4OAc) from underneath the membrane (nylon or nitrocellulose). | Dot blot
# Overview
A Dot blot (or Slot blot) is a technique in molecular biology used to detect biomolecules. It represents a simplification of the northern blot, Southern blot, or western blot methods. In a dot blot the biomolecules to be detected are not first separated by chromatography. Instead, a mixture containing the molecule to be detected is applied directly on a membrane as a dot. This is then followed by detection by either nucleotide probes (for a northern blot and Southern blot) or antibodies (for a western blot).
The technique offers significant savings in time, as chromatography or gel electrophoresis, and the complex blotting procedures for the gel are not required. However, it offers no information on the size of the target biomolecule. Furthermore, if two molecules of different sizes are detected, they will still appear as a single dot. Dot blots therefore can only confirm the presence or absence of a biomolecule or biomolecules which can be detected by the DNA probes or the antibody.
A radioactive sample can be hybridized to it allowing the researcher to detect variation between samples. The DNA is quantified and equal amounts are aliquoted into tubes in excess of the number of its targets in the samples, such as 10ug for a plasmid and 1ug for a PCR amplicon. These are denatured (NaOH and 95°C) and added to the wells where a vacuum sucks the water (with NaOH and NH4OAc) from underneath the membrane (nylon or nitrocellulose). | https://www.wikidoc.org/index.php/Dot_blot | |
4bf7c28e131f8afabc62f75b69a340acb81391da | wikidoc | Drooling | Drooling
Synonyms and keywords: ptyalism; sialorrhea; hypersalivation; Polysialia; Salivation excessive; Salivary hypersecretion; Sialism
# Overview
Drooling is the uncontrollable flow of saliva outside the mouth. It can occur in either some nervous system disorders or anatomic abnormalities of the oral cavity. Either the production of saliva is excessive, the musculature of the mouth which normally controls the oral opening, is weak and not functioning to the adequate strength to help keep the saliva inside or there is difficulty in swallowing.
Firstly we will discuss the production of saliva, which is carried out by the salivary glands. Upon receiving the excitatory stimulus from salivary nuclei present in the brain stem, saliva is produced, which occurs in response to the taste, and visual stimuli received from the tongue and other parts of the mouth. These are categorized into minor and major salivary glands. The major glands, which are most impressive are present in the base of the mouth, front of teeth, and in the cheeks, known as submandibular, parotid, and sublingual glands. So in total, there are 6 major glands that secrete saliva.
Isolated drooling is a common phenomenon in babies, often associated with teething, but it usually stops at around 15-36 months, when the baby develops salivary continence. Drooling in infants and young children may be exacerbated by upper respiratory infections and nasal allergies. The persistence of Sialorrhea after 4 years of age is therefore considered pathologic at times. It may persist due to hyper-salivation, or neurologic disorders like cerebral palsy, Parkinson’s disease, and amyotrophic lateral sclerosis, or as a side effect of medications. The most common cause of sialorrhea in children is Cerebral palsy whereas, in adults, Parkinson's disease is the most common cause. Other contributing factors for drooling are dental malocclusion, postural issues, and an inability to recognize salivary spills.
Drooling associated with fever or trouble swallowing may be a sign of a more serious disease including:
- Retropharyngeal abscess
- Peritonsillar abscess
- Tonsilitis
- Mononucleosis
- Strep throat
- Parkinson's disease
Sudden onset drooling may be an indication of poisoning (predominantly by pesticides) or a reaction to snake or insect venom. It can also be a side effect of numbed mouth from either orajel use in the dentist's office or medications. Some neurological problems also cause drooling. Excess intake of Capsaicin can lead to drooling as well, an example being the ingestion of particularly high Scoville Unit chili peppers.
Seasonal Allergies from pollen, trees, grass, mold, and weeds can also cause excessive saliva production and be a cause for drooling. Another form of ptyalism is associated with pregnancy, most common in women with a condition known as Hyperemesis Gravidarium, or uncontrollable and frequent nausea and vomiting during pregnancy which is far worse than typical "morning sickness". With Hyperemesis, ptyalism is a side-effect, which is a natural response to uncontrollable vomiting. With normal vomiting, salivary glands are stimulated to lubricate the esophagus and mouth to aid in expelling stomach contents. During a hyperemesis pregnancy, many women complain of excessive saliva and an inability to swallow this saliva. Some women note-having to carry around a "spitoon" or using a cup to spit. Swallowing their own saliva has been noted to gag and further nauseate the women making the hyperemesis that much worse.
There are several theories as to the causes of hyperemesis and related symptoms such as ptyalism. Many physicians are reluctant to treat hyperemesis since they don't see it as a true physiological illness but rather "in the patient's mind" . Many pregnant women who suffer end up terminating the pregnancy. Others refuse to carry another child. The most frequent act is preparing for the onset of hyperemesis if a subsequent pregnancy is expected.
Drooling is very bothersome, and can lead to many complications, both physical and psychosocial. Maceration and infection of the skin around the mouth, halitosis, dehydration, abnormalities in speech, and feeding difficulties are some of the complications. Also, drooling increases the chances of aspiration of saliva, food, or fluids into the lungs, especially with deranged reflex mechanisms like gagging or coughing. Moreover, people suffering from this face psychosocial troubles like isolation, education difficulties, increased level of dependency, decreased self-esteem, and difficult socialization. This overall, sialorrhea has a significant negative impact on the quality of life.
# Physiology
The major salivary glands in our oral cavity are the parotid, submandibular, and sublingual glands; amongst which the parotid glands are the largest. Saliva produced by these glands help in lubrication, and digestion of food, providing immunity, and maintaining of homeostasis in the human body. The salivary secretion is controlled mainly by the parasympathetic nervous system, with a minor contribution of sympathetic nervous system. The parasympathetic fibers originating from the pons and medulla, synapse in the otic and submandibular ganglia. The postganglionic fibers which originate from otic and submandibular ganglion regulate functions of parotid gland and submandibular/sublingual glands respectively. The sympathetic signals aid in contraction of muscle fibers surrounding the ducts of these glands, which result in the flow of saliva.
About 1.5 L of saliva is produced every day, 90% of which is carried out by the major salivary glands provide. Without stimulation, in the basal state, 70% of total saliva is produced by the submandibular and sublingual glands. Upon stimulation, the salivary secretion increases by five times. Chewing is an important source which causes stimulation of salivary glands. Salivary glands produce 2 types of saliva; thin and watery serous saliva, produced mainly by parotid glands and viscous thick saliva, produced predominantly by sublingual and submandibular glands. Excessive production of both can be a problema. Serous watery saliva consistently keeps on spilling from the side of the mouth, and viscous saliva being sticky, is harder to clear and often causes choking, which leads to panic.
# Causes
## Common Causes
- Retropharyngeal abscess
- Peritonsillar abscess
- Tonsilitis
- Mononucleosis
- Strep throat
- Parkinson's disease
- Epiglottitis
- Enlarged adenoids
- Dentures that are new or don't fit well
- Bell's palsy
- Cerebral Palsy
## Causes by Organ System
## Causes in Alphabetical Order
- Achillea ptarmica
- Actinomycosis
- Acute Gastritis or Gastric Ulcer
- Acute sinusitis
- All signs and symptoms
- Allergies
- Alveolar abscess
- Amaryllis poisoning
- Amyotrophic lateral sclerosis
- Angelman-Like Syndrome
- Ankylosis of the Temporomandibular Joint
- Antimony
- Aphthous Ulcers
- Arsenic poisoning
- Athetoid Cerebral Palsy
- Autism
- Balsam apple poisoning
- Bell's palsy
- Bilateral Facial Nerve Palsy
- Bone Lesions
- Boston Ivy poisoning
- Botulism
- Bromide
- Bulbar Paralysis
- Bush lily poisoning
- Buttercup poisoning
- Cantharides
- carbidopa-levodopa
- Cerebral Palsy
- Cerebrovascular Accident
- Chancre
- Chronic sinusitis
- clonazepam (Klonopin)
- Clozapine (Clozaril
- Copper
- Dementia
- Dental Caries
- Dental implant
- Dental malocclusion
- Dentures that are new or don't fit well
- Diphtheria
- Dog odor
- Donepezil
- Down syndrome
- Endoscopic foreign body retrieval
- Enlarged adenoids
- Epiglottitis
- Epilepsy and Ataxia Syndrome
- Epulis
- Esophageal atresia
- Esophageal food bolus obstruction
- Excessive starch intake
- Familial dysautonomia
- Foix-Chavany-Marie syndrome
- Foot-and-mouth disease
- Fragile X syndrome
- Galantamine
- Gastric distention or irritation
- Gastroesophageal Reflux
- Guillain-Barre syndrome
- Heartburn or GERD (reflux)
- Hyperemesis Gravidarum
- Hypoglossal Nerve palsy
- Hypotonia
- Infection in your mouth or throat
- Iodide
- Jaw Fracture or dislocation
- Jessamine poisoning
- Jonquil poisoning
- Juvenile Primary Lateral Sclerosis
- Liver disease
- Loratadine
- Macroglossia
- Marsh marigold poisoning
- Mayapple poisoning
- Mental retardation
- Mercury poisoning
- Mexican tea poisoning
- Microcephaly
- Mixed Cerebral Palsy
- Mobius syndrome
- Mononucleosis
- Motion sickness
- Mountain Laurel poisoning
- Multiple sclerosis
- Mumps
- Myasthenia Gravis
- Nicotine nasal spray
- Nicotine poisoning
- Oral chemical burns
- Oral infectious Lesions
- Oral suppurative lesions
- Organophosphate insecticide poisoning
- Pallidotomy
- Pancreatitis
- Parkinson disease
- Peritonsillar abscess
- Pilocarpine
- Poisoning (pesticides)
- Potassium Chlorate
- Pregnancy
- Procyclidine
- Pseudobulbar paralysis
- Pyridostigmine
- Rabies
- Radiation Therapy
- Rattlesnake bite
- Reaction to snake or insect venom
- Retropharyngeal Abscess
- Right parietal lobe syndrome related Alzheimer's disease
- Rolandic Epilepsy
- Sarcoma of the jaw
- Sarin
- Schwartz-Jampel Syndrome
- Sea urchin poisoning
- Segawa syndrome, autosomal recessive
- Sialorrhea
- Sinus infections
- Skunk cabbage poisoning
- Small Pox
- Smith-Magenis Syndrome
- Spastic paraplegia
- Split-leaf philodendron poisoning
- Stomatitis
- Strep throat
- Stroke
- Swollen adenoids
- Syphilis
- Tonic seizure
- Tonic-Clonic seizure
- Tonsillitis
- Tuberculosis
- Voriconazole
- X-linked Ataxia Telangiectasia
Achillea ptarmica
Alveolar abscess
Amaryllis poisoning
Amyotrophic lateral sclerosis
Angelman-Like Syndrome,
Ankylosis of the Temporomandibular Joint
Antimony
Aphthous Ulcers
Arsenic poisoning
Athetoid Cerebral Palsy
Autism
Balsam apple poisoning
Bell's palsy
Bilateral Facial Nerve Palsy
Bone Lesions
Boston Ivy poisoning
Botulism
Bromide
Bulbar Paralysis
Bush lily poisoning
Buttercup poisoning
Cantharides
carbidopa-levodopa
Cerebral Palsy
Cerebrovascular Accident
Chancre
Chronic sinusitis
clonazepam (Klonopin),
Clozapine (Clozaril)
Copper
Dementia
Dental Caries
Dental implant
Dental malocclusion
Dentures that are new or don't fit well
Diphtheria
Dog odor
Donepezil (patient information)
Down syndrome
Endoscopic foreign body retrieval
Enlarged adenoids
Epiglottitis
Epilepsy and Ataxia Syndrome
Epulis
Esophageal atresia
Esophageal food bolus obstruction
Excessive starch intake
Familial dysautonomia
Foix-Chavany-Marie syndrome
Foot-and-mouth disease
Fragile X syndrome
Galantamine
Gastric distention or irritation
Gastroesophageal Reflux
Guillain-Barré syndrome
Heartburn or GERD (reflux)
Hyperemesis Gravidarum
Hypoglossal Nerve palsy
Hypotonia
Infection in your mouth or throat
Iodide
Jaw Fracture or dislocation
Jessamine poisoning
Jonquil poisoning
Juvenile Primary Lateral Sclerosis
Liver disease
Loratadine
Macroglossia
Marsh marigold poisoning
Mayapple poisoning
Mental retardation
Mercury poisoning
Mexican tea poisoning
Microcephaly
Mixed Cerebral Palsy
Mobius syndrome
Mononucleosis
Motion sickness
Mountain Laurel poisoning
Multiple sclerosis
Mumps
Myasthenia Gravis
Nicotine nasal spray
Nicotine poisoning
Oral chemical burns
Oral infectious Lesions
Oral suppurative lesions
Organophosphate insecticide poisoning
Pallidotomy
Pancreatitis
Parkinson disease
Peritonsillar abscess
Pilocarpine
Poisoning (pesticides)
Potassium Chlorate
Pregnancy
Procyclidine
Pseudobulbar paralysis
Pyridostigmine
Rabies
Radiation Therapy
Rattlesnake bite
Reaction to snake or insect venom
Retropharyngeal Abscess
Right parietal lobe syndrome related Alzheimer's disease
Rolandic Epilepsy
Sarcoma of the jaw
Sarin
Schwartz-Jampel Syndrome
Sea urchin poisoning
Segawa syndrome, autosomal recessive
Sialorrhea
Sinus infections
Skunk cabbage poisoning
Small Pox
Smith-Magenis Syndrome
Spastic paraplegia
Split-leaf philodendron poisoning
Stomatitis
Strep throat
Stroke
Swollen adenoids
Syphilis
Tonic seizure
Tonic-Clonic seizure
Tonsillitis
Tuberculosis
Voriconazole
X-linked Ataxia Telangiectasia
Aconite
# Management
Sialorrhea is best managed by a team of primary health care providers, speech therapists, occupational therapists, dentists, orthodontists, neurologists, orthodontists, and otolaryngologists. Treatment options available for drooling can be either conservative, including just observation, some postural modifications, or biofeedback to more aggressive options like medication, radiation, or even surgical therapy. Anticholinergic medications, like glycopyrrolate or scopolamine, effectively reduce drooling, with certain side effects. The injection of botulinum toxin type A into the parotid and submandibular glands is another safe yet effective method of controlling drooling, but the effects fade in some months and we need to do repeat injections. Surgical interventions, like salivary gland excision, or duct ligation, and rerouting, are the most effective and permanent treatment options which greatly improve the quality of life of patients.
# Home care
Care for drooling due to teething includes good oral hygiene. Ice pops or other cold objects (e.g., frozen bagels) may be helpful. Care must be taken to avoid choking when a child uses any of these objects.
Drooling also is common in children with neurological disorders and those with undiagnosed developmental delay.
## The reason for excessive drooling seems to be related to;
- lack of awareness of the build-up of saliva in the mouth,
- infrequent swallowing,
- inefficient swallowing.
## Treatment of excessive drooling is related to these causes;
- increased awareness of the mouth and its functions,
- increased frequency of swallowing,
- increased swallowing skill.
# Sialorrhea
Sialorrhea is a condition characterized by the secretion of drool in the resting state. It is often the result of open-mouth posture from CNS depressants or sleeping on one's side. In the resting state, saliva may not build at the back of the throat, triggering the normal swallow reflex, thus allowing for the condition.
# Treatment
A comprehensive treatment plan incorporates several stages of care: correction of reversible causes, behavior modification, medical treatment, and surgical procedures. Atropine sulfate tablets are indicated to reduce salivation and may be prescribed by doctors in conjunction with behaviour modification strategies. In general, surgical procedures are considered after evaluation of non-invasive treatment options. | Drooling
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: ptyalism; sialorrhea; hypersalivation; Polysialia; Salivation excessive; Salivary hypersecretion; Sialism
# Overview
Drooling is the uncontrollable flow of saliva outside the mouth. It can occur in either some nervous system disorders or anatomic abnormalities of the oral cavity. Either the production of saliva is excessive, the musculature of the mouth which normally controls the oral opening, is weak and not functioning to the adequate strength to help keep the saliva inside or there is difficulty in swallowing.
Firstly we will discuss the production of saliva, which is carried out by the salivary glands. Upon receiving the excitatory stimulus from salivary nuclei present in the brain stem, saliva is produced, which occurs in response to the taste, and visual stimuli received from the tongue and other parts of the mouth. These are categorized into minor and major salivary glands. The major glands, which are most impressive are present in the base of the mouth, front of teeth, and in the cheeks, known as submandibular, parotid, and sublingual glands. So in total, there are 6 major glands that secrete saliva.
Isolated drooling is a common phenomenon in babies, often associated with teething, but it usually stops at around 15-36 months, when the baby develops salivary continence. Drooling in infants and young children may be exacerbated by upper respiratory infections and nasal allergies. The persistence of Sialorrhea after 4 years of age is therefore considered pathologic at times. It may persist due to hyper-salivation, or neurologic disorders like cerebral palsy, Parkinson’s disease, and amyotrophic lateral sclerosis, or as a side effect of medications. The most common cause of sialorrhea in children is Cerebral palsy whereas, in adults, Parkinson's disease is the most common cause. Other contributing factors for drooling are dental malocclusion, postural issues, and an inability to recognize salivary spills.
Drooling associated with fever or trouble swallowing may be a sign of a more serious disease including:
- Retropharyngeal abscess
- Peritonsillar abscess
- Tonsilitis
- Mononucleosis
- Strep throat
- Parkinson's disease
Sudden onset drooling may be an indication of poisoning (predominantly by pesticides) or a reaction to snake or insect venom. It can also be a side effect of numbed mouth from either orajel use in the dentist's office or medications. Some neurological problems also cause drooling. Excess intake of Capsaicin can lead to drooling as well, an example being the ingestion of particularly high Scoville Unit chili peppers.
Seasonal Allergies from pollen, trees, grass, mold, and weeds can also cause excessive saliva production and be a cause for drooling. Another form of ptyalism is associated with pregnancy, most common in women with a condition known as Hyperemesis Gravidarium, or uncontrollable and frequent nausea and vomiting during pregnancy which is far worse than typical "morning sickness". With Hyperemesis, ptyalism is a side-effect, which is a natural response to uncontrollable vomiting. With normal vomiting, salivary glands are stimulated to lubricate the esophagus and mouth to aid in expelling stomach contents. During a hyperemesis pregnancy, many women complain of excessive saliva and an inability to swallow this saliva. Some women note-having to carry around a "spitoon" or using a cup to spit. Swallowing their own saliva has been noted to gag and further nauseate the women making the hyperemesis that much worse.
There are several theories as to the causes of hyperemesis and related symptoms such as ptyalism. Many physicians are reluctant to treat hyperemesis since they don't see it as a true physiological illness but rather "in the patient's mind" [note: this is an old fashioned view and the medical community now considers hyperemesis as a real and serious physiological condition]. Many pregnant women who suffer end up terminating the pregnancy. Others refuse to carry another child. The most frequent act is preparing for the onset of hyperemesis if a subsequent pregnancy is expected.
Drooling is very bothersome, and can lead to many complications, both physical and psychosocial. Maceration and infection of the skin around the mouth, halitosis, dehydration, abnormalities in speech, and feeding difficulties are some of the complications. Also, drooling increases the chances of aspiration of saliva, food, or fluids into the lungs, especially with deranged reflex mechanisms like gagging or coughing. Moreover, people suffering from this face psychosocial troubles like isolation, education difficulties, increased level of dependency, decreased self-esteem, and difficult socialization. This overall, sialorrhea has a significant negative impact on the quality of life.
# Physiology
The major salivary glands in our oral cavity are the parotid, submandibular, and sublingual glands; amongst which the parotid glands are the largest. Saliva produced by these glands help in lubrication, and digestion of food, providing immunity, and maintaining of homeostasis in the human body. The salivary secretion is controlled mainly by the parasympathetic nervous system, with a minor contribution of sympathetic nervous system. The parasympathetic fibers originating from the pons and medulla, synapse in the otic and submandibular ganglia. The postganglionic fibers which originate from otic and submandibular ganglion regulate functions of parotid gland and submandibular/sublingual glands respectively. The sympathetic signals aid in contraction of muscle fibers surrounding the ducts of these glands, which result in the flow of saliva.
About 1.5 L of saliva is produced every day, 90% of which is carried out by the major salivary glands provide. Without stimulation, in the basal state, 70% of total saliva is produced by the submandibular and sublingual glands. Upon stimulation, the salivary secretion increases by five times. Chewing is an important source which causes stimulation of salivary glands. Salivary glands produce 2 types of saliva; thin and watery serous saliva, produced mainly by parotid glands and viscous thick saliva, produced predominantly by sublingual and submandibular glands. Excessive production of both can be a problema. Serous watery saliva consistently keeps on spilling from the side of the mouth, and viscous saliva being sticky, is harder to clear and often causes choking, which leads to panic.
# Causes
## Common Causes
- Retropharyngeal abscess
- Peritonsillar abscess
- Tonsilitis
- Mononucleosis
- Strep throat
- Parkinson's disease
- Epiglottitis
- Enlarged adenoids
- Dentures that are new or don't fit well
- Bell's palsy
- Cerebral Palsy
## Causes by Organ System
## Causes in Alphabetical Order
- Achillea ptarmica
- Actinomycosis
- Acute Gastritis or Gastric Ulcer
- Acute sinusitis
- All signs and symptoms
- Allergies
- Alveolar abscess
- Amaryllis poisoning
- Amyotrophic lateral sclerosis
- Angelman-Like Syndrome
- Ankylosis of the Temporomandibular Joint
- Antimony
- Aphthous Ulcers
- Arsenic poisoning
- Athetoid Cerebral Palsy
- Autism
- Balsam apple poisoning
- Bell's palsy
- Bilateral Facial Nerve Palsy
- Bone Lesions
- Boston Ivy poisoning
- Botulism
- Bromide
- Bulbar Paralysis
- Bush lily poisoning
- Buttercup poisoning
- Cantharides
- carbidopa-levodopa
- Cerebral Palsy
- Cerebrovascular Accident
- Chancre
- Chronic sinusitis
- clonazepam (Klonopin)
- Clozapine (Clozaril
- Copper
- Dementia
- Dental Caries
- Dental implant
- Dental malocclusion
- Dentures that are new or don't fit well
- Diphtheria
- Dog odor
- Donepezil
- Down syndrome
- Endoscopic foreign body retrieval
- Enlarged adenoids
- Epiglottitis
- Epilepsy and Ataxia Syndrome
- Epulis
- Esophageal atresia
- Esophageal food bolus obstruction
- Excessive starch intake
- Familial dysautonomia
- Foix-Chavany-Marie syndrome
- Foot-and-mouth disease
- Fragile X syndrome
- Galantamine
- Gastric distention or irritation
- Gastroesophageal Reflux
- Guillain-Barre syndrome
- Heartburn or GERD (reflux)
- Hyperemesis Gravidarum
- Hypoglossal Nerve palsy
- Hypotonia
- Infection in your mouth or throat
- Iodide
- Jaw Fracture or dislocation
- Jessamine poisoning
- Jonquil poisoning
- Juvenile Primary Lateral Sclerosis
- Liver disease
- Loratadine
- Macroglossia
- Marsh marigold poisoning
- Mayapple poisoning
- Mental retardation
- Mercury poisoning
- Mexican tea poisoning
- Microcephaly
- Mixed Cerebral Palsy
- Mobius syndrome
- Mononucleosis
- Motion sickness
- Mountain Laurel poisoning
- Multiple sclerosis
- Mumps
- Myasthenia Gravis
- Nicotine nasal spray
- Nicotine poisoning
- Oral chemical burns
- Oral infectious Lesions
- Oral suppurative lesions
- Organophosphate insecticide poisoning
- Pallidotomy
- Pancreatitis
- Parkinson disease
- Peritonsillar abscess
- Pilocarpine
- Poisoning (pesticides)
- Potassium Chlorate
- Pregnancy
- Procyclidine
- Pseudobulbar paralysis
- Pyridostigmine
- Rabies
- Radiation Therapy
- Rattlesnake bite
- Reaction to snake or insect venom
- Retropharyngeal Abscess
- Right parietal lobe syndrome related Alzheimer's disease
- Rolandic Epilepsy
- Sarcoma of the jaw
- Sarin
- Schwartz-Jampel Syndrome
- Sea urchin poisoning
- Segawa syndrome, autosomal recessive
- Sialorrhea
- Sinus infections
- Skunk cabbage poisoning
- Small Pox
- Smith-Magenis Syndrome
- Spastic paraplegia
- Split-leaf philodendron poisoning
- Stomatitis
- Strep throat
- Stroke
- Swollen adenoids
- Syphilis
- Tonic seizure
- Tonic-Clonic seizure
- Tonsillitis
- Tuberculosis
- Voriconazole
- X-linked Ataxia Telangiectasia
Achillea ptarmica
Alveolar abscess
Amaryllis poisoning
Amyotrophic lateral sclerosis
Angelman-Like Syndrome,
Ankylosis of the Temporomandibular Joint
Antimony
Aphthous Ulcers
Arsenic poisoning
Athetoid Cerebral Palsy
Autism
Balsam apple poisoning
Bell's palsy
Bilateral Facial Nerve Palsy
Bone Lesions
Boston Ivy poisoning
Botulism
Bromide
Bulbar Paralysis
Bush lily poisoning
Buttercup poisoning
Cantharides
carbidopa-levodopa
Cerebral Palsy
Cerebrovascular Accident
Chancre
Chronic sinusitis
clonazepam (Klonopin),
Clozapine (Clozaril)
Copper
Dementia
Dental Caries
Dental implant
Dental malocclusion
Dentures that are new or don't fit well
Diphtheria
Dog odor
Donepezil (patient information)
Down syndrome
Endoscopic foreign body retrieval
Enlarged adenoids
Epiglottitis
Epilepsy and Ataxia Syndrome
Epulis
Esophageal atresia
Esophageal food bolus obstruction
Excessive starch intake
Familial dysautonomia
Foix-Chavany-Marie syndrome
Foot-and-mouth disease
Fragile X syndrome
Galantamine
Gastric distention or irritation
Gastroesophageal Reflux
Guillain-Barré syndrome
Heartburn or GERD (reflux)
Hyperemesis Gravidarum
Hypoglossal Nerve palsy
Hypotonia
Infection in your mouth or throat
Iodide
Jaw Fracture or dislocation
Jessamine poisoning
Jonquil poisoning
Juvenile Primary Lateral Sclerosis
Liver disease
Loratadine
Macroglossia
Marsh marigold poisoning
Mayapple poisoning
Mental retardation
Mercury poisoning
Mexican tea poisoning
Microcephaly
Mixed Cerebral Palsy
Mobius syndrome
Mononucleosis
Motion sickness
Mountain Laurel poisoning
Multiple sclerosis
Mumps
Myasthenia Gravis
Nicotine nasal spray
Nicotine poisoning
Oral chemical burns
Oral infectious Lesions
Oral suppurative lesions
Organophosphate insecticide poisoning
Pallidotomy
Pancreatitis
Parkinson disease
Peritonsillar abscess
Pilocarpine
Poisoning (pesticides)
Potassium Chlorate
Pregnancy
Procyclidine
Pseudobulbar paralysis
Pyridostigmine
Rabies
Radiation Therapy
Rattlesnake bite
Reaction to snake or insect venom
Retropharyngeal Abscess
Right parietal lobe syndrome related Alzheimer's disease
Rolandic Epilepsy
Sarcoma of the jaw
Sarin
Schwartz-Jampel Syndrome
Sea urchin poisoning
Segawa syndrome, autosomal recessive
Sialorrhea
Sinus infections
Skunk cabbage poisoning
Small Pox
Smith-Magenis Syndrome
Spastic paraplegia
Split-leaf philodendron poisoning
Stomatitis
Strep throat
Stroke
Swollen adenoids
Syphilis
Tonic seizure
Tonic-Clonic seizure
Tonsillitis
Tuberculosis
Voriconazole
X-linked Ataxia Telangiectasia
Aconite
# Management
Sialorrhea is best managed by a team of primary health care providers, speech therapists, occupational therapists, dentists, orthodontists, neurologists, orthodontists, and otolaryngologists. Treatment options available for drooling can be either conservative, including just observation, some postural modifications, or biofeedback to more aggressive options like medication, radiation, or even surgical therapy. Anticholinergic medications, like glycopyrrolate or scopolamine, effectively reduce drooling, with certain side effects. The injection of botulinum toxin type A into the parotid and submandibular glands is another safe yet effective method of controlling drooling, but the effects fade in some months and we need to do repeat injections. Surgical interventions, like salivary gland excision, or duct ligation, and rerouting, are the most effective and permanent treatment options which greatly improve the quality of life of patients.
# Home care
Care for drooling due to teething includes good oral hygiene. Ice pops or other cold objects (e.g., frozen bagels) may be helpful. Care must be taken to avoid choking when a child uses any of these objects.
Drooling also is common in children with neurological disorders and those with undiagnosed developmental delay.
## The reason for excessive drooling seems to be related to;
- lack of awareness of the build-up of saliva in the mouth,
- infrequent swallowing,
- inefficient swallowing.
## Treatment of excessive drooling is related to these causes;
- increased awareness of the mouth and its functions,
- increased frequency of swallowing,
- increased swallowing skill.
# Sialorrhea
Sialorrhea is a condition characterized by the secretion of drool in the resting state. It is often the result of open-mouth posture from CNS depressants or sleeping on one's side. In the resting state, saliva may not build at the back of the throat, triggering the normal swallow reflex, thus allowing for the condition.
# Treatment
A comprehensive treatment plan incorporates several stages of care: correction of reversible causes, behavior modification, medical treatment, and surgical procedures. Atropine sulfate tablets are indicated to reduce salivation and may be prescribed by doctors in conjunction with behaviour modification strategies. In general, surgical procedures are considered after evaluation of non-invasive treatment options.
# External links
- NIH site on drooling
Template:Oral pathology
de:Hypersalivation
nl:Speekselvloed
fi:Kuolaaminen
Template:Jb1
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Drooling | |
0c51ebcd74baa3327f6f4fb859ddd6e2dde1dbaf | wikidoc | Dropwort | Dropwort
Dropwort (Filipendula vulgaris), also known as Fern-leaf Dropwort is a perennial herb of the family Rosaceae closely related to Meadowsweet. It is found in dry pastures across much of Europe and central and northern Asia. It has finely-cut, radical leaves, fern-like in appearance, and an erect stem 50-80 cm tall bearing a loose terminal inflorescence of small white flowers. The tiny flowers appear in dense clusters from late spring to mid summer.
This plant prefers full sun to partial shade. It is more tolerant of dry conditions than most other members of its genus.
# Cultivation and uses
A root decoction has been made from this plant to treat kidney ailments and is an expectorant. Propagation is by seed and the division of the creeping roots.
da:Knoldet Mjødurt
hsb:Dulkata smjetanka
nl:Knolspirea
sv:Brudbröd
uk:Гадючник шестипелюстковий | Dropwort
Dropwort (Filipendula vulgaris), also known as Fern-leaf Dropwort is a perennial herb of the family Rosaceae closely related to Meadowsweet. It is found in dry pastures across much of Europe and central and northern Asia. It has finely-cut, radical leaves, fern-like in appearance, and an erect stem 50-80 cm tall bearing a loose terminal inflorescence of small white flowers. The tiny flowers appear in dense clusters from late spring to mid summer.
This plant prefers full sun to partial shade. It is more tolerant of dry conditions than most other members of its genus.
## Cultivation and uses
A root decoction has been made from this plant to treat kidney ailments and is an expectorant. Propagation is by seed and the division of the creeping roots.
Template:Rosales-stub
da:Knoldet Mjødurt
hsb:Dulkata smjetanka
nl:Knolspirea
sv:Brudbröd
uk:Гадючник шестипелюстковий | https://www.wikidoc.org/index.php/Dropwort | |
b37ea09416c53302b8cc425988a6560abe16d9f5 | wikidoc | Drug use | Drug use
# Overview
Drugs can be used in many different ways, as detailed below.
# Medication
People can use drugs to relieve pain or discomfort or to cure or prevent disease. Not all medication is drugs however.
# Recreational drug use
Recreational drug use is the use of psychoactive drugs for recreational purposes rather than for work, medical or spiritual purposes, although the distinction is not always clear. At least one psychopharmacologist who has studied this field refers to it as the 'Fourth Drive,' arguing that the human instinct to seek mind-altering substances has so much force and persistence that it functions like the human drives for hunger, thirst and shelter.
# Responsible drug use
The concept of responsible drug use is that a person can use recreational drugs with reduced or eliminated risk of negatively affecting other parts of one's life or other peoples lives. Advocates of this idea point to the many well-known artists and intellectuals who have used drugs, experimentally or otherwise, with few detrimental effects on their lives. Critics argue that the drugs are escapist--and dangerous, unpredictable and sometimes addictive; thus predicating the idea of a responsible use of drugs as an idea, ultimately disputable upon debate.
# Gateway drug theory
The gateway drug theory is the belief that use of a lower classed drug can lead to the subsequent use of "harder", more dangerous drugs. The term is also used to describe introductory experiences to addictive substances. Some believe tobacco, alcohol, and marijuana are gateway drugs.
Some research suggests that serious drug abusers adopt an atypical drug use sequence with use of other drugs initiated before marijuana or alcohol.
There are many pharmacological similarities between various drugs of abuse. Individual social histories show that "hard" drug users do progress from one drug to another, but the reasons are not clear enough to generalise a gateway.
# Drug addiction
Drug addiction is a condition characterized by compulsive drug intake, craving and seeking, despite what the majority of society may perceive as the negative consequences associated with drug use.
# Drug abuse
Drug abuse has a wide range of definitions related to taking a psychoactive drug or performance enhancing drug for a non-therapeutic or non-medical effect. Some of the most commonly abused drugs include alcohol, amphetamines, barbiturates, benzodiazepines, cocaine, methaqualone, and opium alkaloids. Use of these drugs may lead to criminal penalty in addition to possible physical, social, and psychological harm, both strongly depending on local jurisdiction. Other definitions of drug abuse fall into four main categories: public health definitions, mass communication and vernacular usage, medical definitions, and political and criminal justice definitions. | Drug use
# Overview
Drugs can be used in many different ways, as detailed below.
# Medication
People can use drugs to relieve pain or discomfort or to cure or prevent disease. Not all medication is drugs however.
# Recreational drug use
Recreational drug use is the use of psychoactive drugs for recreational purposes rather than for work, medical or spiritual purposes, although the distinction is not always clear. At least one psychopharmacologist who has studied this field refers to it as the 'Fourth Drive,' arguing that the human instinct to seek mind-altering substances has so much force and persistence that it functions like the human drives for hunger, thirst and shelter.[1]
# Responsible drug use
The concept of responsible drug use is that a person can use recreational drugs with reduced or eliminated risk of negatively affecting other parts of one's life or other peoples lives. Advocates of this idea point to the many well-known artists and intellectuals who have used drugs, experimentally or otherwise, with few detrimental effects on their lives. Critics argue that the drugs are escapist--and dangerous, unpredictable and sometimes addictive; thus predicating the idea of a responsible use of drugs as an idea, ultimately disputable upon debate.
# Gateway drug theory
The gateway drug theory is the belief that use of a lower classed drug can lead to the subsequent use of "harder", more dangerous drugs.[2] The term is also used to describe introductory experiences to addictive substances. Some believe[3][4][5] tobacco, alcohol, and marijuana are gateway drugs.
Some research suggests that serious drug abusers adopt an atypical drug use sequence with use of other drugs initiated before marijuana or alcohol.[6]
There are many pharmacological similarities between various drugs of abuse. Individual social histories show that "hard" drug users do progress from one drug to another, but the reasons are not clear enough to generalise a gateway.[7]
# Drug addiction
Drug addiction is a condition characterized by compulsive drug intake, craving and seeking, despite what the majority of society may perceive as the negative consequences associated with drug use.[8]
# Drug abuse
Drug abuse has a wide range of definitions related to taking a psychoactive drug or performance enhancing drug for a non-therapeutic or non-medical effect. Some of the most commonly abused drugs include alcohol, amphetamines, barbiturates, benzodiazepines, cocaine, methaqualone, and opium alkaloids. Use of these drugs may lead to criminal penalty in addition to possible physical, social, and psychological harm, both strongly depending on local jurisdiction.[9] Other definitions of drug abuse fall into four main categories: public health definitions, mass communication and vernacular usage, medical definitions, and political and criminal justice definitions.[citation needed] | https://www.wikidoc.org/index.php/Drug/alcohol_effects | |
2edad1ec6b1c9396d5140699b14c64e95bc88a81 | wikidoc | Duodenum | Duodenum
# Overview
In anatomy of the digestive system, the duodenum is a hollow jointed tube connecting the stomach to the jejunum. It is the first and shortest part of the small intestine and it is where most chemical digestion takes place. It begins with the duodenal bulb and ends at the ligament of Treitz. The name duodenum is from the Latin duodenum digitorum, twelve fingers' breadths or inches.
# Function
The duodenum is largely responsible for the breakdown of food in the small intestine. Brunner's glands, which secrete mucus, are found in the duodenum. The duodenum wall is composed of a very thin layer of cells that form the muscularis mucosae. The duodenum is almost entirely retroperitoneal. The pH in the duodenum is approximately six.
# Sections
The duodenum is divided into four sections for the purposes of description. The first three sections form a "C" shape.
## First part
The first (superior) part began as a continuation of the duodenal end of the pylorus. From here it passes laterally (right), superiorly and posteriorly, for approximately 5 cm, before making a sharp curve inferiorly into the superior duodenal flexure (the end of the superior part). It is intraperitoneal.
## Second part
The second (descending) part of the duodenum begins at the superior duodenal flexure. It passes inferiorly to the lower border of vertebral body L3, before making a sharp turn medially into the inferior duodenal flexure (the end of the descending part).
The pancreatic duct and common bile duct enter the descending duodenum, commonly known together as the hepatopancreatic duct (or pancreatic duct in the United States), through the major duodenal papilla. This part of the duodenum also contains the minor duodenal papilla, the entrance for the accessory pancreatic duct. The junction between the embryological foregut and midgut lies just below the major duodenal papilla.
## Third part
The third (inferior/horizontal) part of the duodenum begins at the inferior duodenal flexure and passes transversely to the left, crossing the inferior vena cava, aorta and the vertebral column.
## Fourth part
The fourth (ascending) part passes superiorly, either anterior to, or to the right of, the aorta, until it reaches the inferior border of the body of the pancreas. Then, it curves anteriorly and terminates at the duodenojejunal flexure where it joins the jejunum. The duodenojejunal flexure is surrounded by a peritoneal fold containing muscle fibres: the ligament of Treitz.
# Additional images
- The celiac artery and its branches; the stomach has been raised and the peritoneum removed.
- Superior and inferior duodenal fossæ.
- Duodenojejunal fossa.
- Interior of the stomach.
- Section of duodenum of cat. X 60.
- The pancreas and duodenum from behind.
- Transverse section through the middle of the first lumbar vertebra, showing the relations of the pancreas.
- The pancreatic duct.
- Duodenum with amyloid deposition in lamina propria.
- Region of pancreas
- Stomach | Duodenum
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Template:Infobox Anatomy
In anatomy of the digestive system, the duodenum is a hollow jointed tube connecting the stomach to the jejunum. It is the first and shortest part of the small intestine and it is where most chemical digestion takes place. It begins with the duodenal bulb and ends at the ligament of Treitz. The name duodenum is from the Latin duodenum digitorum, twelve fingers' breadths or inches.
# Function
The duodenum is largely responsible for the breakdown of food in the small intestine. Brunner's glands, which secrete mucus, are found in the duodenum. The duodenum wall is composed of a very thin layer of cells that form the muscularis mucosae. The duodenum is almost entirely retroperitoneal. The pH in the duodenum is approximately six.
# Sections
The duodenum is divided into four sections for the purposes of description. The first three sections form a "C" shape.
## First part
The first (superior) part began as a continuation of the duodenal end of the pylorus. From here it passes laterally (right), superiorly and posteriorly, for approximately 5 cm, before making a sharp curve inferiorly into the superior duodenal flexure (the end of the superior part). It is intraperitoneal.
## Second part
The second (descending) part of the duodenum begins at the superior duodenal flexure. It passes inferiorly to the lower border of vertebral body L3, before making a sharp turn medially into the inferior duodenal flexure (the end of the descending part).
The pancreatic duct and common bile duct enter the descending duodenum, commonly known together as the hepatopancreatic duct (or pancreatic duct in the United States), through the major duodenal papilla. This part of the duodenum also contains the minor duodenal papilla, the entrance for the accessory pancreatic duct. The junction between the embryological foregut and midgut lies just below the major duodenal papilla.
## Third part
The third (inferior/horizontal) part of the duodenum begins at the inferior duodenal flexure and passes transversely to the left, crossing the inferior vena cava, aorta and the vertebral column.
## Fourth part
The fourth (ascending) part passes superiorly, either anterior to, or to the right of, the aorta, until it reaches the inferior border of the body of the pancreas. Then, it curves anteriorly and terminates at the duodenojejunal flexure where it joins the jejunum. The duodenojejunal flexure is surrounded by a peritoneal fold containing muscle fibres: the ligament of Treitz.
# Additional images
- The celiac artery and its branches; the stomach has been raised and the peritoneum removed.
- Superior and inferior duodenal fossæ.
- Duodenojejunal fossa.
- Interior of the stomach.
- Section of duodenum of cat. X 60.
- The pancreas and duodenum from behind.
- Transverse section through the middle of the first lumbar vertebra, showing the relations of the pancreas.
- The pancreatic duct.
- Duodenum with amyloid deposition in lamina propria.
- Region of pancreas
- Stomach | https://www.wikidoc.org/index.php/Duodenal | |
b1c0a420a43029bf797af60cc787a40d659cd1cb | wikidoc | Dwarfism | Dwarfism
Dwarfism refers to a condition of extreme small size of a person, animal, or plant. Any type of marked human smallness could be termed dwarfism in older popular and medical usage. The term as related to human beings (the major subject of this article) is often used to refer specifically to those forms of extreme shortness characterized by disproportion of body parts, typically due to an inheritable disorder in bone or cartilage development.
Forms of extreme shortness characterized by proportional body parts usually have a hormonal or nutritional cause. An example is growth hormone deficiency, once known as "pituitary dwarfism".
The Little People of America (LPA) defines dwarfism as a medical or genetic condition that usually results in an adult height of 4'10" (147 cm) or shorter.
# Types of dwarfism
Types of dwarfism are often clinically distinguished by the predominant segment of the limbs that is short:
- rhizomelic = root, e.g. bones of upper arm or thigh
- mesomelic = middle, e.g. bones of forearm or lower leg
- acromelic = end, e.g. bones of hands and feet.
When the cause of dwarfism is understood, it may be classified according to one of hundreds of names, which are usually permutations of the following roots:
- chondro = of cartilage
- osteo = of bone
- spondylo = of the vertebrae
- plasia = form
- trophy = growth
Examples include achondroplasia, osseous dysplasia, chondrodystrophy, and osteochondrodystrophy.
The most recognizable and most common form of dwarfism is achondroplasia, which produces rhizomelic short limbs, increased spinal curvature, and distortion of skull growth. It accounts for 70% of dwarfism cases. Other relatively common types include spondyloepiphyseal dysplasia congenita (SED), diastrophic dysplasia, pseudoachondroplasia, hypochondroplasia, and osteogenesis imperfecta (OI). Severe shortness with skeletal distortion also occurs in several of the mucopolysaccharidoses and other storage diseases.
The average adult height of male and female dwarfism sufferers are 132cm and 123cm respectively. The average weight of an adult may range from 100 to 150 pounds (45-68 kg).
# Diagnosis
Unusually short stature for a child's age is usually what brings the child to medical attention. Skeletal dysplasia ("dwarfism") is usually suspected because of obvious physical features (e.g., unusual configuration of face or shape of skull), because of an obviously affected parent, or because body measurements (arm span, upper to lower segment ratio) indicate disproportion. Bone x-rays are often the key to diagnosis of a specific skeletal dysplasia, but they are not the key diagnosis. Most children with suspected skeletal dysplasias will be referred to a genetics clinic for diagnostic confirmation and genetic counselling. (See External links, below, for a list of American referral centers with special expertise in skeletal dysplasias.) In the last decade, genetic tests for some of the specific disorders have become available.
During the initial medical evaluation for shortness, the absence of disproportion and the other clues above usually indicates other causes than bone dysplasias. Extreme shortness with completely normal proportions sometimes indicates growth hormone deficiency (pituitary dwarfism).
Short stature alone, in the absence of any other abnormalities, may simply be genetic, particularly if a person is born into a family of people who are relatively short.
# Problems associated with dwarfism
The principal adverse effects of dwarfism can be divided into the physical and the social.
Physical effects of malformed bones vary according to the specific disease. Many involve pain resulting from joint damage from abnormal bone alignment, or from nerve compression (e.g, spinal stenosis).. Early degenerative joint disease, exaggerated lordosis or scoliosis, and constriction of spinal cord or nerve roots can cause pain and disability. Reduced thoracic size can restrict lung growth and reduce pulmonary function. Some forms of dwarfism are associated with disordered function of other organs, such as the brain or liver, sometimes severely enough to be more disabling than the abnormal bone growth.
The psychosocial disadvantages may be more distressing than the physical symptoms, especially in childhood and adolescence, but people with dwarfism vary greatly in the degree to which social participation and emotional health are affected.
- Social prejudice against extreme shortness may reduce social and marital opportunities. Template:Seealso
- Numerous studies have demonstrated reduced employment opportunities. Severe shortness is associated with lower income.
- Self-esteem may be reduced and family relationships affected
- Extreme shortness (in the low 2–3 foot range) can interfere with ordinary activities of daily living, like driving or even using countertops built for taller people.
# Treatment and support
As the genetic defects of most forms of dwarfism due to bone dysplasia cannot be corrected, therapeutic interventions are typically aimed at (1) preventing or reducing pain or physical disability, (2) increasing adult height, or (3) mitigating psychosocial stresses and enhancing social adaptation.
Pain and disability may be ameliorated by physical therapy, by braces or other orthotic devices, or by surgical procedures.
The only simple interventions that increase perceived adult height are dress enhancements such as shoe lifts or hairstyle. Growth hormone is rarely used for shortness due to bone dysplasias, as the height benefit is typically small (less than 5 cm) and the cost high. The most effective means of increasing adult height by several inches is limb-lengthening surgery, though availability is limited and cost is high in terms of dollars, discomfort, and interruption of life. Most people with dwarfism do not avail themselves of this, and it remains controversial. For other types of dwarfism, surgical treatment is not possible.
# Dwarfism in non-Western cultures
In the Talmud, it is said that the second born son of the Egyptian Pharaoh of the Bible was a dwarf.
# In popular culture and the arts
When depicted in art, literature, or movies, dwarfs are rarely depicted as "regular people who are very short" but often as a species apart. Novelists, artists, and moviemakers attach special moral or aesthetic significance to the "apartness" or the misshapenness.
Artistic representations of dwarfism can be found on Greek vases and other ancient artifacts, including ancient Egyptian art. Documentation of dwarfs can also be found on European paintings and many pictures. Many European paintings (especially Spanish) of the 16th–19th centuries depict dwarfs by themselves or with others.
Several novels have treated dwarfism as a major theme, although not necessarily realistically:
- The Tin Drum (Die Blechtrommel) by Günter Grass
- Stones from the River by Ursula Hegi
- The Dwarf by Pär Lagerkvist
- A Prayer for Owen Meany by John Irving
- A Son of the Circus by John Irving
- "Hop-Frog, or The Eight Chained Ourang-Outangs" by Edgar Allan Poe
- Maybe the Moon by Armistead Maupin
- Swords and Crowns and Rings by Ruth Park
- Tale of the Wind by Kay Nolte Smith
- Memoir of a Dwarf in the Sun King's Court by Paul Weidner
- The Eye of Night by Pauline Alama
- Mendel's Dwarf by Simon Mawer
- Cat's Cradle by Kurt Vonnegut
- A Song of Ice and Fire by George R.R. Martin
Leslie Fiedler's Freaks: Myths and Images of the Secret Self (1979) explored the value of differentness of "freaks" to "normal" people, lamenting medical treatment for reducing the number of picturesquely different people around.
Several 20th and 21st century movies & TV shows have addressed the topic or made much use of dwarfs:
- Freaks (1932)
- The Terror of Tiny Town (1938)
- The Wizard of Oz (1939)
- Even Dwarfs Started Small (Auch Zwerge haben klein angefangen) (1970)
- Willy Wonka & the Chocolate Factory (1971)
- The Man With The Golden Gun (1974)
- Time Bandits (1981)
- Under the Rainbow (1981)
- Willow (1988)
- Leprechaun (film) (1992)
- Austin Powers: The Spy Who Shagged Me (1999)
- Austin Powers in Goldmember (2002)
- Monster Garage (2002-2006)
- The Station Agent (2003)
- Tiptoes (2003)
- Little People, Big World (2006) – Reality TV series following the daily lives of a family with two dwarf parents and one dwarf child (as well as three other children of average height)
- The Benchwarmers (2006)
The actor and stunt man Verne Troyer has become famous playing the character "Mini-Me" in two Austin Powers movies, as has fellow stuntman and Jackass castmember, Jason "Wee-Man" Acuña .
The 1960s television series The Wild Wild West featured a dwarf, Michael Dunn, as the recurring character Dr. Miguelito Loveless, the brilliant but insane arch-enemy of Secret Service agents James West and Artemus Gordon.
In the mid-1970's, Sid and Marty Krofft built an indoor theme park in Atlanta, Georgia called The World of Sid and Marty Krofft. This had a live stage production that was at that time the largest gathering of "little people" since the filming of The Wizard of Oz in 1937-38 as well as being the largest indoor theme park built to that time. The facility that was built to house this theme park is today the studios of CNN, the Cable News Network, and CNN Headline News.
In the 1990s, the immensely popular series Seinfeld featured a dwarf character, Mickey Abbott, in seven episodes; Mickey was played by actor Danny Woodburn. He once got into a fight with six-foot-plus Kramer. In one episode, he was ostracized by his dwarf peers for using lifts in his shoes to make him look taller.
From 1999 until 2003, the popular television series The Man Show featured dwarfs in many of their segments. They once claimed to be "the world's largest employer of midgets".
In Mind of Mencia, one of the main characters is a dwarf named Brad Williams. Brad is a comedian who tours with Carlos Mencia as his opening act.
In Monster Garage, Chris "Body Drop" Artiaga made his debut as a contestant in episode 'Ramp Rage', but later became parts runner for the series. In addition, there are 2 episodes featuring all-dwarf build teams.
In George R.R. Martin's A Song of Ice and Fire series, one of the main characters, Tyrion Lannister, is a dwarf. Though a brilliant and well-read man (some would say genius), he struggles with acceptance by "normal" people, who pejoratively refer to him as "the Imp," or "half-man". This is especially true of his father, Lord Tywin Lannister, who holds Tyrion in contempt, especially when compared to Tyrion's handsome, talented older brother Jaime, and Jaime's equally beautiful and talented twin sister, Cersei. Tyrion often wonders if any woman could ever truly love him in spite of his condition.
Johnny Roventini was a dwarf bellboy in a New York City hotel when he was paid $1 to "Call for Phillip Morris", unknowingly beginning his 40-year career as an advertising icon in radio, television, and print media. | Dwarfism
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:DiseaseDisorder infobox
Dwarfism refers to a condition of extreme small size of a person, animal, or plant. Any type of marked human smallness could be termed dwarfism in older popular and medical usage. The term as related to human beings (the major subject of this article) is often used to refer specifically to those forms of extreme shortness characterized by disproportion of body parts, typically due to an inheritable disorder in bone or cartilage development.
Forms of extreme shortness characterized by proportional body parts usually have a hormonal or nutritional cause. An example is growth hormone deficiency, once known as "pituitary dwarfism".
The Little People of America (LPA) defines dwarfism as a medical or genetic condition that usually results in an adult height of 4'10" (147 cm) or shorter.[1]
Template:Wiktionarypar2
# Types of dwarfism
Types of dwarfism are often clinically distinguished by the predominant segment of the limbs that is short:
- rhizomelic = root, e.g. bones of upper arm or thigh
- mesomelic = middle, e.g. bones of forearm or lower leg
- acromelic = end, e.g. bones of hands and feet.
When the cause of dwarfism is understood, it may be classified according to one of hundreds of names, which are usually permutations of the following roots:
- chondro = of cartilage
- osteo = of bone
- spondylo = of the vertebrae
- plasia = form
- trophy = growth
Examples include achondroplasia, osseous dysplasia, chondrodystrophy, and osteochondrodystrophy.[2]
The most recognizable and most common form of dwarfism is achondroplasia, which produces rhizomelic short limbs, increased spinal curvature, and distortion of skull growth. It accounts for 70% of dwarfism cases. Other relatively common types include spondyloepiphyseal dysplasia congenita (SED), diastrophic dysplasia, pseudoachondroplasia, hypochondroplasia, and osteogenesis imperfecta (OI). Severe shortness with skeletal distortion also occurs in several of the mucopolysaccharidoses and other storage diseases.
The average adult height of male and female dwarfism sufferers are 132cm and 123cm respectively. The average weight of an adult may range from 100 to 150 pounds (45-68 kg).
# Diagnosis
Unusually short stature for a child's age is usually what brings the child to medical attention. Skeletal dysplasia ("dwarfism") is usually suspected because of obvious physical features (e.g., unusual configuration of face or shape of skull), because of an obviously affected parent, or because body measurements (arm span, upper to lower segment ratio) indicate disproportion. Bone x-rays are often the key to diagnosis of a specific skeletal dysplasia, but they are not the key diagnosis. Most children with suspected skeletal dysplasias will be referred to a genetics clinic for diagnostic confirmation and genetic counselling. (See External links, below, for a list of American referral centers with special expertise in skeletal dysplasias.) In the last decade, genetic tests for some of the specific disorders have become available.
During the initial medical evaluation for shortness, the absence of disproportion and the other clues above usually indicates other causes than bone dysplasias. Extreme shortness with completely normal proportions sometimes indicates growth hormone deficiency (pituitary dwarfism).
Short stature alone, in the absence of any other abnormalities, may simply be genetic, particularly if a person is born into a family of people who are relatively short.
# Problems associated with dwarfism
The principal adverse effects of dwarfism can be divided into the physical and the social.
Physical effects of malformed bones vary according to the specific disease. Many involve pain resulting from joint damage from abnormal bone alignment, or from nerve compression (e.g, spinal stenosis).[1]. Early degenerative joint disease, exaggerated lordosis or scoliosis, and constriction of spinal cord or nerve roots can cause pain and disability. Reduced thoracic size can restrict lung growth and reduce pulmonary function. Some forms of dwarfism are associated with disordered function of other organs, such as the brain or liver, sometimes severely enough to be more disabling than the abnormal bone growth.
The psychosocial disadvantages may be more distressing than the physical symptoms, especially in childhood and adolescence, but people with dwarfism vary greatly in the degree to which social participation and emotional health are affected.
- Social prejudice against extreme shortness may reduce social and marital opportunities. Template:Seealso
- Numerous studies have demonstrated reduced employment opportunities. Severe shortness is associated with lower income.
- Self-esteem may be reduced and family relationships affected
- Extreme shortness (in the low 2–3 foot [60–90 cm] range) can interfere with ordinary activities of daily living, like driving or even using countertops built for taller people.
# Treatment and support
As the genetic defects of most forms of dwarfism due to bone dysplasia cannot be corrected, therapeutic interventions are typically aimed at (1) preventing or reducing pain or physical disability, (2) increasing adult height, or (3) mitigating psychosocial stresses and enhancing social adaptation.
Pain and disability may be ameliorated by physical therapy, by braces or other orthotic devices, or by surgical procedures.
The only simple interventions that increase perceived adult height are dress enhancements such as shoe lifts or hairstyle. Growth hormone is rarely used for shortness due to bone dysplasias, as the height benefit is typically small (less than 5 cm) and the cost high. The most effective means of increasing adult height by several inches is limb-lengthening surgery, though availability is limited and cost is high in terms of dollars, discomfort, and interruption of life. Most people with dwarfism do not avail themselves of this, and it remains controversial.[1] For other types of dwarfism, surgical treatment is not possible.
# Dwarfism in non-Western cultures
In the Talmud, it is said that the second born son of the Egyptian Pharaoh of the Bible was a dwarf.[2]
# In popular culture and the arts
Template:Cleanup-laundry
When depicted in art, literature, or movies, dwarfs are rarely depicted as "regular people who are very short" but often as a species apart. Novelists, artists, and moviemakers attach special moral or aesthetic significance to the "apartness" or the misshapenness.
Artistic representations of dwarfism can be found on Greek vases and other ancient artifacts, including ancient Egyptian art. Documentation of dwarfs can also be found on European paintings and many pictures. Many European paintings (especially Spanish) of the 16th–19th centuries depict dwarfs by themselves or with others.
Several novels have treated dwarfism as a major theme, although not necessarily realistically:
- The Tin Drum (Die Blechtrommel) by Günter Grass
- Stones from the River by Ursula Hegi
- The Dwarf by Pär Lagerkvist
- A Prayer for Owen Meany by John Irving
- A Son of the Circus by John Irving
- "Hop-Frog, or The Eight Chained Ourang-Outangs" by Edgar Allan Poe
- Maybe the Moon by Armistead Maupin
- Swords and Crowns and Rings by Ruth Park
- Tale of the Wind by Kay Nolte Smith
- Memoir of a Dwarf in the Sun King's Court by Paul Weidner
- The Eye of Night by Pauline Alama
- Mendel's Dwarf by Simon Mawer
- Cat's Cradle by Kurt Vonnegut
- A Song of Ice and Fire by George R.R. Martin
Leslie Fiedler's Freaks: Myths and Images of the Secret Self (1979) explored the value of differentness of "freaks" to "normal" people, lamenting medical treatment for reducing the number of picturesquely different people around.
Several 20th and 21st century movies & TV shows have addressed the topic or made much use of dwarfs:
- Freaks (1932)
- The Terror of Tiny Town (1938)
- The Wizard of Oz (1939)
- Even Dwarfs Started Small (Auch Zwerge haben klein angefangen) (1970)
- Willy Wonka & the Chocolate Factory (1971)
- The Man With The Golden Gun (1974)
- Time Bandits (1981)
- Under the Rainbow (1981)
- Willow (1988)
- Leprechaun (film) (1992)
- Austin Powers: The Spy Who Shagged Me (1999)
- Austin Powers in Goldmember (2002)
- Monster Garage (2002-2006)
- The Station Agent (2003)
- Tiptoes (2003)
- Little People, Big World (2006) – Reality TV series following the daily lives of a family with two dwarf parents and one dwarf child (as well as three other children of average height)
- The Benchwarmers (2006)
The actor and stunt man Verne Troyer has become famous playing the character "Mini-Me" in two Austin Powers movies, as has fellow stuntman and Jackass castmember, Jason "Wee-Man" Acuña .
The 1960s television series The Wild Wild West featured a dwarf, Michael Dunn, as the recurring character Dr. Miguelito Loveless, the brilliant but insane arch-enemy of Secret Service agents James West and Artemus Gordon.
In the mid-1970's, Sid and Marty Krofft built an indoor theme park in Atlanta, Georgia called The World of Sid and Marty Krofft. This had a live stage production that was at that time the largest gathering of "little people" since the filming of The Wizard of Oz in 1937-38 as well as being the largest indoor theme park built to that time. The facility that was built to house this theme park is today the studios of CNN, the Cable News Network, and CNN Headline News.
In the 1990s, the immensely popular series Seinfeld featured a dwarf character, Mickey Abbott, in seven episodes; Mickey was played by actor Danny Woodburn. He once got into a fight with six-foot-plus Kramer. In one episode, he was ostracized by his dwarf peers for using lifts in his shoes to make him look taller.
From 1999 until 2003, the popular television series The Man Show featured dwarfs in many of their segments. They once claimed to be "the world's largest employer of midgets".
In Mind of Mencia, one of the main characters is a dwarf named Brad Williams. Brad is a comedian who tours with Carlos Mencia as his opening act.
In Monster Garage, Chris "Body Drop" Artiaga made his debut as a contestant in episode 'Ramp Rage', but later became parts runner for the series. In addition, there are 2 episodes featuring all-dwarf build teams.
In George R.R. Martin's A Song of Ice and Fire series, one of the main characters, Tyrion Lannister, is a dwarf. Though a brilliant and well-read man (some would say genius), he struggles with acceptance by "normal" people, who pejoratively refer to him as "the Imp," or "half-man". This is especially true of his father, Lord Tywin Lannister, who holds Tyrion in contempt, especially when compared to Tyrion's handsome, talented older brother Jaime, and Jaime's equally beautiful and talented twin sister, Cersei. Tyrion often wonders if any woman could ever truly love him in spite of his condition.
Johnny Roventini was a dwarf bellboy in a New York City hotel when he was paid $1 to "Call for Phillip Morris", unknowingly beginning his 40-year career as an advertising icon in radio, television, and print media. | https://www.wikidoc.org/index.php/Dwarfism | |
9156df404f71e15eadc6abc6469907f60951b2a7 | wikidoc | Dynactin | Dynactin
# Overview
Dynactin or Dynein activator complex is a multi-subunit protein found in eukaryotic cells that aids in bidirectional intracellular organelle transport by binding to dynein and Kinesin II and linking them to the organelles to be transported.
# Structure and mechanism of action
Dynactin consists of many subunits of which the p150Glued doublet (encoded by the DCTN1 gene) is the largest and has been found to be essential for function. This structure of dynactin is highly conserved in vertebrates. There are three isoforms encoded by a single gene.
Dynactin interacts with dynein directly by the binding of dynein intermediate chains with the p150 (glued homolog) doublet.
# Functions
Dynactin is often essential for dynein activity and can be thought of as a "dynein receptor" that modulates binding of dynein to cell organelles which are to be transported along microtubules.
Dynactin is involved in various processes like chromosome alignment and spindle organization in cell division, maintaining nuclear position in addition to transport of various organelles in the cytoplasm.
Dynactin also links Kinesin II to organelles. | Dynactin
# Overview
Dynactin or Dynein activator complex is a multi-subunit protein found in eukaryotic cells that aids in bidirectional intracellular organelle transport by binding to dynein and Kinesin II and linking them to the organelles to be transported.[1][2]
# Structure and mechanism of action
Dynactin consists of many subunits of which the p150Glued doublet (encoded by the DCTN1 gene) is the largest and has been found to be essential for function. [1] This structure of dynactin is highly conserved in vertebrates. There are three isoforms encoded by a single gene.[3]
Dynactin interacts with dynein directly by the binding of dynein intermediate chains with the p150 (glued homolog) doublet.[4]
# Functions
Dynactin is often essential for dynein activity[1] and can be thought of as a "dynein receptor"[4] that modulates binding of dynein to cell organelles which are to be transported along microtubules.[5]
Dynactin is involved in various processes like chromosome alignment and spindle organization[5] in cell division,[6] maintaining nuclear position[7] in addition to transport of various organelles in the cytoplasm.
Dynactin also links Kinesin II to organelles. | https://www.wikidoc.org/index.php/Dynactin | |
9e941937794c969289027029cdc3e4e503ec062b | wikidoc | Dyskerin | Dyskerin
H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.
This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.
# Clinical significance
Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome . | Dyskerin
H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.[1][2][3]
This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.[3]
# Clinical significance
Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome .[4] | https://www.wikidoc.org/index.php/Dyskerin | |
1e666debea90e738a2ae472282721818a86aba29 | wikidoc | Dystonia | Dystonia
# Overview
Dystonia is a hyperkinetic movement disorder identified by involuntary sustained or intermittent contraction of a single or group of muscles that leads to repetitive movements or abnormal posture. The typical dystonic movements are usually rhythmic or patterned contractions that may be accompanied by tremor.
# Historical Perspective
- The term Dystonia was first introduced by Hermann Oppenheim, a German Neurologist , in 1911 following delineating abnormal posturing (dystonia muscularum deformans) in 4 unrelated Jewish children.
- The association between hereditary factors and dystonia was made in 1959 during reporting families with similar symptoms .
- The association between genes and dystonia was made in 1989 during introducing DYT1 or TOR1A gene as a major cause of young-onset generalized dystonia .
- In 1989, Ozelius .et.al were the first to discover the association between ITD1 gene ( further known as DYT1 gene ) and the development of dystonia.
- The variant "Focal Dystonia" was first introduced by Charles David Marsden, an English Neurologist, in 1976, following reporting different cases of adult-onset blepharospasm and/or oromandibular dystonia,, torticollis, spasmodic dysphonia, and writer’s cramp without any hereditary background or known cause.
# Classification
Dystonia may be classified into several subtypes based on age of onset, topographic distribution, temporal aspects, associated clinical features and etiology .
- Dystonia may be classified into five subtypes based on the age of onset; infancy (up to two years), childhood (3-12 years), adolescence (13-20 years), early adulthood (21-40 years) and late adulthood (>40 years)
- Dystonia may be classified into five subtypes based on the topographic distribution : focal, segmental, multifocal, generalized or hemidystonia
- Focal : if only one body part of the body is involved. The examples include writing dystonia, cervical dystonia, blepharospasm, Oromandibular dystonia and laryngeal or lingual dystonia
- Segmental : if two or more contiguous parts are involved. The examples include bi-brachial and cranial dystonia.
- Multifocal : if two or more noncontiguous parts are involved. The examples include dystonia of the right arm and the left leg
- Hemidystonia : if half of the body is involved.
- Dystonia is classified as generalized if trunk and two or more other parts are involved.
- Dystonia may be classified into eight subtypes based on the temporal aspects of the disease : manner of onset (acute versus insidious), symptoms variability (diurnal, intermittent, or action induced), and overall progression (static versus progressive).
- Dystonia may be classified into five subtypes based on associated clinical features:
- Dystonia is classified into four subtypes based on the etiology: Known Pathology of the nervous system, inherited, acquired or idiopathic
- Nervous system pathology : if there are any structural lesion or confirmed degeneration
- Inherited: if there is autosomal dominant, autosomal recessive , X-linked recessive or mitochondrial pattern of inheritance
- Acquired : if there is any history of brain injury, infection, toxic or drug consumption, vascular event, neoplasm or psychogenic cause
- Idiopathic
# Pathophysiology
Th exact pathogenesis of dystonia is not fully understood. However, the main mechanism has been attributed to the impaired central inhibitory circuits. It is thought that dystonia is the result of changes in synaptic pathways, reduced brain inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and decreased inhibition at the level of spinal, brain stem and especially cortex of the brain. It is also thought that dystonia may be associated with microscopic changes in brain stem nuclei, loss of Purkinje cells and axonal swelling in the cerebellum, changes in basal ganglia-cerebello-thalamo-cortical pathway and cerebellar and basal ganglia structures.
# Causes
Common known causes of dystonia include:
- Genetic mutations in TOR1A, THAP1, GCH1 and KMT2B
- Brain injury or infections including perinatal hopoxic injury, encephalitis, brain abscess or neoplasms, stroke and neurotoxic agents that affect basal ganglia (especially putamen), cerebellum, thalamus regions
- Diseases contributing to degenerative changes in central nervous system including Wilson's disease, GM1 and GM2 gangliosidosis, homocyctinuria, Lesch Nyhan syndrome and ataxia-telangiectasia
- Drugs including dopamin receptor blocking agents, amine depletors, serotonin-reuptake inhibitors, monoamine-oxidase inhibitors, calcium antagonists, benzodiazepines, general anesthetic agents, carbamazepine, phenytoin, triptans, ranitidine, cocaine or ecstasy
# Differential diagnosis
Dystonia must be differentiated from other diseases that cause neurological manifestations in infants.
# Treatment
Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief as does reducing stress, getting plenty of rest, moderate exercise and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side affects and risks.
Physicians may prescribe a series of different medications on a trial-and-error basis in an effort to find a combination that is effective for a specific patient. Not all patients will respond well to the same medications. Drugs that have had positive results in some patients include anti-Parkinsons agents (Trihexyphenidyl), muscle relaxers (Valium), keppra, and beta-blockers including "off-label" uses for some blood pressure medications.
Drugs, such as anticholinergics which act as an inhibitor of the neurotransmitter acetylcholine, may provide some relief. Clonazepam, an anti-seizure medicine, is also sometimes prescribed. However, for most sufferers their effects are limited and side affects like mental confusion, sedation, mood swings and short term memory loss occur.
Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3-6 months, depending on the kind of dystonia. Bo-Tox injections have the advantage of ready avalibility (the same form is used for cosmetic surgery) and the affects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups causing weakness or paralysis in them. The injections have to be repeated as the effects wear off and around 15% of recipients will develop immunity to the toxin. There is a Type A and Type B toxin approved for treatment of dystonia; often those that develop resistance to Type A may be able to use Type B.
Surgery, such as the denervation of selected muscles, may also provide some relief, however, the destruction of nerves in the limbs or brain is not reversable and should only be considered in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proved successful in a number of cases of severe generalised dystonia.
One type of dystonia, dopa-responsive dystonia can be completely treated with regular doses of L-dopa in a form such as Sinemet (carbidopa/levodopa). Although this doesn't remove the condition, it does alleviate the symptoms most of the time.
A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal chord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin.
Physical therapy can sometimes help with focal dystonia. A structured set of exercises are tailored to help the affected area. | Dystonia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: : Shadi Ghourchian, M.D.
# Overview
Dystonia is a hyperkinetic movement disorder identified by involuntary sustained or intermittent contraction of a single or group of muscles that leads to repetitive movements or abnormal posture.[1] The typical dystonic movements are usually rhythmic or patterned contractions that may be accompanied by tremor.[2][3]
# Historical Perspective
- The term Dystonia was first introduced by Hermann Oppenheim, a German Neurologist , in 1911 following delineating abnormal posturing (dystonia muscularum deformans) in 4 unrelated Jewish children.[4]
- The association between hereditary factors and dystonia was made in 1959 during reporting families with similar symptoms . [5]
- The association between genes and dystonia was made in 1989 during introducing DYT1 or TOR1A gene as a major cause of young-onset generalized dystonia .[6][7]
- In 1989, Ozelius .et.al were the first to discover the association between ITD1 gene ( further known as DYT1 gene ) and the development of dystonia. [7]
- The variant "Focal Dystonia" was first introduced by Charles David Marsden, an English Neurologist, in 1976, following reporting different cases of adult-onset blepharospasm and/or oromandibular dystonia,, torticollis, spasmodic dysphonia, and writer’s cramp without any hereditary background or known cause. [8]
# Classification
Dystonia may be classified into several subtypes based on age of onset, topographic distribution, temporal aspects, associated clinical features and etiology .[1][9][10]
- Dystonia may be classified into five subtypes based on the age of onset; infancy (up to two years), childhood (3-12 years), adolescence (13-20 years), early adulthood (21-40 years) and late adulthood (>40 years)
- Dystonia may be classified into five subtypes based on the topographic distribution : focal, segmental, multifocal, generalized or hemidystonia
- Focal : if only one body part of the body is involved. The examples include writing dystonia, cervical dystonia, blepharospasm, Oromandibular dystonia and laryngeal or lingual dystonia
- Segmental : if two or more contiguous parts are involved. The examples include bi-brachial and cranial dystonia.
- Multifocal : if two or more noncontiguous parts are involved. The examples include dystonia of the right arm and the left leg
- Hemidystonia : if half of the body is involved.
- Dystonia is classified as generalized if trunk and two or more other parts are involved.
- Dystonia may be classified into eight subtypes based on the temporal aspects of the disease : manner of onset (acute versus insidious), symptoms variability (diurnal, intermittent, or action induced), and overall progression (static versus progressive).
- Dystonia may be classified into five subtypes based on associated clinical features:
- Dystonia is classified into four subtypes based on the etiology: Known Pathology of the nervous system, inherited, acquired or idiopathic
- Nervous system pathology : if there are any structural lesion or confirmed degeneration
- Inherited: if there is autosomal dominant, autosomal recessive , X-linked recessive or mitochondrial pattern of inheritance
- Acquired : if there is any history of brain injury, infection, toxic or drug consumption, vascular event, neoplasm or psychogenic cause
- Idiopathic
# Pathophysiology
Th exact pathogenesis of dystonia is not fully understood. However, the main mechanism has been attributed to the impaired central inhibitory circuits. It is thought that dystonia is the result of changes in synaptic pathways, reduced brain inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and decreased inhibition at the level of spinal, brain stem and especially cortex of the brain. [11][12][13][14][15] It is also thought that dystonia may be associated with microscopic changes in brain stem nuclei, loss of Purkinje cells and axonal swelling in the cerebellum, changes in basal ganglia-cerebello-thalamo-cortical pathway and cerebellar and basal ganglia structures.[16][17][18][19][20][3]
# Causes
Common known causes of dystonia include:[10][21][22][19][23]
- Genetic mutations in TOR1A, THAP1, GCH1 and KMT2B
- Brain injury or infections including perinatal hopoxic injury, encephalitis, brain abscess or neoplasms, stroke and neurotoxic agents that affect basal ganglia (especially putamen), cerebellum, thalamus regions
- Diseases contributing to degenerative changes in central nervous system including Wilson's disease, GM1 and GM2 gangliosidosis, homocyctinuria, Lesch Nyhan syndrome and ataxia-telangiectasia
- Drugs including dopamin receptor blocking agents, amine depletors, serotonin-reuptake inhibitors, monoamine-oxidase inhibitors, calcium antagonists, benzodiazepines, general anesthetic agents, carbamazepine, phenytoin, triptans, ranitidine, cocaine or ecstasy
# Differential diagnosis
Dystonia must be differentiated from other diseases that cause neurological manifestations in infants.
# Treatment
Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief as does reducing stress, getting plenty of rest, moderate exercise and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side affects and risks.
Physicians may prescribe a series of different medications on a trial-and-error basis in an effort to find a combination that is effective for a specific patient. Not all patients will respond well to the same medications. Drugs that have had positive results in some patients include anti-Parkinsons agents (Trihexyphenidyl), muscle relaxers (Valium), keppra, and beta-blockers including "off-label" uses for some blood pressure medications.
Drugs, such as anticholinergics which act as an inhibitor of the neurotransmitter acetylcholine, may provide some relief. Clonazepam, an anti-seizure medicine, is also sometimes prescribed. However, for most sufferers their effects are limited and side affects like mental confusion, sedation, mood swings and short term memory loss occur.
Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3-6 months, depending on the kind of dystonia. Bo-Tox injections have the advantage of ready avalibility (the same form is used for cosmetic surgery) and the affects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups causing weakness or paralysis in them. The injections have to be repeated as the effects wear off and around 15% of recipients will develop immunity to the toxin. There is a Type A and Type B toxin approved for treatment of dystonia; often those that develop resistance to Type A may be able to use Type B.[24]
Surgery, such as the denervation of selected muscles, may also provide some relief, however, the destruction of nerves in the limbs or brain is not reversable and should only be considered in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proved successful in a number of cases of severe generalised dystonia.[25]
One type of dystonia, dopa-responsive dystonia can be completely treated with regular doses of L-dopa in a form such as Sinemet (carbidopa/levodopa). Although this doesn't remove the condition, it does alleviate the symptoms most of the time.
A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal chord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin.[26]
Physical therapy can sometimes help with focal dystonia. A structured set of exercises are tailored to help the affected area. | https://www.wikidoc.org/index.php/Dyskinesia | |
b1686eacf2a2631d915f0959720459ada6958a44 | wikidoc | Dysmelia | Dysmelia
Dysmelia (from Greek Δύσ - = "bad" plus μέλος (plural μέλεα) = "limb") is a congenital disorder referring to the limbs.
Dysmelia can refer to
- missing (aplasia) limbs: amelia, oligodactyly, congenital amputation
- malformation of limbs: ectrodactyly, phocomelia, syndactyly, brachydactyly, clubfoot
- too many limbs: polymelia, polydactyly, polysyndactyly
# Occurrence rate
Birth defects involving limbs occur in 1 per 1000.
# Causes
Dysmelia can be caused by
- inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)
- external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome
- teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals
- ionizing radiation (atomic weapons, radioiodine, radiation therapy)
- infections
- metabolic imbalance
de:dysmelie | Dysmelia
Dysmelia (from Greek Δύσ - = "bad" plus μέλος (plural μέλεα) = "limb") is a congenital disorder referring to the limbs.
Dysmelia can refer to
- missing (aplasia) limbs: amelia, oligodactyly, congenital amputation
- malformation of limbs: ectrodactyly, phocomelia, syndactyly, brachydactyly, clubfoot
- too many limbs: polymelia, polydactyly, polysyndactyly
# Occurrence rate
Birth defects involving limbs occur in 1 per 1000.
# Causes
Dysmelia can be caused by
- inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)
- external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome
- teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals
- ionizing radiation (atomic weapons, radioiodine, radiation therapy)
- infections
- metabolic imbalance
de:dysmelie
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Dysmelia | |
9bf65e59db737b358186e0fdb511e00f10059bb1 | wikidoc | Dystocia | Dystocia
# Overview
Dystocia (antonym eutocia) is an abnormal or difficult childbirth or labour. Dystocia may arise due to incoordinate uterine activity, abnormal fetal lie or presentation, or absolute or relative cephalopelvic disproportion. Oxytocin is commonly used to treat incoordinate uterine activity. However, pregnancies complicated by dystocia often end with assisted deliveries including forceps, ventouse or, commonly, caesarean section. Recognized risks of dystocia include fetal death, respiratory depression, hypoxic ischemic encephalopathy, and brachial nerve damage.
Shoulder dystocia is a specific case of dystocia whereby the anterior shoulder of the infant cannot pass below the pubic symphysis, or requires significant manipulation to pass below, the pubic symphysis.
A prolonged second stage of labour is another type oftocia whereby the fetus has not been delivered within three hours after the mother's cervix has become fully dilated.
Synonyms: difficult labour, abnormal labour, difficult childbirth, abnormal childbirth, dysfunctional labour
Dystocia pertaining to birds and reptiles is also called egg binding. See egg bound. | Dystocia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dystocia (antonym eutocia) is an abnormal or difficult childbirth or labour. Dystocia may arise due to incoordinate uterine activity, abnormal fetal lie or presentation, or absolute or relative cephalopelvic disproportion. Oxytocin is commonly used to treat incoordinate uterine activity. However, pregnancies complicated by dystocia often end with assisted deliveries including forceps, ventouse or, commonly, caesarean section. Recognized risks of dystocia include fetal death, respiratory depression, hypoxic ischemic encephalopathy, and brachial nerve damage.
Shoulder dystocia is a specific case of dystocia whereby the anterior shoulder of the infant cannot pass below the pubic symphysis, or requires significant manipulation to pass below, the pubic symphysis.
A prolonged second stage of labour is another type oftocia whereby the fetus has not been delivered within three hours after the mother's cervix has become fully dilated.
Synonyms: difficult labour, abnormal labour, difficult childbirth, abnormal childbirth, dysfunctional labour
Dystocia pertaining to birds and reptiles is also called egg binding. See egg bound.
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Dystocia | |
7543bcae0704c831f0071662440074f3aaeba4fc | wikidoc | Dystonin | Dystonin
Dystonin (DST), also known as Bullous pemphigoid antigen 1,(BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the DST gene.
This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been known that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.
# Interactions
Dystonin has been shown to interact with Collagen, type XVII, alpha 1, DCTN1 and Erbin. | Dystonin
Dystonin (DST), also known as Bullous pemphigoid antigen 1,(BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the DST gene.[1][2][3]
This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been known that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.[3]
# Interactions
Dystonin has been shown to interact with Collagen, type XVII, alpha 1,[4][5] DCTN1[6] and Erbin.[7] | https://www.wikidoc.org/index.php/Dystonin | |
e3085a869c31dacecd9c7db742adf8354a108164 | wikidoc | E number | E number
E numbers are number codes for food additives and are usually found on food labels throughout the European Union. The numbering scheme follows that of the International Numbering System (INS) as determined by the Codex Alimentarius committee. Only a subset of the INS additives are approved for use in the European Union, the 'E' prefix which stands for Europe. In casual language in the UK and Ireland, the term "E-number" is used as a pejorative term for artificial food additives, and products may promote themselves as "free of E-numbers" even though some of the ingredients (e.g. bicarbonate of soda) do have such a code.
E numbers are also encountered on food labeling in other jurisdictions, including the GCC, Australia, New Zealand and Israel. They are increasingly (though still rarely) found on North American packaging, especially in Canada.
# Classification by numeric range
NB: Not all examples of a class fall into the given numeric range. Moreover, many chemicals, particularly in the E400–499 range, have a variety of purposes.
# Full list
## E100–E199 (colours)
- E100 Curcumin, turmeric (food colouring)
- E101 Riboflavin (Vitamin B2), formerly called lactoflavin (Vitamin G) (food colouring)
- E101a Crushed Ants-like that of in smarties
- E102 Tartrazine (FD&C Yellow 5) (food colouring)
- E103 Chrysoine resorcinol (food colouring)
- E104 Quinoline yellow (food colouring)
- E105 Fast Yellow AB (food colouring)
- E106 Riboflavin-5-Sodium Phosphate (food colouring)
- E107 Yellow 2G (food colouring)
- E110 Sunset Yellow FCF, Orange Yellow S, FD&C Yellow 6 (food colouring)
- E111 Orange GGN (food colouring)
- E120 Cochineal, Carminic acid, Carmines, Natural Red 4 (food colouring)
- E121 Orcein, Orchil (food colouring)
- E122 Carmoisine, Azorubine (food colouring)
- E123 Amaranth (FD&C Red 2) (food colouring)
- E124 Ponceau 4R, Cochineal Red A, Brilliant Scarlet 4R (food colouring)
- E125 Ponceau SX, Scarlet GN (food colouring)
- E126 Ponceau 6R (food colouring)
- E127 Erythrosine (FD&C Red 3) (food colouring)
- E128 Red 2G (food colouring)
- E129 Allura Red AC (FD&C Red 40) (food colouring)
- E130 Indanthrene blue RS (food colouring)
- E131 Patent Blue V (food colouring)
- E132 Indigo carmine, Indigotine, FD&C Blue 2 (food colouring)
- E133 Brilliant Blue FCF (FD&C Blue 1) (food colouring)
- E140 Chlorophylls and Chlorophyllins: (i) Chlorophylls (ii) Chlorophyllins (food colouring)
- E141 Copper complexes of chlorophylls and chlorophyllins (i) Copper complexes of chlorophylls (ii) Copper complexes of chlorophyllins (food colouring)
- E142 Greens S (food colouring)
- E143 Fast Green FCF (FD&C Green 3) (food colouring)
- E150a Plain Caramel (food colouring)
- E150b Caustic sulfite caramel (food colouring)
- E150c Ammonia caramel (food colouring)
- E150d Sulphite ammonia caramel (food colouring)
- E151 Black PN, Brilliant Black BN (food colouring)
- E152 Black 7984 (food colouring)
- E153 Carbon black, Vegetable carbon (food colouring)
- E154 Brown FK, Kipper Brown (food colouring)
- E155 Brown HT, Chocolate brown HT (food colouring)
- E160a Alpha-carotene, Beta-carotene, Gamma-carotene (food colouring)
- E160b Annatto, bixin, norbixin (food colouring)
- E160c Paprika extract, Capsanthin, capsorubin (food colouring)
- E160d Lycopene (food colouring)
- E160e Beta-apo-8'-carotenal (C 30) (food colouring)
- E160f Ethyl ester of beta-apo-8'-carotenic acid (C 30) (food colouring)
- E161a Flavoxanthin (food colouring)
- E161b Lutein (food colouring)
- E161c Cryptoxanthin (food colouring)
- E161d Rubixanthin (food colouring)
- E161e Violaxanthin (food colouring)
- E161f Rhodoxanthin (food colouring)
- E161g Canthaxanthin (food colouring)
- E161h Zeaxanthin (food colouring)
- E161i Citranaxanthin (food colouring)
- E161j Astaxanthin (food colouring)
- E162 Beetroot Red, Betanin (food colouring)
- E163 Anthocyanins (food colouring)
- E170 Calcium carbonate, Chalk (food colouring)
- E171 Titanium dioxide (food colouring)
- E172 Iron oxides and hydroxides (food colouring)
- E173 Aluminium (food colouring)
- E174 Silver (food colouring)
- E175 Gold (food colouring)
- E180 Pigment Rubine, Lithol Rubine BK (food colouring)
- E181 Tannin (food colouring)
## E200–E299 (preservatives)
- E200 Sorbic acid (preservative)
- E201 Sodium sorbate (preservative)
- E202 Potassium sorbate (preservative)
- E203 Calcium sorbate (preservative)
- E210 Benzoic acid (preservative)
- E211 Sodium benzoate (preservative)
- E212 Potassium benzoate (preservative)
- E213 Calcium benzoate (preservative)
- E214 Ethylparaben (ethyl para-hydroxybenzoate) (preservative)
- E215 Sodium ethyl para-hydroxybenzoate (preservative)
- E216 Propylparaben (propyl para-hydroxybenzoate) (preservative)
- E217 Sodium propyl para-hydroxybenzoate (preservative)
- E218 Methylparaben (methyl para-hydroxybenzoate) (preservative)
- E219 Sodium methyl para-hydroxybenzoate (preservative)
- E220 Sulphur dioxide (preservative)
- E221 Sodium sulphite (preservative)
- E222 Sodium bisulphite (sodium hydrogen sulphite) (preservative)
- E223 Sodium metabisulphite (preservative)
- E224 Potassium metabisulphite (preservative)
- E225 Potassium sulphite (preservative)
- E226 Calcium sulphite (preservative)
- E227 Calcium hydrogen sulphite (preservative) (firming agent)
- E228 Potassium hydrogen sulphite (preservative)
- E230 Biphenyl, diphenyl (preservative)
- E231 Orthophenyl phenol (preservative)
- E232 Sodium orthophenyl phenol (preservative)
- E233 Thiabendazole (preservative)
- E234 Nisin (preservative)
- E235 Natamycin, Pimaracin (preservative)
- E236 Formic acid (preservative)
- E237 Sodium formate (preservative)
- E238 Calcium formate (preservative)
- E239 Hexamine (hexamethylene tetramine) (preservative)
- E240 Formaldehyde (preservative)
- E242 Dimethyl dicarbonate (preservative)
- E249 Potassium nitrite (preservative)
- E250 Sodium nitrite (preservative)
- E251 Sodium nitrate (preservative)
- E252 Potassium nitrate (Saltpetre) (preservative)
- E260 Acetic acid (preservative) (acidity regulator)
- E261 Potassium acetate (preservative) (acidity regulator)
- E262 Sodium acetates (i) Sodium acetate (ii) Sodium hydrogen acetate (sodium diacetate) (preservative) (acidity regulator)
- E263 Calcium acetate (preservative) (acidity regulator)
- E264 Ammonium acetate (preservative)
- E270 Lactic acid (preservative) (acid) (antioxidant)
- E280 Propionic acid (preservative)
- E281 Sodium propionate (preservative)
- E282 Calcium propionate (preservative)
- E283 Potassium propionate (preservative)
- E284 Boric acid (preservative)
- E285 Sodium tetraborate (borax) (preservative)
- E290 Carbon dioxide (acidity regulator)
- E296 Malic acid (acid) (acidity regulator)
- E297 Fumaric acid (acidity regulator)
## E300–E399 (antioxidants, acidity regulators)
- E300 Ascorbic acid (Vitamin C) (antioxidant)
- E301 Sodium ascorbate (antioxidant)
- E302 Calcium ascorbate (antioxidant)
- E303 Potassium ascorbate (antioxidant)
- E304 Fatty acid esters of ascorbic acid (i) Ascorbyl palmitate (ii) Ascorbyl stearate (antioxidant)
- E306 Tocopherol-rich extract (natural) (antioxidant)
- E307 Alpha-tocopherol (synthetic) (antioxidant)
- E308 Gamma-tocopherol (synthetic) (antioxidant)
- E309 Delta-tocopherol (synthetic) (antioxidant)
- E310 Propyl gallate (antioxidant)
- E311 Octyl gallate (antioxidant)
- E312 Dodecyl gallate (antioxidant)
- E315 Erythorbic acid (antioxidant)
- E316 Sodium erythorbate (antioxidant)
- E317 Erythorbin acid (antioxidant)
- E318 Sodium erythorbin (antioxidant)
- E319 tert-Butylhydroquinone (TBHQ) (antioxidant)
- E320 Butylated hydroxyanisole (BHA) (antioxidant)
- E321 Butylated hydroxytoluene (BHT) (antioxidant)
- E322 Lecithin (emulsifier)
- E325 Sodium lactate (antioxidant)
- E326 Potassium lactate (antioxidant) (acidity regulator)
- E327 Calcium lactate (antioxidant)
- E329 Magnesium lactate (antioxidant)
- E330 Citric acid (antioxidant) (acidity regulator)
- E331 Sodium citrates (i) Monosodium citrate (ii) Disodium citrate (iii) Sodium citrate (trisodium citrate) (antioxidant)
- E332 Potassium citrates (i) Monopotassium citrate (ii) Potassium citrate (tripotassium citrate) (antioxidant)
- E333 Calcium citrates (i) Monocalcium citrate (ii) Dicalcium citrate (iii) Calcium citrate (tricalcium citrate) (acidity regulator) (firming agent) (sequestrant)
- E334 Tartaric acid (L(+)-) (acid) (antioxidant)
- E335 Sodium tartrates (i) Monosodium tartrate (ii), Disodium tartrate (antioxidant)
- E336 Potassium tartrates (i) Monopotassium tartrate (cream of tartar) (ii) Dipotassium tartrate (antioxidant)
- E337 Sodium potassium tartrate (antioxidant)
- E338 Phosphoric acid (antioxidant)
- E339 Sodium phosphates (i) Monosodium phosphate (ii) Disodium phosphate (iii) Trisodium phosphate (antioxidant)
- E340 Potassium phosphates (i) Monopotassium phosphate (ii) Dipotassium phosphate (iii) Tripotassium phosphate (antioxidant)
- E341 Calcium phosphates (i) Monocalcium phosphate (ii) Dicalcium phosphate (iii) Tricalcium phosphate (anti-caking agent) (firming agent)
- E343 Magnesium phosphates (i) monomagnesium phosphate (ii) Dimagnesium phosphate (anti-caking agent) (Note - this additive is under discussion and may be included in a future amendment to the Directive on miscellaneous additives)
- E350 Sodium malates (i) Sodium malate (ii) Sodium hydrogen malate (acidity regulator)
- E351 Potassium malate (acidity regulator)
- E352 Calcium malates (i) Calcium malate (ii) Calcium hydrogen malate (acidity regulator)
- E353 Metatartaric acid (emulsifier)
- E354 Calcium tartrate (emulsifier)
- E355 Adipic acid (acidity regulator)
- E356 Sodium adipate (acidity regulator)
- E357 Potassium adipate (acidity regulator)
- E363 Succinic acid (acidity regulator)
- E365 Sodium fumarate (acidity regulator)
- E366 Potassium fumarate (acidity regulator)
- E367 Calcium fumarate (acidity regulator)
- E370 1,4-Heptonolactone (acidity regulator)
- E375 Niacin (nicotinic acid), Nicotinamide (colour retention agent)
- E380 Triammonium citrate (acidity regulator)
- E381 Ammoniumferrocitrate (acidity regulator)
- E385 Calcium disodium ethylene diamine tetra-acetate, (Calcium disodium EDTA) (sequestrant)
## E400–E499 (thickeners, stabilizers, emulsifiers)
- E400 Alginic acid (thickener) (stabiliser) (gelling agent) (emulsifier)
- E401 Sodium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E402 Potassium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E403 Ammonium alginate (thickener) (stabiliser) (emulsifier)
- E404 Calcium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E405 Propane-1,2-diol alginate (Propylene glycol alginate) (thickener) (stabiliser) (emulsifier)
- E406 Agar (thickener) (gelling agent) (stabiliser)
- E407 Carrageenan (thickener) (stabiliser) (gelling agent) (emulsifier)
- E407a Processed eucheuma seaweed (thickener) (stabiliser) (gelling agent) (emulsifier)
- E410 Locust bean gum (Carob gum) (thickener) (stabiliser) (gelling agent) (emulsifier)
- E412 Guar gum (thickener) (stabiliser)
- E413 Tragacanth (thickener) (stabiliser) (emulsifier)
- E414 Acacia gum (gum arabic) (thickener) (stabiliser) (emulsifier)
- E415 Xanthan gum (thickener) (stabiliser)
- E416 Karaya gum (thickener) (stabiliser) (emulsifier)
- E417 Tara gum (thickener) (stabiliser)
- E418 Gellan gum (thickener) (stabiliser) (emulsifier)
- E420 Sorbitol (i) Sorbitol (ii) Sorbitol syrup (emulsifier) (sweetener) (humectant)
- E421 Mannitol (anti-caking agent) (sweetener)
- E422 Glycerol (emulsifier) (sweetener)
- E425 Konjac (i) Konjac gum (ii) Konjac glucomannane (emulsifier)
- E430 Polyoxyethene (8) stearate (emulsifier) (stabiliser)
- E431 Polyoxyethene (40) stearate (emulsifier)
- E432 Polyoxyethene (20) sorbitan monolaurate (polysorbate 20) (emulsifier)
- E433 Polyoxyethene (20) sorbitan monooleate (polysorbate 80) (emulsifier)
- E434 Polyoxyethene (20) sorbitan monopalmitate (polysorbate 40) (emulsifier)
- E435 Polyoxyethene (20) sorbitan monostearate (polysorbate 60) (emulsifier)
- E436 Polyoxyethene (20) sorbitan tristearate (polysorbate 65) (emulsifier)
- E440 Pectins (i) pectin (ii) amidated pectin (emulsifier)
- E441 Gelatine (emulsifier) (gelling agent)
- E442 Ammonium phosphatides (emulsifier)
- E444 Sucrose acetate isobutyrate (emulsifier)
- E445 Glycerol esters of wood rosins (emulsifier)
- E450 Diphosphates (i) Disodium diphosphate (ii) Trisodium diphosphate (iii) Tetrasodium diphosphate (iv) Dipotassium diphosphate (v) Tetrapotassium diphosphate (vi) Dicalcium diphosphate (vii) Calcium dihydrogen diphosphate (emulsifier)
- E451 Triphosphates (i) Sodium tripolyphosphate (pentasodium triphosphate) (ii) Pentapotassium triphosphate (emulsifier)
- E452 Polyphosphates (i) Sodium polyphosphates (ii) Potassium polyphosphates (iii) Sodium calcium polyphosphate (iv) Calcium polyphophates (emulsifier)
- E459 Beta-cyclodextrine (emulsifier)
- E460 Cellulose (i) Microcrystalline cellulose (ii) Powdered cellulose (emulsifier)
- E461 Methyl cellulose (emulsifier)
- E462 Ethyl cellulose (emulsifier)
- E463 Hydroxypropyl cellulose (emulsifier)
- E464 Hydroxy propyl methyl cellulose (emulsifier)
- E465 Ethyl methyl cellulose (emulsifier)
- E466 Carboxymethyl cellulose, Sodium carboxy methyl cellulose (emulsifier)
- E468 Crosslinked sodium carboxymethyl cellulose (emulsifier) (Note - this additive is under discussion and may be included in a future amendment to the Directive on miscellaneous additives)
- E469 Enzymically hydrolysed carboxymethylcellulose (emulsifier)
- E470a Sodium, potassium and calcium salts of fatty acids (emulsifier) (anti-caking agent)
- E470b Magnesium salts of fatty acids (emulsifier) (anti-caking agent)
- E471 Mono- and diglycerides of fatty acids (glyceryl monostearate, glyceryl distearate) (emulsifier)
- E472a Acetic acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472b Lactic acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472c Citric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472d Tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472e Mono- and diacetyl tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472f Mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E473 Sucrose esters of fatty acids (emulsifier)
- E474 Sucroglycerides (emulsifier)
- E475 Polyglycerol esters of fatty acids (emulsifier)
- E476 Polyglycerol polyricinoleate (emulsifier)
- E477 Propane-1, 2-diol esters of fatty acids, propylene glycol esters of fatty acids (emulsifier)
- E478 Lactylated fatty acid esters of glycerol and propane-1 (emulsifier)
- E479b Thermally oxidized soya bean oil interacted with mono- and diglycerides of fatty acids (emulsifier)
- E481 Sodium stearoyl-2-lactylate (emulsifier)
- E482 Calcium stearoyl-2-lactylate (emulsifier)
- E483 Stearyl tartrate (emulsifier)
- E491 Sorbitan monostearate (emulsifier)
- E492 Sorbitan tristearate (emulsifier)
- E493 Sorbitan monolaurate (emulsifier)
- E494 Sorbitan monooleate (emulsifier)
- E495 Sorbitan monopalmitate (emulsifier)
## E500–E599 (acidity regulators, anti-caking agents)
- E500 Sodium carbonates (i) Sodium carbonate (ii) Sodium bicarbonate (Sodium hydrogen carbonate) (iii) Sodium sesquicarbonate (acidity regulator) (raising agent)
- E501 Potassium carbonates (i) Potassium carbonate (ii) Potassium bicarbonate (Potassium hydrogen carbonate) (acidity regulator)
- E503 Ammonium carbonates (i) Ammonium carbonate (ii) Ammonium bicarbonate (Ammonium hydrogen carbonate) (acidity regulator)
- E504 Magnesium carbonates (i) Magnesium carbonate (ii) Magnesium bicarbonate (Magnesium hydrogen carbonate) (acidity regulator) (anti-caking agent)
- E507 Hydrochloric acid (acid)
- E508 Potassium chloride (gelling agent) (seasoning)
- E509 Calcium chloride (sequestrant) (firming agent)
- E510 Ammonium chloride, ammonia solution (acidity regulator) (improving agent)
- E511 Magnesium chloride (firming agent)
- E512 Stannous chloride (antioxidant)
- E513 Sulphuric acid (acid)
- E517 Ammonium sulphate (improving agent)
- E518 Magnesium sulfate (Epsom salts), (acidity regulator) (firming agent)
- E519 Copper(II) sulphate (preservative)
- E520 Aluminium sulphate (firming agent)
- E521 Aluminium sodium sulphate (firming agent)
- E522 Aluminium potassium sulphate (acidity regulator)
- E523 Aluminium ammonium sulphate (acidity regulator)
- E524 Sodium hydroxide (acidity regulator)
- E525 Potassium hydroxide (acidity regulator)
- E526 Calcium hydroxide (acidity regulator) (firming agent)
- E527 Ammonium hydroxide (acidity regulator)
- E528 Magnesium hydroxide (acidity regulator)
- E529 Calcium oxide (acidity regulator) (improving agent)
- E530 Magnesium oxide (acidity regulator) (anti-caking agent)
- E535 Sodium ferrocyanide (acidity regulator) (anti-caking agent)
- E536 Potassium ferrocyanide (anti-caking agent)
- E538 Calcium ferrocyanide (anti-caking agent)
- E540 Dicalcium diphosphate (acidity regulator) (emulsifier)
- E541 Sodium aluminium phosphate, acidic (emulsifier)
- E542 Bone phosphate (anti-caking agent)
- E543 Calcium sodium polyphosphate
- E544 Calcium polyphosphate (emulsifier)
- E545 Ammonium polyphosphate (emulsifier)
- E550 Sodium silicate (anti-caking agent)
- E551 Silicon dioxide (Silica) (emulsifier) (anti-caking agent)
- E552 Calcium silicate (anti-caking agent)
- E553a (i) Magnesium silicate (ii) Magnesium trisilicate (anti-caking agent)
- E553b Talc (anti-caking agent)
- E554 Sodium aluminosilicate (sodium aluminium silicate) (anti-caking agent)
- E555 Potassium aluminium silicate (anti-caking agent)
- E556 Calcium aluminosilicate (calcium aluminium silicate) (anti-caking agent)
- E558 Bentonite (anti-caking agent)
- E559 Aluminium silicate (Kaolin) (anti-caking agent)
- E560 Potassium silicate (anti-caking agent)
- E570 Stearic acid (Fatty acid) (anti-caking agent)
- E572 Magnesium stearate, calcium stearate (emulsifier) (anti-caking agent)
- E574 Gluconic acid (acidity regulator)
- E575 Glucono-delta-lactone (acidity regulator) (sequestrant)
- E576 Sodium gluconate (sequestrant)
- E577 Potassium gluconate (sequestrant)
- E578 Calcium gluconate (firming agent)
- E579 Ferrous gluconate (food colouring)
- E585 Ferrous lactate (food colouring)
## E600–E699 (flavour enhancers)
- E620 Glutamic acid (flavour enhancer)
- E621 Monosodium glutamate (MSG) (flavour enhancer)
- E622 Monopotassium glutamate (flavour enhancer)
- E623 Calcium diglutamate (flavour enhancer)
- E624 Monoammonium glutamate (flavour enhancer)
- E625 Magnesium diglutamate (flavour enhancer)
- E626 Guanylic acid (flavour enhancer)
- E627 Disodium guanylate, sodium guanylate (flavour enhancer)
- E628 Dipotassium guanylate (flavour enhancer)
- E629 Calcium guanylate (flavour enhancer)
- E630 Inosinic acid (flavour enhancer)
- E631 Disodium inosinate (flavour enhancer)
- E632 Dipotassium inosinate (flavour enhancer)
- E633 Calcium inosinate (flavour enhancer)
- E634 Calcium 5'-ribonucleotides (flavour enhancer)
- E635 Disodium 5'-ribonucleotides (flavour enhancer)
- E636 Maltol (flavour enhancer)
- E637 Ethyl maltol (flavour enhancer)
- E640 Glycine and its sodium salt (flavour enhancer)
## E900–E999 (miscellaneous)
- E900 Dimethyl polysiloxane (anti-foaming agent) (anti-caking agent)
- E901 Beeswax , white and yellow (glazing agent)
- E902 Candelilla wax (glazing agent)
- E903 Carnauba wax (glazing agent)
- E904 Shellac (glazing agent)
- E905 Paraffins
- E905a Mineral oil (anti-foaming agent)
- E905b Petrolatum
- E905c Microcrystalline wax (glazing agent)
- E906 Gum benzoic (flavour enhancer)
- E907 Crystalline wax (glazing agent)
- E908 Rice bran wax (glazing agent)
- E910 L-cysteine
- E912 Montan wax
- E913 Lanolin, sheep wool grease (glazing agent)
- E914 Oxidized polyethylene wax (glazing agent)
- E915 Esters of colophony (glazing agent)
- E920 L-cysteine (improving agent)
- E921 L-cystine (improving agent)
- E922 Potassium persulfate (improving agent)
- E923 Ammonium persulfate (improving agent)
- E924 Potassium bromate (improving agent)
- E925 Chlorine (preservative) (bleach) (improving agent)
- E926 Chlorine dioxide (preservative) (bleach)
- E927 Azodicarbonamide (improving agent)
- E927b Carbamide (improving agent)
- E928 Benzoyl peroxide (improving agent) (bleach)
- E930 Calcium peroxide (improving agent) (bleach)
- E938 Argon (packaging gas)
- E939 Helium (packaging gas)
- E940 dichlorodifluoromethane (packaging gas) (rarely used)
- E941 Nitrogen (packaging gas) (propellant)
- E942 Nitrous oxide (propellant)
- E943a Butane (propellant)
- E943b Isobutane (propellant)
- E944 Propane (propellant)
- E948 Oxygen (packaging gas)
- E949 Hydrogen (packaging gas)
- E950 Acesulfame potassium (sweetener)
- E951 Aspartame (sweetener)
- E952 Cyclamic acid and its sodium and calcium salts, also known as Cyclamate (sweetener)
- E953 Isomalt (sweetener)
- E954 Saccharin and its sodium, potassium and calcium salts (sweetener)
- E955 Sucralose (sweetener)
- E956 Alitame (sweetener)
- E957 Thaumatin (sweetener) (flavour enhancer)
- E959 Neohesperidine dihydrochalcone (sweetener) (flavour enhancer)
- E962 Aspartame-acesulfame salt (sweetener) (stabiliser)
- E965 Maltitol (i) Maltitol (ii) Maltitol syrup (sweetener) (stabiliser) (humectant)
- E966 Lactitol (sweetener)
- E967 Xylitol (sweetener)
- E999 Quillaia extract (foaming agent)
## E1000–E1999 (additional chemicals)
- E1103 Invertase (stabiliser)
- E1105 Lysozyme (preservative)
- E1200 Polydextrose (stabiliser) (thickening agent) (humectant) (carrier)
- E1201 Polyvinylpyrrolidone (stabiliser)
- E1202 Polyvinylpolypyrrolidone (carrier) (stabiliser)
- E1400 Dextrin (stabiliser) (thickening agent)
- E1401 Modified starch (stabiliser) (thickening agent)
- E1402 Alkaline modified starch (stabiliser) (thickening agent)
- E1403 Bleached starch (stabiliser) (thickening agent)
- E1404 Oxidized starch (emulsifier) (thickening agent)
- E1410 Monostarch phosphate (stabiliser) (thickening agent)
- E1412 Distarch phosphate (stabiliser) (thickening agent)
- E1413 Phosphated distarch phosphate (stabiliser) (thickening agent)
- E1414 Acetylated distarch phosphate (emulsifier) (thickening agent)
- E1420 Acetylated starch, mono starch acetate (stabiliser) (thickening agent)
- E1421 Acetylated starch, mono starch acetate (stabiliser) (thickening agent)
- E1422 Acetylated distarch adipate (stabiliser) (thickening agent)
- E1430 Distarch glycerine (stabiliser) (thickening agent)
- E1440 Hydroxy propyl starch (emulsifier) (thickening agent)
- E1441 Hydroxy propyl distarch glycerine (stabiliser) (thickening agent)
- E1442 Hydroxy propyl distarch phosphate (stabiliser) (thickening agent)
- E1450 Starch sodium octenyl succinate (emulsifier) (stabiliser) (thickening agent)
- E1451 Acetylated oxidised starch (emulsifier) (thickening agent)
- E1501 Benzylated hydrocarbons
- E1502 Butane-1, 3-diol
- E1503 Castor Oil
- E1504 Ethyl Acetate
- E1505 Triethyl citrate (foam stabiliser)
- E1510 Ethanol
- E1517 Glyceryl diacetate or diacetin
- E1518 Glyceryl triacetate or triacetin (humectant)
- E1519 Benzyl alcohol
- E1520 Propylene glycol (humectant) | E number
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
E numbers are number codes for food additives and are usually found on food labels throughout the European Union. The numbering scheme follows that of the International Numbering System (INS) as determined by the Codex Alimentarius committee. Only a subset of the INS additives are approved for use in the European Union, the 'E' prefix which stands for Europe. In casual language in the UK and Ireland, the term "E-number" is used as a pejorative term for artificial food additives, and products may promote themselves as "free of E-numbers" even though some of the ingredients (e.g. bicarbonate of soda) do have such a code.
E numbers are also encountered on food labeling in other jurisdictions, including the GCC, Australia, New Zealand and Israel. They are increasingly (though still rarely) found on North American packaging, especially in Canada.
# Classification by numeric range
NB: Not all examples of a class fall into the given numeric range. Moreover, many chemicals, particularly in the E400–499 range, have a variety of purposes.
# Full list
## E100–E199 (colours)
- E100 Curcumin, turmeric (food colouring)
- E101 Riboflavin (Vitamin B2), formerly called lactoflavin (Vitamin G) (food colouring)
- E101a Crushed Ants-like that of in smarties
- E102 Tartrazine (FD&C Yellow 5) (food colouring)
- E103 Chrysoine resorcinol (food colouring)
- E104 Quinoline yellow (food colouring)
- E105 Fast Yellow AB (food colouring)
- E106 Riboflavin-5-Sodium Phosphate (food colouring)
- E107 Yellow 2G (food colouring)
- E110 Sunset Yellow FCF, Orange Yellow S, FD&C Yellow 6 (food colouring)
- E111 Orange GGN (food colouring)
- E120 Cochineal, Carminic acid, Carmines, Natural Red 4 (food colouring)
- E121 Orcein, Orchil (food colouring)
- E122 Carmoisine, Azorubine (food colouring)
- E123 Amaranth (FD&C Red 2) (food colouring)
- E124 Ponceau 4R, Cochineal Red A, Brilliant Scarlet 4R (food colouring)
- E125 Ponceau SX, Scarlet GN (food colouring)
- E126 Ponceau 6R (food colouring)
- E127 Erythrosine (FD&C Red 3) (food colouring)
- E128 Red 2G (food colouring)
- E129 Allura Red AC (FD&C Red 40) (food colouring)
- E130 Indanthrene blue RS (food colouring)
- E131 Patent Blue V (food colouring)
- E132 Indigo carmine, Indigotine, FD&C Blue 2 (food colouring)
- E133 Brilliant Blue FCF (FD&C Blue 1) (food colouring)
- E140 Chlorophylls and Chlorophyllins: (i) Chlorophylls (ii) Chlorophyllins (food colouring)
- E141 Copper complexes of chlorophylls and chlorophyllins (i) Copper complexes of chlorophylls (ii) Copper complexes of chlorophyllins (food colouring)
- E142 Greens S (food colouring)
- E143 Fast Green FCF (FD&C Green 3) (food colouring)
- E150a Plain Caramel (food colouring)
- E150b Caustic sulfite caramel (food colouring)
- E150c Ammonia caramel (food colouring)
- E150d Sulphite ammonia caramel (food colouring)
- E151 Black PN, Brilliant Black BN (food colouring)
- E152 Black 7984 (food colouring)
- E153 Carbon black, Vegetable carbon (food colouring)
- E154 Brown FK, Kipper Brown (food colouring)
- E155 Brown HT, Chocolate brown HT (food colouring)
- E160a Alpha-carotene, Beta-carotene, Gamma-carotene (food colouring)
- E160b Annatto, bixin, norbixin (food colouring)
- E160c Paprika extract, Capsanthin, capsorubin (food colouring)
- E160d Lycopene (food colouring)
- E160e Beta-apo-8'-carotenal (C 30) (food colouring)
- E160f Ethyl ester of beta-apo-8'-carotenic acid (C 30) (food colouring)
- E161a Flavoxanthin (food colouring)
- E161b Lutein (food colouring)
- E161c Cryptoxanthin (food colouring)
- E161d Rubixanthin (food colouring)
- E161e Violaxanthin (food colouring)
- E161f Rhodoxanthin (food colouring)
- E161g Canthaxanthin (food colouring)
- E161h Zeaxanthin (food colouring)
- E161i Citranaxanthin (food colouring)
- E161j Astaxanthin (food colouring)
- E162 Beetroot Red, Betanin (food colouring)
- E163 Anthocyanins (food colouring)
- E170 Calcium carbonate, Chalk (food colouring)
- E171 Titanium dioxide (food colouring)
- E172 Iron oxides and hydroxides (food colouring)
- E173 Aluminium (food colouring)
- E174 Silver (food colouring)
- E175 Gold (food colouring)
- E180 Pigment Rubine, Lithol Rubine BK (food colouring)
- E181 Tannin (food colouring)
## E200–E299 (preservatives)
- E200 Sorbic acid (preservative)
- E201 Sodium sorbate (preservative)
- E202 Potassium sorbate (preservative)
- E203 Calcium sorbate (preservative)
- E210 Benzoic acid (preservative)
- E211 Sodium benzoate (preservative)
- E212 Potassium benzoate (preservative)
- E213 Calcium benzoate (preservative)
- E214 Ethylparaben (ethyl para-hydroxybenzoate) (preservative)
- E215 Sodium ethyl para-hydroxybenzoate (preservative)
- E216 Propylparaben (propyl para-hydroxybenzoate) (preservative)
- E217 Sodium propyl para-hydroxybenzoate (preservative)
- E218 Methylparaben (methyl para-hydroxybenzoate) (preservative)
- E219 Sodium methyl para-hydroxybenzoate (preservative)
- E220 Sulphur dioxide (preservative)
- E221 Sodium sulphite (preservative)
- E222 Sodium bisulphite (sodium hydrogen sulphite) (preservative)
- E223 Sodium metabisulphite (preservative)
- E224 Potassium metabisulphite (preservative)
- E225 Potassium sulphite (preservative)
- E226 Calcium sulphite (preservative)
- E227 Calcium hydrogen sulphite (preservative) (firming agent)
- E228 Potassium hydrogen sulphite (preservative)
- E230 Biphenyl, diphenyl (preservative)
- E231 Orthophenyl phenol (preservative)
- E232 Sodium orthophenyl phenol (preservative)
- E233 Thiabendazole (preservative)
- E234 Nisin (preservative)
- E235 Natamycin, Pimaracin (preservative)
- E236 Formic acid (preservative)
- E237 Sodium formate (preservative)
- E238 Calcium formate (preservative)
- E239 Hexamine (hexamethylene tetramine) (preservative)
- E240 Formaldehyde (preservative)
- E242 Dimethyl dicarbonate (preservative)
- E249 Potassium nitrite (preservative)
- E250 Sodium nitrite (preservative)
- E251 Sodium nitrate (preservative)
- E252 Potassium nitrate (Saltpetre) (preservative)
- E260 Acetic acid (preservative) (acidity regulator)
- E261 Potassium acetate (preservative) (acidity regulator)
- E262 Sodium acetates (i) Sodium acetate (ii) Sodium hydrogen acetate (sodium diacetate) (preservative) (acidity regulator)
- E263 Calcium acetate (preservative) (acidity regulator)
- E264 Ammonium acetate (preservative)
- E270 Lactic acid (preservative) (acid) (antioxidant)
- E280 Propionic acid (preservative)
- E281 Sodium propionate (preservative)
- E282 Calcium propionate (preservative)
- E283 Potassium propionate (preservative)
- E284 Boric acid (preservative)
- E285 Sodium tetraborate (borax) (preservative)
- E290 Carbon dioxide (acidity regulator)
- E296 Malic acid (acid) (acidity regulator)
- E297 Fumaric acid (acidity regulator)
## E300–E399 (antioxidants, acidity regulators)
- E300 Ascorbic acid (Vitamin C) (antioxidant)
- E301 Sodium ascorbate (antioxidant)
- E302 Calcium ascorbate (antioxidant)
- E303 Potassium ascorbate (antioxidant)
- E304 Fatty acid esters of ascorbic acid (i) Ascorbyl palmitate (ii) Ascorbyl stearate (antioxidant)
- E306 Tocopherol-rich extract (natural) (antioxidant)
- E307 Alpha-tocopherol (synthetic) (antioxidant)
- E308 Gamma-tocopherol (synthetic) (antioxidant)
- E309 Delta-tocopherol (synthetic) (antioxidant)
- E310 Propyl gallate (antioxidant)
- E311 Octyl gallate (antioxidant)
- E312 Dodecyl gallate (antioxidant)
- E315 Erythorbic acid (antioxidant)
- E316 Sodium erythorbate (antioxidant)
- E317 Erythorbin acid (antioxidant)
- E318 Sodium erythorbin (antioxidant)
- E319 tert-Butylhydroquinone (TBHQ) (antioxidant)
- E320 Butylated hydroxyanisole (BHA) (antioxidant)
- E321 Butylated hydroxytoluene (BHT) (antioxidant)
- E322 Lecithin (emulsifier)
- E325 Sodium lactate (antioxidant)
- E326 Potassium lactate (antioxidant) (acidity regulator)
- E327 Calcium lactate (antioxidant)
- E329 Magnesium lactate (antioxidant)
- E330 Citric acid (antioxidant) (acidity regulator)
- E331 Sodium citrates (i) Monosodium citrate (ii) Disodium citrate (iii) Sodium citrate (trisodium citrate) (antioxidant)
- E332 Potassium citrates (i) Monopotassium citrate (ii) Potassium citrate (tripotassium citrate) (antioxidant)
- E333 Calcium citrates (i) Monocalcium citrate (ii) Dicalcium citrate (iii) Calcium citrate (tricalcium citrate) (acidity regulator) (firming agent) (sequestrant)
- E334 Tartaric acid (L(+)-) (acid) (antioxidant)
- E335 Sodium tartrates (i) Monosodium tartrate (ii), Disodium tartrate (antioxidant)
- E336 Potassium tartrates (i) Monopotassium tartrate (cream of tartar) (ii) Dipotassium tartrate (antioxidant)
- E337 Sodium potassium tartrate (antioxidant)
- E338 Phosphoric acid (antioxidant)
- E339 Sodium phosphates (i) Monosodium phosphate (ii) Disodium phosphate (iii) Trisodium phosphate (antioxidant)
- E340 Potassium phosphates (i) Monopotassium phosphate (ii) Dipotassium phosphate (iii) Tripotassium phosphate (antioxidant)
- E341 Calcium phosphates (i) Monocalcium phosphate (ii) Dicalcium phosphate (iii) Tricalcium phosphate (anti-caking agent) (firming agent)
- E343 Magnesium phosphates (i) monomagnesium phosphate (ii) Dimagnesium phosphate (anti-caking agent) (Note - this additive is under discussion and may be included in a future amendment to the Directive on miscellaneous additives)
- E350 Sodium malates (i) Sodium malate (ii) Sodium hydrogen malate (acidity regulator)
- E351 Potassium malate (acidity regulator)
- E352 Calcium malates (i) Calcium malate (ii) Calcium hydrogen malate (acidity regulator)
- E353 Metatartaric acid (emulsifier)
- E354 Calcium tartrate (emulsifier)
- E355 Adipic acid (acidity regulator)
- E356 Sodium adipate (acidity regulator)
- E357 Potassium adipate (acidity regulator)
- E363 Succinic acid (acidity regulator)
- E365 Sodium fumarate (acidity regulator)
- E366 Potassium fumarate (acidity regulator)
- E367 Calcium fumarate (acidity regulator)
- E370 1,4-Heptonolactone (acidity regulator)
- E375 Niacin (nicotinic acid), Nicotinamide (colour retention agent)
- E380 Triammonium citrate (acidity regulator)
- E381 Ammoniumferrocitrate (acidity regulator)
- E385 Calcium disodium ethylene diamine tetra-acetate, (Calcium disodium EDTA) (sequestrant)
## E400–E499 (thickeners, stabilizers, emulsifiers)
- E400 Alginic acid (thickener) (stabiliser) (gelling agent) (emulsifier)
- E401 Sodium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E402 Potassium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E403 Ammonium alginate (thickener) (stabiliser) (emulsifier)
- E404 Calcium alginate (thickener) (stabiliser) (gelling agent) (emulsifier)
- E405 Propane-1,2-diol alginate (Propylene glycol alginate) (thickener) (stabiliser) (emulsifier)
- E406 Agar (thickener) (gelling agent) (stabiliser)
- E407 Carrageenan (thickener) (stabiliser) (gelling agent) (emulsifier)
- E407a Processed eucheuma seaweed (thickener) (stabiliser) (gelling agent) (emulsifier)
- E410 Locust bean gum (Carob gum) (thickener) (stabiliser) (gelling agent) (emulsifier)
- E412 Guar gum (thickener) (stabiliser)
- E413 Tragacanth (thickener) (stabiliser) (emulsifier)
- E414 Acacia gum (gum arabic) (thickener) (stabiliser) (emulsifier)
- E415 Xanthan gum (thickener) (stabiliser)
- E416 Karaya gum (thickener) (stabiliser) (emulsifier)
- E417 Tara gum (thickener) (stabiliser)
- E418 Gellan gum (thickener) (stabiliser) (emulsifier)
- E420 Sorbitol (i) Sorbitol (ii) Sorbitol syrup (emulsifier) (sweetener) (humectant)
- E421 Mannitol (anti-caking agent) (sweetener)
- E422 Glycerol (emulsifier) (sweetener)
- E425 Konjac (i) Konjac gum (ii) Konjac glucomannane (emulsifier)
- E430 Polyoxyethene (8) stearate (emulsifier) (stabiliser)
- E431 Polyoxyethene (40) stearate (emulsifier)
- E432 Polyoxyethene (20) sorbitan monolaurate (polysorbate 20) (emulsifier)
- E433 Polyoxyethene (20) sorbitan monooleate (polysorbate 80) (emulsifier)
- E434 Polyoxyethene (20) sorbitan monopalmitate (polysorbate 40) (emulsifier)
- E435 Polyoxyethene (20) sorbitan monostearate (polysorbate 60) (emulsifier)
- E436 Polyoxyethene (20) sorbitan tristearate (polysorbate 65) (emulsifier)
- E440 Pectins (i) pectin (ii) amidated pectin (emulsifier)
- E441 Gelatine (emulsifier) (gelling agent)
- E442 Ammonium phosphatides (emulsifier)
- E444 Sucrose acetate isobutyrate (emulsifier)
- E445 Glycerol esters of wood rosins (emulsifier)
- E450 Diphosphates (i) Disodium diphosphate (ii) Trisodium diphosphate (iii) Tetrasodium diphosphate (iv) Dipotassium diphosphate (v) Tetrapotassium diphosphate (vi) Dicalcium diphosphate (vii) Calcium dihydrogen diphosphate (emulsifier)
- E451 Triphosphates (i) Sodium tripolyphosphate (pentasodium triphosphate) (ii) Pentapotassium triphosphate (emulsifier)
- E452 Polyphosphates (i) Sodium polyphosphates (ii) Potassium polyphosphates (iii) Sodium calcium polyphosphate (iv) Calcium polyphophates (emulsifier)
- E459 Beta-cyclodextrine (emulsifier)
- E460 Cellulose (i) Microcrystalline cellulose (ii) Powdered cellulose (emulsifier)
- E461 Methyl cellulose (emulsifier)
- E462 Ethyl cellulose (emulsifier)
- E463 Hydroxypropyl cellulose (emulsifier)
- E464 Hydroxy propyl methyl cellulose (emulsifier)
- E465 Ethyl methyl cellulose (emulsifier)
- E466 Carboxymethyl cellulose, Sodium carboxy methyl cellulose (emulsifier)
- E468 Crosslinked sodium carboxymethyl cellulose (emulsifier) (Note - this additive is under discussion and may be included in a future amendment to the Directive on miscellaneous additives)
- E469 Enzymically hydrolysed carboxymethylcellulose (emulsifier)
- E470a Sodium, potassium and calcium salts of fatty acids (emulsifier) (anti-caking agent)
- E470b Magnesium salts of fatty acids (emulsifier) (anti-caking agent)
- E471 Mono- and diglycerides of fatty acids (glyceryl monostearate, glyceryl distearate) (emulsifier)
- E472a Acetic acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472b Lactic acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472c Citric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472d Tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472e Mono- and diacetyl tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E472f Mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids (emulsifier)
- E473 Sucrose esters of fatty acids (emulsifier)
- E474 Sucroglycerides (emulsifier)
- E475 Polyglycerol esters of fatty acids (emulsifier)
- E476 Polyglycerol polyricinoleate (emulsifier)
- E477 Propane-1, 2-diol esters of fatty acids, propylene glycol esters of fatty acids (emulsifier)
- E478 Lactylated fatty acid esters of glycerol and propane-1 (emulsifier)
- E479b Thermally oxidized soya bean oil interacted with mono- and diglycerides of fatty acids (emulsifier)
- E481 Sodium stearoyl-2-lactylate (emulsifier)
- E482 Calcium stearoyl-2-lactylate (emulsifier)
- E483 Stearyl tartrate (emulsifier)
- E491 Sorbitan monostearate (emulsifier)
- E492 Sorbitan tristearate (emulsifier)
- E493 Sorbitan monolaurate (emulsifier)
- E494 Sorbitan monooleate (emulsifier)
- E495 Sorbitan monopalmitate (emulsifier)
## E500–E599 (acidity regulators, anti-caking agents)
- E500 Sodium carbonates (i) Sodium carbonate (ii) Sodium bicarbonate (Sodium hydrogen carbonate) (iii) Sodium sesquicarbonate (acidity regulator) (raising agent)
- E501 Potassium carbonates (i) Potassium carbonate (ii) Potassium bicarbonate (Potassium hydrogen carbonate) (acidity regulator)
- E503 Ammonium carbonates (i) Ammonium carbonate (ii) Ammonium bicarbonate (Ammonium hydrogen carbonate) (acidity regulator)
- E504 Magnesium carbonates (i) Magnesium carbonate (ii) Magnesium bicarbonate (Magnesium hydrogen carbonate) (acidity regulator) (anti-caking agent)
- E507 Hydrochloric acid (acid)
- E508 Potassium chloride (gelling agent) (seasoning)
- E509 Calcium chloride (sequestrant) (firming agent)
- E510 Ammonium chloride, ammonia solution (acidity regulator) (improving agent)
- E511 Magnesium chloride (firming agent)
- E512 Stannous chloride (antioxidant)
- E513 Sulphuric acid (acid)
- E517 Ammonium sulphate (improving agent)
- E518 Magnesium sulfate (Epsom salts), (acidity regulator) (firming agent)
- E519 Copper(II) sulphate (preservative)
- E520 Aluminium sulphate (firming agent)
- E521 Aluminium sodium sulphate (firming agent)
- E522 Aluminium potassium sulphate (acidity regulator)
- E523 Aluminium ammonium sulphate (acidity regulator)
- E524 Sodium hydroxide (acidity regulator)
- E525 Potassium hydroxide (acidity regulator)
- E526 Calcium hydroxide (acidity regulator) (firming agent)
- E527 Ammonium hydroxide (acidity regulator)
- E528 Magnesium hydroxide (acidity regulator)
- E529 Calcium oxide (acidity regulator) (improving agent)
- E530 Magnesium oxide (acidity regulator) (anti-caking agent)
- E535 Sodium ferrocyanide (acidity regulator) (anti-caking agent)
- E536 Potassium ferrocyanide (anti-caking agent)
- E538 Calcium ferrocyanide (anti-caking agent)
- E540 Dicalcium diphosphate (acidity regulator) (emulsifier)
- E541 Sodium aluminium phosphate, acidic (emulsifier)
- E542 Bone phosphate (anti-caking agent)
- E543 Calcium sodium polyphosphate
- E544 Calcium polyphosphate (emulsifier)
- E545 Ammonium polyphosphate (emulsifier)
- E550 Sodium silicate (anti-caking agent)
- E551 Silicon dioxide (Silica) (emulsifier) (anti-caking agent)
- E552 Calcium silicate (anti-caking agent)
- E553a (i) Magnesium silicate (ii) Magnesium trisilicate (anti-caking agent)
- E553b Talc (anti-caking agent)
- E554 Sodium aluminosilicate (sodium aluminium silicate) (anti-caking agent)
- E555 Potassium aluminium silicate (anti-caking agent)
- E556 Calcium aluminosilicate (calcium aluminium silicate) (anti-caking agent)
- E558 Bentonite (anti-caking agent)
- E559 Aluminium silicate (Kaolin) (anti-caking agent)
- E560 Potassium silicate (anti-caking agent)
- E570 Stearic acid (Fatty acid) (anti-caking agent)
- E572 Magnesium stearate, calcium stearate (emulsifier) (anti-caking agent)
- E574 Gluconic acid (acidity regulator)
- E575 Glucono-delta-lactone (acidity regulator) (sequestrant)
- E576 Sodium gluconate (sequestrant)
- E577 Potassium gluconate (sequestrant)
- E578 Calcium gluconate (firming agent)
- E579 Ferrous gluconate (food colouring)
- E585 Ferrous lactate (food colouring)
## E600–E699 (flavour enhancers)
- E620 Glutamic acid (flavour enhancer)
- E621 Monosodium glutamate (MSG) (flavour enhancer)
- E622 Monopotassium glutamate (flavour enhancer)
- E623 Calcium diglutamate (flavour enhancer)
- E624 Monoammonium glutamate (flavour enhancer)
- E625 Magnesium diglutamate (flavour enhancer)
- E626 Guanylic acid (flavour enhancer)
- E627 Disodium guanylate, sodium guanylate (flavour enhancer)
- E628 Dipotassium guanylate (flavour enhancer)
- E629 Calcium guanylate (flavour enhancer)
- E630 Inosinic acid (flavour enhancer)
- E631 Disodium inosinate (flavour enhancer)
- E632 Dipotassium inosinate (flavour enhancer)
- E633 Calcium inosinate (flavour enhancer)
- E634 Calcium 5'-ribonucleotides (flavour enhancer)
- E635 Disodium 5'-ribonucleotides (flavour enhancer)
- E636 Maltol (flavour enhancer)
- E637 Ethyl maltol (flavour enhancer)
- E640 Glycine and its sodium salt (flavour enhancer)
## E900–E999 (miscellaneous)
- E900 Dimethyl polysiloxane (anti-foaming agent) (anti-caking agent)
- E901 Beeswax , white and yellow (glazing agent)
- E902 Candelilla wax (glazing agent)
- E903 Carnauba wax (glazing agent)
- E904 Shellac (glazing agent)
- E905 Paraffins
- E905a Mineral oil (anti-foaming agent)
- E905b Petrolatum
- E905c Microcrystalline wax (glazing agent)
- E906 Gum benzoic (flavour enhancer)
- E907 Crystalline wax (glazing agent)
- E908 Rice bran wax (glazing agent)
- E910 L-cysteine
- E912 Montan wax
- E913 Lanolin, sheep wool grease (glazing agent)
- E914 Oxidized polyethylene wax (glazing agent)
- E915 Esters of colophony (glazing agent)
- E920 L-cysteine (improving agent)
- E921 L-cystine (improving agent)
- E922 Potassium persulfate (improving agent)
- E923 Ammonium persulfate (improving agent)
- E924 Potassium bromate (improving agent)
- E925 Chlorine (preservative) (bleach) (improving agent)
- E926 Chlorine dioxide (preservative) (bleach)
- E927 Azodicarbonamide (improving agent)
- E927b Carbamide (improving agent)
- E928 Benzoyl peroxide (improving agent) (bleach)
- E930 Calcium peroxide (improving agent) (bleach)
- E938 Argon (packaging gas)
- E939 Helium (packaging gas)
- E940 dichlorodifluoromethane (packaging gas) (rarely used)
- E941 Nitrogen (packaging gas) (propellant)
- E942 Nitrous oxide (propellant)
- E943a Butane (propellant)
- E943b Isobutane (propellant)
- E944 Propane (propellant)
- E948 Oxygen (packaging gas)
- E949 Hydrogen (packaging gas)
- E950 Acesulfame potassium (sweetener)
- E951 Aspartame (sweetener)
- E952 Cyclamic acid and its sodium and calcium salts, also known as Cyclamate (sweetener)
- E953 Isomalt (sweetener)
- E954 Saccharin and its sodium, potassium and calcium salts (sweetener)
- E955 Sucralose (sweetener)
- E956 Alitame (sweetener)
- E957 Thaumatin (sweetener) (flavour enhancer)
- E959 Neohesperidine dihydrochalcone (sweetener) (flavour enhancer)
- E962 Aspartame-acesulfame salt (sweetener) (stabiliser)
- E965 Maltitol (i) Maltitol (ii) Maltitol syrup (sweetener) (stabiliser) (humectant)
- E966 Lactitol (sweetener)
- E967 Xylitol (sweetener)
- E999 Quillaia extract (foaming agent)
## E1000–E1999 (additional chemicals)
- E1103 Invertase (stabiliser)
- E1105 Lysozyme (preservative)
- E1200 Polydextrose (stabiliser) (thickening agent) (humectant) (carrier)
- E1201 Polyvinylpyrrolidone (stabiliser)
- E1202 Polyvinylpolypyrrolidone (carrier) (stabiliser)
- E1400 Dextrin (stabiliser) (thickening agent)
- E1401 Modified starch (stabiliser) (thickening agent)
- E1402 Alkaline modified starch (stabiliser) (thickening agent)
- E1403 Bleached starch (stabiliser) (thickening agent)
- E1404 Oxidized starch (emulsifier) (thickening agent)
- E1410 Monostarch phosphate (stabiliser) (thickening agent)
- E1412 Distarch phosphate (stabiliser) (thickening agent)
- E1413 Phosphated distarch phosphate (stabiliser) (thickening agent)
- E1414 Acetylated distarch phosphate (emulsifier) (thickening agent)
- E1420 Acetylated starch, mono starch acetate (stabiliser) (thickening agent)
- E1421 Acetylated starch, mono starch acetate (stabiliser) (thickening agent)
- E1422 Acetylated distarch adipate (stabiliser) (thickening agent)
- E1430 Distarch glycerine (stabiliser) (thickening agent)
- E1440 Hydroxy propyl starch (emulsifier) (thickening agent)
- E1441 Hydroxy propyl distarch glycerine (stabiliser) (thickening agent)
- E1442 Hydroxy propyl distarch phosphate (stabiliser) (thickening agent)
- E1450 Starch sodium octenyl succinate (emulsifier) (stabiliser) (thickening agent)
- E1451 Acetylated oxidised starch (emulsifier) (thickening agent)
- E1501 Benzylated hydrocarbons
- E1502 Butane-1, 3-diol
- E1503 Castor Oil
- E1504 Ethyl Acetate
- E1505 Triethyl citrate (foam stabiliser)
- E1510 Ethanol
- E1517 Glyceryl diacetate or diacetin
- E1518 Glyceryl triacetate or triacetin (humectant)
- E1519 Benzyl alcohol
- E1520 Propylene glycol (humectant)
# External links
- E-codes and ingredients search engine with details/suggestions for Muslims
- Current EU approved additives and their E Numbers
- E Number Index
- Food Additives in the European Union
- List of Food Additives, database for mobile phones
Template:E number infobox 900-909
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eo:E-numero
gl:Números E
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nl:E-nummer
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Template:WS | https://www.wikidoc.org/index.php/E_number | |
65dd8a90a7a0de62f15730f1c89504457e083238 | wikidoc | Egophony | Egophony
Synonyms and Keywords: e to a changes
# Overview
Egophony (British: Aegophony) is an increased resonance of voice sounds heard when auscultating the lungs, often caused by consolidated or compressed lung tissue due to an infection, pleural effusion, tumor, or congestion. It is due to enhanced transmission of high-frequency noise across fluid, such as in abnormal lung tissue, with lower frequencies filtered out. It results in a high-pitched nasal or bleating quality in the affected person's voice.
While listening to the lungs with a stethoscope, the patient is asked to say the letter "e." What is heard is a higher pitched sound that sounds like the letter "a." (Some doctors refer to this as "e to a changes.") Most commonly, this indicates pneumonia.
Similar terms are bronchophony and whispered pectoriloquy. The mechanism is the same: fluid or consolidation causes the sound of the voice to be transmitted loudly to the periphery of the lungs where it is usually not heard.
Egophony comes from the Greek word for "goat," (aix, aig-) in reference to the bleating quality of the sound. | Egophony
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and Keywords: e to a changes
# Overview
Egophony (British: Aegophony) is an increased resonance of voice sounds heard when auscultating the lungs, often caused by consolidated or compressed lung tissue due to an infection, pleural effusion, tumor, or congestion. It is due to enhanced transmission of high-frequency noise across fluid, such as in abnormal lung tissue, with lower frequencies filtered out. It results in a high-pitched nasal or bleating quality in the affected person's voice.
While listening to the lungs with a stethoscope, the patient is asked to say the letter "e." What is heard is a higher pitched sound that sounds like the letter "a." (Some doctors refer to this as "e to a changes.") Most commonly, this indicates pneumonia.
Similar terms are bronchophony and whispered pectoriloquy. The mechanism is the same: fluid or consolidation causes the sound of the voice to be transmitted loudly to the periphery of the lungs where it is usually not heard.
Egophony comes from the Greek word for "goat," (aix, aig-) in reference to the bleating quality of the sound. [1] | https://www.wikidoc.org/index.php/E_to_a_changes | |
67bdc62541d4a2872b445e368454f114b645d916 | wikidoc | Ear drop | Ear drop
Ear drops are a form of medicine used to treat or prevent ear infections, especially infections of the outer ear and ear canal (Otitis externa).
Bacterial infections are sometimes treated with antibiotics. Examples are:-
- Gentisone HC ear drops (containing Gentamicin and hydrocortisone).
- Ciproxin HC ear drops (containing ciprofloxacin and hydrocortisone).
- Sofradex ear drops (containing Framycetin Sulphate, Gramicidin, Dexamethasone]]/
- Kenacomb ear drops, containing triamcinolone acetonide, neomycin and gramicidin (antibiotics) and nystatin (antifungal).
Over the counter ear drops are also available, including spirit drops (alcohol solution), which dries out the ear, and drops such as Aqua Ear (used for swimmer's ear) containing a mixture of substances such as alcohol and acetic acid, to dry the ear and make it difficult for microbes to grow.
# Cautions
If there is a possibility that you already have an ear infection, or your ear drum has ever been perforated, or otherwise injured, or if you have ever had ear surgery, it is important to consult an ear doctor (ENT, or ear, nose and throat specialist) before you use any type of ear drops (or before swimming). | Ear drop
Ear drops are a form of medicine used to treat or prevent ear infections, especially infections of the outer ear and ear canal (Otitis externa).
Bacterial infections are sometimes treated with antibiotics. Examples are:-
- Gentisone HC ear drops (containing Gentamicin and hydrocortisone).
- Ciproxin HC ear drops (containing ciprofloxacin and hydrocortisone).
- Sofradex ear drops (containing Framycetin Sulphate, Gramicidin, Dexamethasone]]/[[sodium metasulphobenzoate, Phenylethanol.[1]
- Kenacomb ear drops, containing triamcinolone acetonide, neomycin and gramicidin (antibiotics) and nystatin (antifungal).
Over the counter ear drops are also available, including spirit drops (alcohol solution), which dries out the ear, and drops such as Aqua Ear (used for swimmer's ear) containing a mixture of substances such as alcohol and acetic acid, to dry the ear and make it difficult for microbes to grow.[citation needed]
# Cautions
If there is a possibility that you already have an ear infection, or your ear drum has ever been perforated, or otherwise injured, or if you have ever had ear surgery, it is important to consult an ear doctor (ENT, or ear, nose and throat specialist) before you use any type of ear drops (or before swimming).[2] | https://www.wikidoc.org/index.php/Ear_drop |
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