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a08481eb4ada6661813eb27d1eb8538cda5c2e7c | wikidoc | Mebicar | Mebicar
# Overview
Mebicar (mebicarum) is an anxiolytic medication produced by Latvian pharmaceutical company Olainfarm and sold in the Russian Federation under the brand name Adaptol. It is not approved for use in the United States or European Union.
Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.
Mebicar purportedly has anti-anxiety (anxiolytic) properties.
It is also used to aid smoking cessation. In addition Mebicar may be useful in the treatment of ADHD symptoms. In contrast with typical anxiolytic medication like benzodiazepines Mebicar is non-habit forming, non-sedating and does not impair motor function. | Mebicar
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Mebicar (mebicarum) is an anxiolytic medication produced by Latvian pharmaceutical company Olainfarm and sold in the Russian Federation under the brand name Adaptol.[1] It is not approved for use in the United States or European Union.
Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.[2]
Mebicar purportedly has anti-anxiety (anxiolytic) properties.[2][3][4][5][6]
It is also used to aid smoking cessation.[1] In addition Mebicar may be useful in the treatment of ADHD symptoms.[7] In contrast with typical anxiolytic medication like benzodiazepines Mebicar is non-habit forming, non-sedating and does not impair motor function.[3][1] | https://www.wikidoc.org/index.php/Mebicar | |
c8865ddbd8011584d3ab74f5013e0c6771bb7e0a | wikidoc | Therapy | Therapy
# Overview
Therapy (in Greek: θεραπεία) is the attempted remediation of a health problem, usually following a diagnosis. In the medical field, it is synonomous with the word "treatment".
A supportive therapy is one that does not treat or improve the underlying condition, but instead increases the patient's comfort. Supportive treatment may be palliative care.
# Therapeutic effects
A therapeutic effect is a consequence of a medical treatment, of any kind, the results of which are judged to be desirable and beneficial. This is true whether the result was expected, unexpected, or even an unintended consequence of the treatment.
What constitutes a therapeutic effect vs. a side effect is a matter of both the nature of the situation in which a treatment is used and the goals of treatment.
# Adverse effects
In addition to (or in place of) the intended therapeutic effect of a treatment, a therapy may cause undesired (adverse) effects as well. When an adverse effect is weaker than the therapeutic effect, it is commonly referred to as a "side effect". An adverse effect may result from an unsuitable or incorrect dosage or procedure (which could be due to medical error). Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Patients sometimes quit a therapy because of its adverse effects. The severity of adverse effects ranges from nausea to death.
Common adverse effects include alteration in body weight, change in enzyme levels, loss of function, or pathological change detected at the microscopic, macroscopic or physiological level.
Adverse effects may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures (e.g. drug interaction). | Therapy
# Overview
Therapy (in Greek: θεραπεία) is the attempted remediation of a health problem, usually following a diagnosis. In the medical field, it is synonomous with the word "treatment".
A supportive therapy is one that does not treat or improve the underlying condition, but instead increases the patient's comfort.[1] Supportive treatment may be palliative care.
# Therapeutic effects
A therapeutic effect is a consequence of a medical treatment, of any kind, the results of which are judged to be desirable and beneficial. This is true whether the result was expected, unexpected, or even an unintended consequence of the treatment.
What constitutes a therapeutic effect vs. a side effect is a matter of both the nature of the situation in which a treatment is used and the goals of treatment.
# Adverse effects
In addition to (or in place of) the intended therapeutic effect of a treatment, a therapy may cause undesired (adverse) effects as well. When an adverse effect is weaker than the therapeutic effect, it is commonly referred to as a "side effect". An adverse effect may result from an unsuitable or incorrect dosage or procedure (which could be due to medical error). Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Patients sometimes quit a therapy because of its adverse effects. The severity of adverse effects ranges from nausea to death.
Common adverse effects include alteration in body weight, change in enzyme levels, loss of function, or pathological change detected at the microscopic, macroscopic or physiological level.
Adverse effects may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures (e.g. drug interaction). | https://www.wikidoc.org/index.php/Medical_treatment | |
77274dcd10eb5a9163b056433600f949b3dd0d0e | wikidoc | Medipix | Medipix
Medipix is a family of photon counting pixel detector developed by an international collaboration, hosted by CERN.
Detectors in the Medipix family include:
- Medipix 1
- Medipix 2
- Medipix MXR
- Timepix
- Medipix 3 (currently at the prototype development phase)
# Design
The detectors are hybrid detectors. This means that a sensor material, typically silicon, is bonded on to an electronics layer. The sensor layer is a semiconductor in which the incident radiation makes and electron/hole pair. The charge is then collected, via bump bonds, and processed by a CMOS electronics layer. The electronics count the number of events in each pixel. Discriminators are used so that the electronics only count events within a selected energy range.
Medipix-2, Timepix, and Medipix-3 are all 256x256 pixels, each 0.055mm square.
Timepix allows for recording time information regarding when events occur relative to when the shutter opens. In addition Time over Threshold (ToT) mode allows for recording the duration an event is above a threshold.
Medipix-3 has better energy resolution through real time correction of charge sharing. It also has multiple counters per pixel that can be used in several different modes. This allows for continuous readout and up to eight energy thresholds.
# Applications
- Astronomy
- High Energy Physics
- Medical Imaging
# History
- Medipix-1: Early 90s.
- Medipix-2: Late 90s.
- Medipix-3: Collaboration formed 2006. | Medipix
Medipix is a family of photon counting pixel detector developed by an international collaboration, hosted by CERN.
Detectors in the Medipix family include:
- Medipix 1
- Medipix 2
- Medipix MXR
- Timepix
- Medipix 3 (currently at the prototype development phase)
# Design
The detectors are hybrid detectors. This means that a sensor material, typically silicon, is bonded on to an electronics layer. The sensor layer is a semiconductor in which the incident radiation makes and electron/hole pair. The charge is then collected, via bump bonds, and processed by a CMOS electronics layer. The electronics count the number of events in each pixel. Discriminators are used so that the electronics only count events within a selected energy range.
Medipix-2, Timepix, and Medipix-3 are all 256x256 pixels, each 0.055mm square.
Timepix allows for recording time information regarding when events occur relative to when the shutter opens. In addition Time over Threshold (ToT) mode allows for recording the duration an event is above a threshold.
Medipix-3 has better energy resolution through real time correction of charge sharing. It also has multiple counters per pixel that can be used in several different modes. This allows for continuous readout and up to eight energy thresholds.
# Applications
- Astronomy
- High Energy Physics
- Medical Imaging
# History
- Medipix-1: Early 90s.
- Medipix-2: Late 90s.
- Medipix-3: Collaboration formed 2006.
# External links
- Medipix collaboration home page.
- Medipix-3 collaborators.
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Medipix | |
1ceef9bca7eb36945aa6b2b015b0d3b0a27d807f | wikidoc | Meiosis | Meiosis
In biology or life science, meiosis (pronounced my-oh-sis) is a process of reductional division in which the number of chromosomes per cell is cut in half. In animals, meiosis always results in the formation of gametes, while in other organisms it can give rise to spores.
Meiosis is essential for sexual reproduction and therefore occurs in all eukaryotes (including single-celled organisms) that reproduce sexually. A few eukaryotes, notably the Bdelloid rotifers, have lost the ability to carry out meiosis and have acquired the ability to reproduce by parthenogenesis. Meiosis does not occur in archaea or bacteria, which reproduce via asexual processes such as binary fission.
During meiosis, the genome of a diploid germ cell, which is composed of long segments of DNA packaged into chromosomes, undergoes DNA replication followed by two rounds of division, resulting in four haploid cells. Each of these cells contain one complete set of chromosomes, or half of the genetic content of the original cell. If meiosis produces gametes, these cells must fuse during fertilization to create a new diploid cell, or zygote before any new growth can occur. Thus, the division mechanism of meiosis is a reciprocal process to the joining of two genomes that occurs at fertilization. Because the chromosomes of each parent undergo genetic recombination during meiosis, each gamete, and thus each zygote, will have a unique genetic blueprint encoded in its DNA. Together, meiosis and fertilization constitute sexuality in the eukaryotes, and generate genetically distinct individuals in populations.
In all plants, and in many protists, meiosis results in the formation of haploid cells that can divide vegetatively without undergoing fertilization, referred to as spores. In these groups, gametes are produced by mitosis.
Meiosis uses many of the same biochemical mechanisms employed during mitosis to accomplish the redistribution of chromosomes. There are several features unique to meiosis, most importantly the pairing and genetic recombination between homologous chromosomes.
Meiosis comes from the root -meio, meaning less.
# History
Meiosis was discovered and described for the first time in sea urchin eggs in 1876, by noted German biologist Oscar Hertwig (1849-1922). It was described again in 1883, at the level of chromosomes, by Belgian zoologist Edouard Van Beneden (1846-1910), in Ascaris worms' eggs. The significance of meiosis for reproduction and inheritance, however, was described only in 1890 by German biologist August Weismann (1834-1914), who noted that two cell divisions were necessary to transform one diploid cell into four haploid cells if the number of chromosomes had to be maintained. In 1911 the American geneticist Thomas Hunt Morgan (1866-1945) observed crossover in Drosophila melanogaster meiosis and provided the first genetic evidence that genes are transmitted on chromosomes.
# Evolution
Meiosis is thought to have appeared 1.4 billion years ago. The only supergroup of eukaryotes which does not have meiosis in all organisms is excavata. The other five major supergroups, opisthokonts, amoebozoa, rhizaria, archaeplastida and chromalveolates all seem to have genes for meiosis universally present, even if not always functional. Some excavata species do have meiosis which is consistent with the hypothesis that this group is an ancient, paraphyletic grade. An example of eukaryotic organism in which meiosis does not exist is euglenoid.
# Occurrence of meiosis in eukaryotic life cycles
Meiosis occur in eukaryotic life cycles involving sexual reproduction, comprising of the constant cyclical process of meiosis and fertilization. This takes place alongside normal mitotic cell division. In multicellular organisms, there is an intermediary step between the diploid and haploid transition where the organism grows. The organism will then produce the germ cells that continue in the life cycle. The rest of the cells, called somatic cells, function within the organism and will die with it.
Cycling meiosis and fertilization events produces a series of transitions back and forth between alternating haploid and diploid states. The organism phase of the life cycle can occur either during the diploid state (gametic or diploid life cycle), during the haploid state (zygotic or haploid life cycle), or both (sporic or haplodiploid life cycle, in which there two distinct organism phases, one during the haploid state and the other during the diploid state). In this sense, there are three types of life cycles that utilize sexual reproduction, differentiated by the location of the organisms phase(s).
In the gametic life cycle, of which humans are a part, the species is diploid, grown from a diploid cell called the zygote. The organism's diploid germ-line stem cells undergo meiosis to create haploid gametes (the spermatozoa for males and ova for females), which fertilize to form the zygote. The diploid zygote undergoes repeated cellular division by mitosis to grow into the organism. Mitosis is a related process to meiosis that creates two cells that are genetically identical to the parent cell. The general principle is that mitosis creates somatic cells and meiosis creates germ cells.
In the zygotic life cycle the species is haploid instead, spawned by the proliferation and differentiation of a single haploid cell called the gamete. Two organisms of opposing gender contribute their haploid germ cells to form a diploid zygote. The zygote undergoes meiosis immediately, creating four haploid cells. These cells undergo mitosis to create the organism. Many fungi and many protozoa are members of the zygotic life cycle.
Finally, in the sporic life cycle, the living organism alternates between haploid and diploid states. Consequently, this cycle is also known as the alternation of generations. The diploid organism's germ-line cells undergo meiosis to produce gametes. The gametes proliferate by mitosis, growing into a haploid organism. The haploid organism's germ cells then combine with another haploid organism's cells, creating the zygote. The zygote undergoes repeated mitosis and differentiation to become the diploid organism again. The sporic life cycle can be considered a fusion of the gametic and zygotic life cycles.
# Process
Because meiosis is a "one-way" process, it cannot be said to engage in a cell cycle as mitosis does. However, the preparatory steps that lead up to meiosis are identical in pattern and name to the interphase of the mitotic cell cycle.
Interphase is divided into three phases:
- Gap 1 (G1) phase: This is a very active period, where the cell synthesizes its vast array of proteins, including the enzymes and structural proteins it will need for growth. In G1 stage each of the chromosomes consists of a single (very long) molecule of DNA. In humans, at this point cells are 46 chromosomes, 2N, identical to somatic cells.
- Synthesis (S) phase: The genetic material is replicated: each of its chromosomes duplicates, producing 46 chromosomes each made up of two sister chromatids. The cell is still considered diploid because it still contains the same number of centromeres. The identical sister chromatids have not yet condensed into the densely packaged chromosomes visible with the light microscope. This will take place during prophase I in meiosis.
- Gap 2 (G2) phase: G2 phase is absent in Meiosis
Interphase is followed by meiosis I and then meiosis II. Meiosis I consists of separating the pairs of homologous chromosome, each made up of two sister chromatids, into two cells. One entire haploid content of chromosomes is contained in each of the resulting daughter cells; the first meiotic division therefore reduces the ploidy of the original cell by a factor of 2.
Meiosis II consists of decoupling each chromosome's sister strands (chromatids), and segregating the individual chromatids into haploid daughter cells. The two cells resulting from meiosis I divide during meiosis II, creating 4 haploid daughter cells. Meiosis I and II are each divided into prophase, metaphase, anaphase, and telophase stages, similar in purpose to their analogous subphases in the mitotic cell cycle. Therefore, meiosis includes the stages of meiosis I (prophase I, metaphase I, anaphase I, telophase I), and meiosis II (prophase II, metaphase II, anaphase II, telophase II).
Meiosis generates genetic diversity in two ways: (1) independent alignment and subsequent separation of homologous chromosome pairs during the first meiotic division allows a random and independent selection of each chromosome segregates into each gamete; and (2) physical exchange of homologous chromosomal regions by recombination during prophase I results in new genetic combinations within chromosomes.
# Meiosis-phases
## Meiosis I
In meiosis I, the homologous pairs in a diploid cell separate, producing two haploid cells (23 chromosomes, N in humans), so meiosis I is referred to as a reductional division. A regular diploid human cell contains 46 chromosomes and is considered 2N because it contains 23 pairs of homologous chromosomes. However, after meiosis I, although the cell contains 46 chromosomes it is only considered N because later in anaphase I the sister chromatids will remain together as the spindle pulls the pair toward the pole of the new cell. In meiosis II, an equational division similar to mitosis will occur whereby the sister chromatids are finally split, creating a total of 4 haploid cells (23 chromosomes, N) per daughter cell from the first division.
### Prophase I
Homologous chromosomes pair (or synapse) and crossing over (or recombination) occurs - a step unique to meiosis. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatids, with one chromosome coming from each parent. At this stage, non-sister chromatids may cross-over at points called chiasmata (plural; singular chiasma).
The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads". During this stage, individual chromosomes begin to condense into long strands within the nucleus. However the two sister chromatids are still so tightly bound that they are indistinguishable from one another. The chromosomes in the leptotene stage show a specific arrangement where the telomeres are oriented towards the nuclear membrane. Hence, this stage is called "bouquet stage".
The zygotene stage, also known as zygonema, from Greek words meaning "paired threads", occurs as the chromosomes approximately line up with each other into homologous chromosomes.
The pachytene stage, also known as pachynema, from Greek words meaning "thick threads", contains the following chromosomal crossover. Nonsister chromatids of homologous chromosomes randomly exchange segments of genetic information over regions of homology. (Sex chromosomes, however, are not wholly identical, and only exchange information over a small region of homology.) Exchange takes place at sites where recombination nodules (the aforementioned chiasmata) have formed. The exchange of information between the non-sister chromatids results in a recombination of information; each chromosome has the complete set of information it had before, and there are no gaps formed as a result of the process. Because the chromosomes cannot be distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable through the microscope.
During the diplotene stage, also known as diplonema, from Greek words meaning "two threads", the synaptonemal complex degrades and homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions where crossing-over occurred. The chiasmata remain on the chromosomes until they are severed in Anaphase I.
In human fetal oogenesis all developing oocytes develop to this stage and stop before birth. This suspended state is referred to as the dictyotene stage and remains so until puberty. In males, only spermatogonia exist until meiosis begins at puberty.
Chromosomes condense further during the diakinesis stage, from Greek words meaning "moving through". This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindle begins to form.
During these stages, two centrosomes, containing a pair of centrioles in animal cells, migrate to the two poles of the cell. These centrosomes, which were duplicated during S-phase, function as microtubule organizing centers nucleating microtubules, which are essentially cellular ropes and poles. The microtubules invade the nuclear region after the nuclear envelope disintegrates, attaching to the chromosomes at the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centriole, like a train on a track. There are four kinetochores on each tetrad, but the pair of kinetochores on each sister chromatid fuses and functions as a unit during meiosis I.
Microtubules that attach to the kinetochores are known as kinetochore microtubules. Other microtubules will interact with microtubules from the opposite centriole: these are called nonkinetochore microtubules or polar microtubules. A third type of microtubules, the aster microtubules, radiates from the centrosome into the cytoplasm or contacts components of the membrane skeleton.
### Metaphase I
Homologous pairs move together along the metaphase plate:
As kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent along the metaphase plate, with respect to the orientation of the other bivalents along the same equatorial line.
### Anaphase I
Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous chromosomes apart. Since each chromosome has only one functional unit of a pair of kinetochores, whole chromosomes are pulled toward opposing poles, forming two haploid sets. Each chromosome still contains a pair of sister chromatids. Nonkinetochore microtubules lengthen, pushing the centrioles farther apart. The cell elongates in preparation for division down the center.
### Telophase I
The last meiotic division effectively ends when the chromosomes arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells. Sister chromatids remain attached during telophase I.
Cells may enter a period of rest known as interkinesis or interphase II. No DNA replication occurs during this stage.
## Meiosis II
Meiosis II is the second part of the meiotic process. Much of the process is similar to mitosis. The end result is production of four haploid cells (23 chromosomes, 1N in humans) from the two haploid cells (23 chromosomes, 1N - each of the chromosomes consisting of two sister chromatids) produced in meiosis I.
Prophase II takes an inversely proportional time compared to telophase I. In this prophase we see the disappearance of the nucleoli and the nuclear envelope again as well as the shortening and thickening of the chromatids. Centrioles move to the polar regions and arrange spindle fibers for the second meiotic division.
In metaphase II, the centromeres contain two kinetochores, that attach to spindle fibers from the centrosomes (centrioles) at each pole. The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plate.
This is followed by anaphase II, where the centromeres are cleaved, allowing microtubules attached to the kinetochores to pull the sister chromatids apart. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles.
The process ends with telophase II, which is similar to telophase I, and is marked by uncoiling and lengthening of the chromosomes and the disappearance of the spindle. Nuclear envelopes reform and cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes. Meiosis is now complete.
# The Significance of Meiosis
Meiosis facilitates stable sexual reproduction. Without the halving of ploidy, or chromosome count, fertilization would result in zygotes that have twice the number of chromosomes as the zygotes from the previous generation. Successive generations would have an exponential increase in chromosome count. In organisms that are normally diploid, polyploidy, the state of having three or more sets of chromosomes, results in developmental abnormalities or lethality . Polyploidy is poorly tolerated in most animal species. Plants, however, regularly produce fertile, viable polyploids. Polyploidy has been implicated as an important mechanism in plant speciation.
Most importantly, recombination and independent assortment of homologous chromosomes allow for a greater diversity of genotypes in the population. This produces genetic variation in gametes that promote genetic and phenotypic variation in a population of offspring.
# Nondisjunction
The normal separation of chromosomes in meiosis I or sister chromatids in meiosis II is termed disjunction. When the separation is not normal, it is called nondisjunction. This results in the production of gametes which have either too many of too few of a particular chromosome, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis.
This is a cause of several medical conditions in humans (such as):
- Down Syndrome - trisomy of chromosome 21
- Patau Syndrome - trisomy of chromosome 13
- Edward Syndrome - trisomy of chromosome 18
- Klinefelter Syndrome - extra X chromosomes in males - ie XXY, XXXY, XXXXY
- Turner Syndrome - lacking of one X chromosome in females - ie XO
- Triple X syndrome - and extra X chromosome in females
- XYY Syndrome - an extra Y chromosome in males
# Meiosis in humans
In females, meiosis occurs in cells known as oogonia (singular: oogonium). Each oogonium that initiates meiosis will divide twice to form a single oocyte and three polar bodies. However, before these divisions occur, these cells stop at the diplotene stage of meiosis I and lay dormant within a protective shell of somatic cells called the follicle. Follicles begin growth at a steady pace in a process known as folliculogenesis, and a small number enter the menstrual cycle. Menstruated oocytes continue meiosis I and arrest at meiosis II until fertilization. The process of meiosis in females occurs during oogenesis, and differs from the typical meiosis in that it features a long period of meiotic arrest known as the Dictyate stage and lacks the assistance of centrosomes.
In males, meiosis occurs in precursor cells known as spermatogonia that divide twice to become sperm. These cells continuously divide without arrest in the seminiferous tubules of the testicles. Sperm is produced at a steady pace. The process of meiosis in males occurs during spermatogenesis. | Meiosis
In biology or life science, meiosis (pronounced my-oh-sis) is a process of reductional division in which the number of chromosomes per cell is cut in half. In animals, meiosis always results in the formation of gametes, while in other organisms it can give rise to spores.
Meiosis is essential for sexual reproduction and therefore occurs in all eukaryotes (including single-celled organisms) that reproduce sexually. A few eukaryotes, notably the Bdelloid rotifers, have lost the ability to carry out meiosis and have acquired the ability to reproduce by parthenogenesis. Meiosis does not occur in archaea or bacteria, which reproduce via asexual processes such as binary fission.
During meiosis, the genome of a diploid germ cell, which is composed of long segments of DNA packaged into chromosomes, undergoes DNA replication followed by two rounds of division, resulting in four haploid cells. Each of these cells contain one complete set of chromosomes, or half of the genetic content of the original cell. If meiosis produces gametes, these cells must fuse during fertilization to create a new diploid cell, or zygote before any new growth can occur. Thus, the division mechanism of meiosis is a reciprocal process to the joining of two genomes that occurs at fertilization. Because the chromosomes of each parent undergo genetic recombination during meiosis, each gamete, and thus each zygote, will have a unique genetic blueprint encoded in its DNA. Together, meiosis and fertilization constitute sexuality in the eukaryotes, and generate genetically distinct individuals in populations.
In all plants, and in many protists, meiosis results in the formation of haploid cells that can divide vegetatively without undergoing fertilization, referred to as spores. In these groups, gametes are produced by mitosis.
Meiosis uses many of the same biochemical mechanisms employed during mitosis to accomplish the redistribution of chromosomes. There are several features unique to meiosis, most importantly the pairing and genetic recombination between homologous chromosomes.
Meiosis comes from the root -meio, meaning less.
# History
Meiosis was discovered and described for the first time in sea urchin eggs in 1876, by noted German biologist Oscar Hertwig (1849-1922). It was described again in 1883, at the level of chromosomes, by Belgian zoologist Edouard Van Beneden (1846-1910), in Ascaris worms' eggs. The significance of meiosis for reproduction and inheritance, however, was described only in 1890 by German biologist August Weismann (1834-1914), who noted that two cell divisions were necessary to transform one diploid cell into four haploid cells if the number of chromosomes had to be maintained. In 1911 the American geneticist Thomas Hunt Morgan (1866-1945) observed crossover in Drosophila melanogaster meiosis and provided the first genetic evidence that genes are transmitted on chromosomes.
# Evolution
Meiosis is thought to have appeared 1.4 billion years ago. The only supergroup of eukaryotes which does not have meiosis in all organisms is excavata. The other five major supergroups, opisthokonts, amoebozoa, rhizaria, archaeplastida and chromalveolates all seem to have genes for meiosis universally present, even if not always functional. Some excavata species do have meiosis which is consistent with the hypothesis that this group is an ancient, paraphyletic grade. An example of eukaryotic organism in which meiosis does not exist is euglenoid.
# Occurrence of meiosis in eukaryotic life cycles
Meiosis occur in eukaryotic life cycles involving sexual reproduction, comprising of the constant cyclical process of meiosis and fertilization. This takes place alongside normal mitotic cell division. In multicellular organisms, there is an intermediary step between the diploid and haploid transition where the organism grows. The organism will then produce the germ cells that continue in the life cycle. The rest of the cells, called somatic cells, function within the organism and will die with it.
Cycling meiosis and fertilization events produces a series of transitions back and forth between alternating haploid and diploid states. The organism phase of the life cycle can occur either during the diploid state (gametic or diploid life cycle), during the haploid state (zygotic or haploid life cycle), or both (sporic or haplodiploid life cycle, in which there two distinct organism phases, one during the haploid state and the other during the diploid state). In this sense, there are three types of life cycles that utilize sexual reproduction, differentiated by the location of the organisms phase(s).
In the gametic life cycle, of which humans are a part, the species is diploid, grown from a diploid cell called the zygote. The organism's diploid germ-line stem cells undergo meiosis to create haploid gametes (the spermatozoa for males and ova for females), which fertilize to form the zygote. The diploid zygote undergoes repeated cellular division by mitosis to grow into the organism. Mitosis is a related process to meiosis that creates two cells that are genetically identical to the parent cell. The general principle is that mitosis creates somatic cells and meiosis creates germ cells.
In the zygotic life cycle the species is haploid instead, spawned by the proliferation and differentiation of a single haploid cell called the gamete. Two organisms of opposing gender contribute their haploid germ cells to form a diploid zygote. The zygote undergoes meiosis immediately, creating four haploid cells. These cells undergo mitosis to create the organism. Many fungi and many protozoa are members of the zygotic life cycle.
Finally, in the sporic life cycle, the living organism alternates between haploid and diploid states. Consequently, this cycle is also known as the alternation of generations. The diploid organism's germ-line cells undergo meiosis to produce gametes. The gametes proliferate by mitosis, growing into a haploid organism. The haploid organism's germ cells then combine with another haploid organism's cells, creating the zygote. The zygote undergoes repeated mitosis and differentiation to become the diploid organism again. The sporic life cycle can be considered a fusion of the gametic and zygotic life cycles.
# Process
Because meiosis is a "one-way" process, it cannot be said to engage in a cell cycle as mitosis does. However, the preparatory steps that lead up to meiosis are identical in pattern and name to the interphase of the mitotic cell cycle.
Interphase is divided into three phases:
- Gap 1 (G1) phase: This is a very active period, where the cell synthesizes its vast array of proteins, including the enzymes and structural proteins it will need for growth. In G1 stage each of the chromosomes consists of a single (very long) molecule of DNA. In humans, at this point cells are 46 chromosomes, 2N, identical to somatic cells.
- Synthesis (S) phase: The genetic material is replicated: each of its chromosomes duplicates, producing 46 chromosomes each made up of two sister chromatids. The cell is still considered diploid because it still contains the same number of centromeres. The identical sister chromatids have not yet condensed into the densely packaged chromosomes visible with the light microscope. This will take place during prophase I in meiosis.
- Gap 2 (G2) phase: G2 phase is absent in Meiosis
Interphase is followed by meiosis I and then meiosis II. Meiosis I consists of separating the pairs of homologous chromosome, each made up of two sister chromatids, into two cells. One entire haploid content of chromosomes is contained in each of the resulting daughter cells; the first meiotic division therefore reduces the ploidy of the original cell by a factor of 2.
Meiosis II consists of decoupling each chromosome's sister strands (chromatids), and segregating the individual chromatids into haploid daughter cells. The two cells resulting from meiosis I divide during meiosis II, creating 4 haploid daughter cells. Meiosis I and II are each divided into prophase, metaphase, anaphase, and telophase stages, similar in purpose to their analogous subphases in the mitotic cell cycle. Therefore, meiosis includes the stages of meiosis I (prophase I, metaphase I, anaphase I, telophase I), and meiosis II (prophase II, metaphase II, anaphase II, telophase II).
Meiosis generates genetic diversity in two ways: (1) independent alignment and subsequent separation of homologous chromosome pairs during the first meiotic division allows a random and independent selection of each chromosome segregates into each gamete; and (2) physical exchange of homologous chromosomal regions by recombination during prophase I results in new genetic combinations within chromosomes.
# Meiosis-phases
## Meiosis I
In meiosis I, the homologous pairs in a diploid cell separate, producing two haploid cells (23 chromosomes, N in humans), so meiosis I is referred to as a reductional division. A regular diploid human cell contains 46 chromosomes and is considered 2N because it contains 23 pairs of homologous chromosomes. However, after meiosis I, although the cell contains 46 chromosomes it is only considered N because later in anaphase I the sister chromatids will remain together as the spindle pulls the pair toward the pole of the new cell. In meiosis II, an equational division similar to mitosis will occur whereby the sister chromatids are finally split, creating a total of 4 haploid cells (23 chromosomes, N) per daughter cell from the first division.
### Prophase I
Homologous chromosomes pair (or synapse) and crossing over (or recombination) occurs - a step unique to meiosis. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatids, with one chromosome coming from each parent. At this stage, non-sister chromatids may cross-over at points called chiasmata (plural; singular chiasma).
The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads".[1] During this stage, individual chromosomes begin to condense into long strands within the nucleus. However the two sister chromatids are still so tightly bound that they are indistinguishable from one another. The chromosomes in the leptotene stage show a specific arrangement where the telomeres are oriented towards the nuclear membrane. Hence, this stage is called "bouquet stage".
The zygotene stage, also known as zygonema, from Greek words meaning "paired threads",[1] occurs as the chromosomes approximately line up with each other into homologous chromosomes.
The pachytene stage, also known as pachynema, from Greek words meaning "thick threads",[1] contains the following chromosomal crossover. Nonsister chromatids of homologous chromosomes randomly exchange segments of genetic information over regions of homology. (Sex chromosomes, however, are not wholly identical, and only exchange information over a small region of homology.) Exchange takes place at sites where recombination nodules (the aforementioned chiasmata) have formed. The exchange of information between the non-sister chromatids results in a recombination of information; each chromosome has the complete set of information it had before, and there are no gaps formed as a result of the process. Because the chromosomes cannot be distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable through the microscope.
During the diplotene stage, also known as diplonema, from Greek words meaning "two threads",[1] the synaptonemal complex degrades and homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions where crossing-over occurred. The chiasmata remain on the chromosomes until they are severed in Anaphase I.
In human fetal oogenesis all developing oocytes develop to this stage and stop before birth. This suspended state is referred to as the dictyotene stage and remains so until puberty. In males, only spermatogonia exist until meiosis begins at puberty.
Chromosomes condense further during the diakinesis stage, from Greek words meaning "moving through".[1] This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindle begins to form.
During these stages, two centrosomes, containing a pair of centrioles in animal cells, migrate to the two poles of the cell. These centrosomes, which were duplicated during S-phase, function as microtubule organizing centers nucleating microtubules, which are essentially cellular ropes and poles. The microtubules invade the nuclear region after the nuclear envelope disintegrates, attaching to the chromosomes at the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centriole, like a train on a track. There are four kinetochores on each tetrad, but the pair of kinetochores on each sister chromatid fuses and functions as a unit during meiosis I. [2][3]
Microtubules that attach to the kinetochores are known as kinetochore microtubules. Other microtubules will interact with microtubules from the opposite centriole: these are called nonkinetochore microtubules or polar microtubules. A third type of microtubules, the aster microtubules, radiates from the centrosome into the cytoplasm or contacts components of the membrane skeleton.
### Metaphase I
Homologous pairs move together along the metaphase plate:
As kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent along the metaphase plate, with respect to the orientation of the other bivalents along the same equatorial line.
### Anaphase I
Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous chromosomes apart. Since each chromosome has only one functional unit of a pair of kinetochores[3], whole chromosomes are pulled toward opposing poles, forming two haploid sets. Each chromosome still contains a pair of sister chromatids. Nonkinetochore microtubules lengthen, pushing the centrioles farther apart. The cell elongates in preparation for division down the center.
### Telophase I
The last meiotic division effectively ends when the chromosomes arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells. Sister chromatids remain attached during telophase I.
Cells may enter a period of rest known as interkinesis or interphase II. No DNA replication occurs during this stage.
## Meiosis II
Meiosis II is the second part of the meiotic process. Much of the process is similar to mitosis. The end result is production of four haploid cells (23 chromosomes, 1N in humans) from the two haploid cells (23 chromosomes, 1N * each of the chromosomes consisting of two sister chromatids) produced in meiosis I.
Prophase II takes an inversely proportional time compared to telophase I. In this prophase we see the disappearance of the nucleoli and the nuclear envelope again as well as the shortening and thickening of the chromatids. Centrioles move to the polar regions and arrange spindle fibers for the second meiotic division.
In metaphase II, the centromeres contain two kinetochores, that attach to spindle fibers from the centrosomes (centrioles) at each pole. The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plate.
This is followed by anaphase II, where the centromeres are cleaved, allowing microtubules attached to the kinetochores to pull the sister chromatids apart. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles.
The process ends with telophase II, which is similar to telophase I, and is marked by uncoiling and lengthening of the chromosomes and the disappearance of the spindle. Nuclear envelopes reform and cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes. Meiosis is now complete.
# The Significance of Meiosis
Meiosis facilitates stable sexual reproduction. Without the halving of ploidy, or chromosome count, fertilization would result in zygotes that have twice the number of chromosomes as the zygotes from the previous generation. Successive generations would have an exponential increase in chromosome count. In organisms that are normally diploid, polyploidy, the state of having three or more sets of chromosomes, results in developmental abnormalities or lethality [4]. Polyploidy is poorly tolerated in most animal species. Plants, however, regularly produce fertile, viable polyploids. Polyploidy has been implicated as an important mechanism in plant speciation.
Most importantly, recombination and independent assortment of homologous chromosomes allow for a greater diversity of genotypes in the population. This produces genetic variation in gametes that promote genetic and phenotypic variation in a population of offspring.
# Nondisjunction
The normal separation of chromosomes in meiosis I or sister chromatids in meiosis II is termed disjunction. When the separation is not normal, it is called nondisjunction. This results in the production of gametes which have either too many of too few of a particular chromosome, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis.
This is a cause of several medical conditions in humans (such as):
- Down Syndrome - trisomy of chromosome 21
- Patau Syndrome - trisomy of chromosome 13
- Edward Syndrome - trisomy of chromosome 18
- Klinefelter Syndrome - extra X chromosomes in males - ie XXY, XXXY, XXXXY
- Turner Syndrome - lacking of one X chromosome in females - ie XO
- Triple X syndrome - and extra X chromosome in females
- XYY Syndrome - an extra Y chromosome in males
# Meiosis in humans
In females, meiosis occurs in cells known as oogonia (singular: oogonium). Each oogonium that initiates meiosis will divide twice to form a single oocyte and three polar bodies. However, before these divisions occur, these cells stop at the diplotene stage of meiosis I and lay dormant within a protective shell of somatic cells called the follicle. Follicles begin growth at a steady pace in a process known as folliculogenesis, and a small number enter the menstrual cycle. Menstruated oocytes continue meiosis I and arrest at meiosis II until fertilization. The process of meiosis in females occurs during oogenesis, and differs from the typical meiosis in that it features a long period of meiotic arrest known as the Dictyate stage and lacks the assistance of centrosomes.
In males, meiosis occurs in precursor cells known as spermatogonia that divide twice to become sperm. These cells continuously divide without arrest in the seminiferous tubules of the testicles. Sperm is produced at a steady pace. The process of meiosis in males occurs during spermatogenesis. | https://www.wikidoc.org/index.php/Meiosis | |
5a50b32049482f09599a63e6e0230aebe6cd2254 | wikidoc | Melange | Melange
Melange is the name of the fictional drug (also known as spice) central to the Dune series of science fiction novels by Frank Herbert, and derivative works.
# Origin
In Dune, there is only one source of melange: the sands of the planet Arrakis, colloquially known as Dune. Melange is a geriatric drug that gives the user a longer lifespan, greater vitality, and heightened awareness; it can also unlock prescience in some subjects, depending upon the dosage and the consumer's physiology. Its use to enhance prescience makes interstellar travel possible. Melange is the most essential and valuable commodity in the universe. Its flavor strongly resembles that of cinnamon; however, each subsequent tasting reveals a different flavor.
A pre-spice mass is the precursor of melange; the mass is formed by the chemical alterations induced in water collected underground by sandtrout, the haploid forms of sandworms (although, it must be noted that some researchers have compared the spice, in its biological function among the sandworms, to sperm). These chemical processes produce gases, which build up until the mass explodes in what is known as a spice blow. This explosion kills most of the larvae and releases the melange onto the surface of the desert. Liet-Kynes describes one in Dune:
Then he heard the sand rumbling. Every Fremen knew the sound, could distinguish it immediately from the noises of worms or other desert life. Somewhere beneath him, the pre-spice mass had accumulated enough water and organic matter from the little makers, had reached the critical stage of wild growth. A gigantic bubble of carbon dioxide was forming deep in the sand, heaving upward in an enormous "blow" with a dust whirlpool at its center. It would exchange what had been formed deep in the sand for whatever lay on the surface.
Baron Harkonnen also witnesses one in the first chapter of Brian Herbert's House Atreides.
Collecting the melange is hazardous in the extreme, since rhythmic activity on the desert surface of Arrakis attracts the worms, which are four hundred meters in length on average, and very dangerous, capable of swallowing a mining crawler whole. Thus, the mining operation essentially consists of vacuuming it off the surface with a harvesting machine until a worm comes, at which time a carry-all aircraft lifts the mining vehicle to safety. The Fremen, who have learned to co-exist with the sandworms in the desert, harvest the spice manually for their own use and for smuggling off-planet.
Spice is in general use all over the universe, and is a sign of wealth. To ingest it is the ultimate display of conspicuous consumption. The planet Arrakis is central to the inhabited worlds of the universe because it is the sole source of spice.
Later, an artificial method of producing the spice is discovered by the Bene Tleilax, who develop in secret the technology to produce melange from axolotl tanks later in the series. It was not fully successful in pushing natural melange out of the market place.
# Use
Alia Atreides notes the importance of melange in Children of Dune:
Not without reason was the spice often called "the secret coinage." Without melange, the Spacing Guild's heighliners could not move. Melange precipitated the "navigation trance" by which a translight pathway could be "seen" before it was traveled. Without melange and its amplification of the human immunogenic system, life expectancy for the very rich degenerated by a factor of at least four. Even the vast middle class of the Imperium ate diluted melange in small sprinklings with at least one meal a day.
Although it is referred to as "spice" and can be mixed with food, melange is indeed a drug in the clinical sense, its use being physically addictive and having intense psychotropic effects. Spice is also a powerful entheogen, which suitably trained adepts can use to initiate clairvoyant and precognitive trances, and access racial memory. A melange user, once addicted, is thereafter compelled to continue using it for the rest of his or her life, as any discontinuation of its use will induce excruciating withdrawal symptoms, and if not quickly resumed, will invariably be followed by death. Taken daily, however, melange can extend its user's lifespan by hundreds of years. Due to its rarity and value, and its necessity as a catalyst for interstellar travel, the group controlling spice production on Dune controls the fate of the Empire, a form of hydraulic despotism. Melange serves as the axis about which the human universe turns, it being required for space travel, and with most elites addicted to (and living much longer because of) the drug.
## Use by navigators
The Navigators of the Spacing Guild depend upon melange for the heightened awareness and the prescient ability to see safe paths through space-time, allowing them to navigate the gigantic Guild Heighliners between planets. They exist within a cloud of melange in a tank; this extended exposure warps their bodies into a grotesque neotenic parody of a human fish.
## Use by Bene Gesserit
The Bene Gesserit use "spice essence", the toxic substance that can be converted to melange, for the ritual known as the Spice agony, an ordeal in which an acolyte deliberately imbibes a massive overdose and confronts her inner-self and the selves of all her female ancestors. If she masters the confrontation, she emerges as a Reverend Mother, a Bene Gesserit of terrifying abilities, fully in command of her Other Memories, the collective egos of her female ancestors. The process is fatal to those not strong enough. It is said that no male has ever survived this process other than Paul Atreides and his son, Leto II.
# Physiological side effects
Extensive use of the drug tints the sclera, cornea and iris of the user to a dark shade of blue, called "blue-in-blue" or "the Eyes of Ibad," which is something of a source of pride amongst the Fremen and a symbol of their tribal bond. Paul Atreides, the main character in the original Dune novel, initially has green eyes, but after several years on Arrakis his eyes begin to take on the deep, uniform blue of the Fremen. On other planets, the addicted often use tinted contact lenses to hide this discoloration. In Dune, Paul sees two Guildsmen and notes:
The taller of the two, though, held a hand to his left eye. As the Emperor watched, someone jostled the Guildsman's arm, the hand moved, and the eye was revealed. The man had lost one of his masking contact lenses, and the eye stared out a total blue so dark as to be almost black.
# Quotes
- "He who controls the spice controls the universe."
- "The spice must flow."
- "In this time, the most precious substance in the universe is the spice melange. The spice extends life. The spice expands consciousness."
# Notes
- ↑ In Children of Dune it is noted that "Farad'n touched his own eyelids, feeling the hard surfaces of the permanent contact lenses which concealed the total blue of his spice addiction."
- ↑ In Heretics of Dune, the Bene Gesserit Schwangyu notes that "Blue-in-blue eyes uncorrected by any lens gave Lucilla a piercing expression that went with her long oval face." Herbert later writes of Duncan Idaho that "His first glimpse of Schwangyu had confronted him with eyes concealed behind contact lenses that simulated non-addict pupils and slightly bloodshot whites." | Melange
Melange is the name of the fictional drug (also known as [the] spice) central to the Dune series of science fiction novels by Frank Herbert, and derivative works.
# Origin
In Dune, there is only one source of melange: the sands of the planet Arrakis, colloquially known as Dune. Melange is a geriatric drug that gives the user a longer lifespan, greater vitality, and heightened awareness; it can also unlock prescience in some subjects, depending upon the dosage and the consumer's physiology. Its use to enhance prescience makes interstellar travel possible. Melange is the most essential and valuable commodity in the universe. Its flavor strongly resembles that of cinnamon; however, each subsequent tasting reveals a different flavor.
A pre-spice mass is the precursor of melange; the mass is formed by the chemical alterations induced in water collected underground by sandtrout, the haploid forms of sandworms (although, it must be noted that some researchers have compared the spice, in its biological function among the sandworms, to sperm). These chemical processes produce gases, which build up until the mass explodes in what is known as a spice blow. This explosion kills most of the larvae and releases the melange onto the surface of the desert. Liet-Kynes describes one in Dune:
Then he heard the sand rumbling. Every Fremen knew the sound, could distinguish it immediately from the noises of worms or other desert life. Somewhere beneath him, the pre-spice mass had accumulated enough water and organic matter from the little makers, had reached the critical stage of wild growth. A gigantic bubble of carbon dioxide was forming deep in the sand, heaving upward in an enormous "blow" with a dust whirlpool at its center. It would exchange what had been formed deep in the sand for whatever lay on the surface.
Baron Harkonnen also witnesses one in the first chapter of Brian Herbert's House Atreides.
Collecting the melange is hazardous in the extreme, since rhythmic activity on the desert surface of Arrakis attracts the worms, which are four hundred meters in length on average, and very dangerous, capable of swallowing a mining crawler whole. Thus, the mining operation essentially consists of vacuuming it off the surface with a harvesting machine until a worm comes, at which time a carry-all aircraft lifts the mining vehicle to safety. The Fremen, who have learned to co-exist with the sandworms in the desert, harvest the spice manually for their own use and for smuggling off-planet.
Spice is in general use all over the universe, and is a sign of wealth. To ingest it is the ultimate display of conspicuous consumption. The planet Arrakis is central to the inhabited worlds of the universe because it is the sole source of spice.
Later, an artificial method of producing the spice is discovered by the Bene Tleilax, who develop in secret the technology to produce melange from axolotl tanks later in the series. It was not fully successful in pushing natural melange out of the market place.
# Use
Alia Atreides notes the importance of melange in Children of Dune:
Not without reason was the spice often called "the secret coinage." Without melange, the Spacing Guild's heighliners could not move. Melange precipitated the "navigation trance" by which a translight pathway could be "seen" before it was traveled. Without melange and its amplification of the human immunogenic system, life expectancy for the very rich degenerated by a factor of at least four. Even the vast middle class of the Imperium ate diluted melange in small sprinklings with at least one meal a day.
Although it is referred to as "spice" and can be mixed with food, melange is indeed a drug in the clinical sense, its use being physically addictive and having intense psychotropic effects. Spice is also a powerful entheogen, which suitably trained adepts can use to initiate clairvoyant and precognitive trances, and access racial memory. A melange user, once addicted, is thereafter compelled to continue using it for the rest of his or her life, as any discontinuation of its use will induce excruciating withdrawal symptoms, and if not quickly resumed, will invariably be followed by death. Taken daily, however, melange can extend its user's lifespan by hundreds of years. Due to its rarity and value, and its necessity as a catalyst for interstellar travel, the group controlling spice production on Dune controls the fate of the Empire, a form of hydraulic despotism. Melange serves as the axis about which the human universe turns, it being required for space travel, and with most elites addicted to (and living much longer because of) the drug.
## Use by navigators
The Navigators of the Spacing Guild depend upon melange for the heightened awareness and the prescient ability to see safe paths through space-time, allowing them to navigate the gigantic Guild Heighliners between planets. They exist within a cloud of melange in a tank; this extended exposure warps their bodies into a grotesque neotenic parody of a human fish.
## Use by Bene Gesserit
The Bene Gesserit use "spice essence", the toxic substance that can be converted to melange, for the ritual known as the Spice agony, an ordeal in which an acolyte deliberately imbibes a massive overdose and confronts her inner-self and the selves of all her female ancestors. If she masters the confrontation, she emerges as a Reverend Mother, a Bene Gesserit of terrifying abilities, fully in command of her Other Memories, the collective egos of her female ancestors. The process is fatal to those not strong enough. It is said that no male has ever survived this process other than Paul Atreides and his son, Leto II.
# Physiological side effects
Extensive use of the drug tints the sclera, cornea and iris of the user to a dark shade of blue, called "blue-in-blue" or "the Eyes of Ibad," which is something of a source of pride amongst the Fremen and a symbol of their tribal bond. Paul Atreides, the main character in the original Dune novel, initially has green eyes, but after several years on Arrakis his eyes begin to take on the deep, uniform blue of the Fremen. On other planets, the addicted often use tinted contact lenses to hide this discoloration.[1][2] In Dune, Paul sees two Guildsmen and notes:
The taller of the two, though, held a hand to his left eye. As the Emperor watched, someone jostled the Guildsman's arm, the hand moved, and the eye was revealed. The man had lost one of his masking contact lenses, and the eye stared out a total blue so dark as to be almost black.
# Quotes
- "He who controls the spice controls the universe."
- "The spice must flow."
- "In this time, the most precious substance in the universe is the spice melange. The spice extends life. The spice expands consciousness."
# Notes
- ↑ In Children of Dune it is noted that "Farad'n touched his own eyelids, feeling the hard surfaces of the permanent contact lenses which concealed the total blue of his spice addiction."
- ↑ In Heretics of Dune, the Bene Gesserit Schwangyu notes that "Blue-in-blue eyes uncorrected by any lens gave Lucilla a piercing expression that went with her long oval face." Herbert later writes of Duncan Idaho that "His first glimpse of Schwangyu had confronted him with eyes concealed behind contact lenses that simulated non-addict pupils and slightly bloodshot whites." | https://www.wikidoc.org/index.php/Melange | |
e6bdc0619b40f90d4a83f229a3453450941c06bf | wikidoc | Melting | Melting
Melting is a process that results in the phase change of a substance from a solid to a liquid. The internal energy of a solid substance is increased (typically by the application of heat) to a specific temperature (called the melting point) at which it changes to the liquid phase. An object that has melted completely is molten.
The melting point of a substance is a characteristic property. The melting point may not be equal to the freezing point. This is evident in the phenomenon known as supercooling. In the case of water, ice crystals typically require a seed on which to begin formation. Water on a very clean glass surface will often supercool several degrees below the melting point without freezing. Fine emulsions of pure water have been cooled to -38 degrees celsius without the nucleation of ice taking place. For this reason, melting point is a characteristic property of a substance while freezing point is not.
# Molecular vibrations
When the internal energy of a gas is increased by the application of an external energy source, the molecular vibrations of the substance increases. As these vibrations increase, the substance becomes more and more ordered. Fusion is also another term used for this.
# Constant temperature
Substances melt at a constant temperature, the melting point. Further increases in temperature (even with continued application of energy) do not occur until the substance is molten.
# The thermodynamics of melting
From a thermodynamics point of view, at the melting point the change in Gibbs free energy (\Delta G) of the Material is zero, because the enthalpy (H) and the entropy (S) of the material are increasing (\Delta H, \Delta S > 0). Melting phenomenon happens when the Gibbs free energy of the liquid becomes lower than the solid for that material. At various pressures this happens at a specific temperature. It can also be shown that:
\Delta S = \frac {\Delta H} {T}
The "T","\Delta S", and "\Delta H" in the above are respectively the temperature at the melting point, change of entropy of melting, and the change of enthalpy of melting.
# Books
- Kleinert, Hagen, Gauge Fields in Condensed Matter, Vol. II, "STRESSES AND DEFECTS; Differential Geometry, Crystal Melting", pp. 743-1456, World Scientific (Singapore, 1989); Paperback ISBN 9971-5-0210-0 (readable online here)
# Other meanings
In genetics, melting DNA means to separate the double-stranded DNA into two single strands by heating or the use of chemicals.which means that your dna is made of two different parts | Melting
Melting is a process that results in the phase change of a substance from a solid to a liquid. The internal energy of a solid substance is increased (typically by the application of heat) to a specific temperature (called the melting point) at which it changes to the liquid phase. An object that has melted completely is molten.
The melting point of a substance is a characteristic property. The melting point may not be equal to the freezing point. This is evident in the phenomenon known as supercooling. In the case of water, ice crystals typically require a seed on which to begin formation. Water on a very clean glass surface will often supercool several degrees below the melting point without freezing. Fine emulsions of pure water have been cooled to -38 degrees celsius without the nucleation of ice taking place. For this reason, melting point is a characteristic property of a substance while freezing point is not.
# Molecular vibrations
When the internal energy of a gas is increased by the application of an external energy source, the molecular vibrations of the substance increases. As these vibrations increase, the substance becomes more and more ordered. Fusion is also another term used for this.
# Constant temperature
Substances melt at a constant temperature, the melting point. Further increases in temperature (even with continued application of energy) do not occur until the substance is molten.
# The thermodynamics of melting
From a thermodynamics point of view, at the melting point the change in Gibbs free energy (<math>\Delta G</math>) of the Material is zero, because the enthalpy (<math>H</math>) and the entropy (<math>S</math>) of the material are increasing (<math>\Delta H, \Delta S > 0</math>). Melting phenomenon happens when the Gibbs free energy of the liquid becomes lower than the solid for that material. At various pressures this happens at a specific temperature. It can also be shown that:
<math>\Delta S = \frac {\Delta H} {T}</math>
The "<math>T</math>","<math>\Delta S</math>", and "<math>\Delta H</math>" in the above are respectively the temperature at the melting point, change of entropy of melting, and the change of enthalpy of melting.
# Books
- Kleinert, Hagen, Gauge Fields in Condensed Matter, Vol. II, "STRESSES AND DEFECTS; Differential Geometry, Crystal Melting", pp. 743-1456, World Scientific (Singapore, 1989); Paperback ISBN 9971-5-0210-0 (readable online here)
# Other meanings
Template:Wiktionarypar
In genetics, melting DNA means to separate the double-stranded DNA into two single strands by heating or the use of chemicals.which means that your dna is made of two different parts | https://www.wikidoc.org/index.php/Melting | |
fa74a84954b04e5fb567dc2eccc920335fae4771 | wikidoc | Mesozoa | Mesozoa
The Mesozoa are enigmatic, minuscule, worm-like parasites. It is still unclear as to whether they are degenerate platyhelminthes (flatworms) or truly-primitive, basal metazoans. Generally, these tiny, elusive creatures consist of a somatoderm (outer layer) of ciliated cells surrounding one or more reproductive cells. Decades ago, Mesozoa was classified as a phylum. But molecular phylogeny studies have shown that the mysterious mesozoans are polyphyletic. That is, they consist of two unrelated groups.
As a result of these recent findings in molecular biology, the label mesozoan is now often applied informally, rather than as a formal taxon. Some workers previously classified Mesozoa as the sole phylum of the lonely subkingdom Agnotozoa.
# Life cycle
Mesozoa have complex life cycles alternating between asexual and sexual generations. In the nephridia of a cephalopod are numerous wormlike organisms (nematogens) that are composed of a fixed number of somatic cells. Within the center of the nematogens are axial cells. These cells give rise to new nematogens. The nematogens turn into rhombogens to prepare for sexual development.
Sexual development begins in the axial cell of the rhombogen in an area called the infusorigen. Here, the amoeboid sperm develops. The jacket cells turn into eggs. Sperm emerges from the axial cell and fuses with the egg forming an infusoriform larva. The larva then crawls out. Eventually, the octopus is infected again by the young vermiform (worm-like) stage.
# Evolution
Mesozoa were once thought to be evolutionary intermediate forms between Protozoans and Metazoans, but now they are thought to be degenerate or simplified metazoa. Their ciliated larva are similar to the miracidium of trematodes, and their internal multiplication is similar to what happens in the sprocysts of trematodes. Mesozoan DNA has a low GC-content (40%). This amount is similar to ciliates, but ciliates tend to be binucleate. Others relate mesozoa to a group including annelids, planarians, and nemerteans.
# Groupings
The two main mesozoan groups are the Rhombozoa and the Orthonectida.
Other groups sometimes included in the Mesozoa are the Placozoa and the Monoblastozoa.
Monoblastozoans consist of a single description written in the 19th century of a species that has not been seen since. As such, many workers doubt that they are a real group.
As described, the animal had only a single layer of tissue.
## Rhombozoan mesozoans
Rhombozoa, or dicyemid mesozoans, are found in the nephridia (kidneys) of cephalopods (squid and octopuses). They range from a few millimeters long with twenty to thirty cells that include anterior attachment cells and a long central reproductive cell called an axial cell. This axial cell may develop asexually into vermiform juveniles or it may produce eggs and sperm that self-fertilize to produce a ciliated infusiform larva.
There are three genera: dicyema, pseudicyema, and dicyemennea.
## Orthonectid mesozoans
Orthonectida are found in the body spaces of various marine invertebrates including tissue spaces, gonads, genitorespiratory bursae. This pathogen causes host castration of different species.
The best known of Orthonectida is the parasite of brittle stars. The multinucleate syncytial stage lives within tissues and spaces of the gonad but can spread into arms. It causes the destruction of starfish ovary and eggs to cause castration (the male gonads are usually unaffected). The stages of the plasmodium develop into more plasmodia by simple fragmentation; at some point, they decide to go sexual. The syncytia are monoecious (either male or female), but young syncytia can fuse to produce both male and female. The males are ciliated and smaller than the females. The females and the males leave the starfish and mate in the sea. Tailed sperm enters the female and fertilizes the numerous oocytes. Each oocyst produces a small ciliated larva which makes way to another star. | Mesozoa
The Mesozoa are enigmatic, minuscule, worm-like parasites. It is still unclear as to whether they are degenerate platyhelminthes (flatworms) or truly-primitive, basal metazoans. Generally, these tiny, elusive creatures consist of a somatoderm (outer layer) of ciliated cells surrounding one or more reproductive cells. Decades ago, Mesozoa was classified as a phylum. But molecular phylogeny studies have shown that the mysterious mesozoans are polyphyletic. That is, they consist of two unrelated groups.[1]
As a result of these recent findings in molecular biology, the label mesozoan is now often applied informally, rather than as a formal taxon. Some workers previously classified Mesozoa as the sole phylum of the lonely subkingdom Agnotozoa.
# Life cycle
Mesozoa have complex life cycles alternating between asexual and sexual generations. In the nephridia of a cephalopod are numerous wormlike organisms (nematogens) that are composed of a fixed number of somatic cells. Within the center of the nematogens are axial cells. These cells give rise to new nematogens. The nematogens turn into rhombogens to prepare for sexual development.
Sexual development begins in the axial cell of the rhombogen in an area called the infusorigen. Here, the amoeboid sperm develops. The jacket cells turn into eggs. Sperm emerges from the axial cell and fuses with the egg forming an infusoriform larva. The larva then crawls out. Eventually, the octopus is infected again by the young vermiform (worm-like) stage.
# Evolution
Mesozoa were once thought to be evolutionary intermediate forms between Protozoans and Metazoans, but now they are thought to be degenerate or simplified metazoa. Their ciliated larva are similar to the miracidium of trematodes, and their internal multiplication is similar to what happens in the sprocysts of trematodes. Mesozoan DNA has a low GC-content (40%). This amount is similar to ciliates, but ciliates tend to be binucleate. Others relate mesozoa to a group including annelids, planarians, and nemerteans.
# Groupings
The two main mesozoan groups are the Rhombozoa and the Orthonectida.
Other groups sometimes included in the Mesozoa are the Placozoa and the Monoblastozoa.
Monoblastozoans consist of a single description written in the 19th century of a species that has not been seen since. As such, many workers doubt that they are a real group.[2]
As described, the animal had only a single layer of tissue.
[3]
## Rhombozoan mesozoans
Rhombozoa, or dicyemid mesozoans, are found in the nephridia (kidneys) of cephalopods (squid and octopuses). They range from a few millimeters long with twenty to thirty cells that include anterior attachment cells and a long central reproductive cell called an axial cell. This axial cell may develop asexually into vermiform juveniles or it may produce eggs and sperm that self-fertilize to produce a ciliated infusiform larva.
There are three genera: dicyema, pseudicyema, and dicyemennea.
## Orthonectid mesozoans
Orthonectida are found in the body spaces of various marine invertebrates including tissue spaces, gonads, genitorespiratory bursae. This pathogen causes host castration of different species.
The best known of Orthonectida is the parasite of brittle stars. The multinucleate syncytial stage lives within tissues and spaces of the gonad but can spread into arms. It causes the destruction of starfish ovary and eggs to cause castration (the male gonads are usually unaffected). The stages of the plasmodium develop into more plasmodia by simple fragmentation; at some point, they decide to go sexual. The syncytia are monoecious (either male or female), but young syncytia can fuse to produce both male and female. The males are ciliated and smaller than the females. The females and the males leave the starfish and mate in the sea. Tailed sperm enters the female and fertilizes the numerous oocytes. Each oocyst produces a small ciliated larva which makes way to another star. | https://www.wikidoc.org/index.php/Mesozoa | |
3e6951177681ccf0b6eef7c3c2f66ab80c592131 | wikidoc | miR-134 | miR-134
miR-134 is a family of microRNA precursors found in mammals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-134 precursor is the microRNA mir-134.
miR-134 was one of a number of microRNAs found to be increasingly expressed in schizophrenia.
# Functions
miR-134 is a brain-specific microRNA; in rats it is localised specifically in hippocampal neurons and may indirectly regulate synaptic development through antisense pairing with LIMK1 mRNA. In the human brain, SIRT1 is thought to mediate CREB protein through miR-134, giving the microRNA a role in higher brain functions such a memory formation.
miR-134 has also been reported to function in mouse embryonic stem cells as part of a complex network regulating their differentiation.
# Applications
miR-134 levels in circulating blood could potentially be used as a peripheral biomarker for bipolar disorder. | miR-134
miR-134 is a family of microRNA precursors found in mammals, including humans.[1] MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product.[2] The excised region or, mature product, of the miR-134 precursor is the microRNA mir-134.
miR-134 was one of a number of microRNAs found to be increasingly expressed in schizophrenia.[3]
# Functions
miR-134 is a brain-specific microRNA; in rats it is localised specifically in hippocampal neurons and may indirectly regulate synaptic development through antisense pairing with LIMK1 mRNA.[4][5] In the human brain, SIRT1 is thought to mediate CREB protein through miR-134, giving the microRNA a role in higher brain functions such a memory formation.[6]
miR-134 has also been reported to function in mouse embryonic stem cells as part of a complex network regulating their differentiation.[7]
# Applications
miR-134 levels in circulating blood could potentially be used as a peripheral biomarker for bipolar disorder.[8] | https://www.wikidoc.org/index.php/MiR-134 | |
858732c048fbab2f212756aecd8fe193cc62823b | wikidoc | miR-138 | miR-138
miR-138 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.
miR-138 has been used as an example of the post-transcriptional regulation of miRNA, due to the finding that while the precursor is expressed ubiquitously, the mature product is found only in specific cell types.
# Species distribution
The presence of miR-138 has been detected experimentally in humans (Homo sapiens) and in different animals including house mouse (Mus musculus), brown rat (Rattus norvegicus), platypus (Ornithorhynchus anatinus), Carolina anole(Anolis carolinensis), cattle (Bos taurus), common carp (Cyprinus carpio), dog (Canis familiaris), Chinese hamster (Cricetulus griseus), zebrafish (Danio rerio), red junglefowl (Gallus gallus), western gorilla (Gorilla gorilla), gray short-tailed opossum (Monodelphis domestica), Oryzias latipes, sea lamprey (Petromyzon marinus), Tasmanian devil (Sarcophilus harrisii), wild boar (Sus scrofa) and zebra finch (Taeniopygia guttata).
It is also predicted computationally that the miR-138 gene exists in the genome of other animals including horse (Equus caballus), rhesus macaque (Macaca mulatta), takifugu rubripes (Fugu rubripes), Bornean orangutan (Pongo pygmaeus), common chimpanzee (Pan troglodytes), Tetraodon nigroviridis and western clawed frog (Xenopus tropicalis).
# Genomic location
In human genome, there are two miR-138 associated genes and they are not located in any cluster. More precisely, the miR-138-1 gene is in region 5 at 3p21.3 and miR-138-2 is located on chromosome 16 (16q13).
# Pattern of expression
In adult mice, miR-138 is only expressed in brain tissue. Its expression is not uniform throughout the brain but restricted to distinct neuronal populations. On the contrary, its precursor, pre-miR-138-2, is ubiquitously expressed throughout all tissues, which suggests that the expression of miRNAs can be regulated at the post-transcription level.
In the zebrafish, miR-138 is expressed in specific domains in the heart and is required to establish appropriate chamber-specific gene expression patterns.
# Targets and function
Since the identification of miR-138, a number of targets have been found and some of them have been verified experimentally. It has been proven that miR-138 is involved in different pathways. Furthermore, it is in relation with various types of cancer. | miR-138
miR-138 is a family of microRNA precursors found in animals, including humans.[1] MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product.[2] The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.
miR-138 has been used as an example of the post-transcriptional regulation of miRNA, due to the finding that while the precursor is expressed ubiquitously, the mature product is found only in specific cell types.[3]
# Species distribution
The presence of miR-138 has been detected experimentally in humans (Homo sapiens)[1][4][5] and in different animals including house mouse (Mus musculus),[1][3][4][6][7][8][9] brown rat (Rattus norvegicus),[1][7][10][11][12] platypus (Ornithorhynchus anatinus),[13] Carolina anole(Anolis carolinensis),[14] cattle (Bos taurus),[15][16] common carp (Cyprinus carpio),[17] dog (Canis familiaris),[18] Chinese hamster (Cricetulus griseus),[19] zebrafish (Danio rerio),[20] red junglefowl (Gallus gallus),[21] western gorilla (Gorilla gorilla),[22] gray short-tailed opossum (Monodelphis domestica),[23] Oryzias latipes,[24] sea lamprey (Petromyzon marinus),[25] Tasmanian devil (Sarcophilus harrisii),[26] wild boar (Sus scrofa)[27] and zebra finch (Taeniopygia guttata).[28]
It is also predicted computationally that the miR-138 gene exists in the genome of other animals including horse (Equus caballus),[29] rhesus macaque (Macaca mulatta),[30] takifugu rubripes (Fugu rubripes), Bornean orangutan (Pongo pygmaeus),[31] common chimpanzee (Pan troglodytes),[32] Tetraodon nigroviridis and western clawed frog (Xenopus tropicalis).
# Genomic location
In human genome, there are two miR-138 associated genes and they are not located in any cluster. More precisely, the miR-138-1 gene is in region 5 at 3p21.3[33] and miR-138-2 is located on chromosome 16 (16q13).[34]
# Pattern of expression
In adult mice, miR-138 is only expressed in brain tissue. Its expression is not uniform throughout the brain but restricted to distinct neuronal populations. On the contrary, its precursor, pre-miR-138-2, is ubiquitously expressed throughout all tissues, which suggests that the expression of miRNAs can be regulated at the post-transcription level.[3]
In the zebrafish, miR-138 is expressed in specific domains in the heart and is required to establish appropriate chamber-specific gene expression patterns.[35]
# Targets and function
Since the identification of miR-138, a number of targets have been found and some of them have been verified experimentally. It has been proven that miR-138 is involved in different pathways. Furthermore, it is in relation with various types of cancer. | https://www.wikidoc.org/index.php/MiR-138 | |
7706ab4685b1e1b4a2f50435d1eb0feec48eafc7 | wikidoc | miR-144 | miR-144
miR-144 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. In humans, miR-144 has been characterised as a "common miRNA signature" of a number of different tumours.
GATA4 is thought to activate transcription of the miR-144 microRNA precursor.
# Function
miR-144 functions in a cluster with miR-451. This locus regulates the expression of a number of genes whose products are involved in erythropoiesis. One of the identified targets of miR-144 is insulin receptor substrate 1.
# Applications
miR-144 has been identified as one of a number of potential miRNA targets which could be used to treat schizophrenia and bipolar affective disorder. It has also been suggested as a potential therapeutic tool to treat ischemic heart disease. | miR-144
miR-144 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] In humans, miR-144 has been characterised as a "common miRNA signature"[2] of a number of different tumours.
GATA4 is thought to activate transcription of the miR-144 microRNA precursor.[3]
# Function
miR-144 functions in a cluster with miR-451. This locus regulates the expression of a number of genes whose products are involved in erythropoiesis.[4] One of the identified targets of miR-144 is insulin receptor substrate 1.[5]
# Applications
miR-144 has been identified as one of a number of potential miRNA targets which could be used to treat schizophrenia and bipolar affective disorder.[6] It has also been suggested as a potential therapeutic tool to treat ischemic heart disease.[3] | https://www.wikidoc.org/index.php/MiR-144 | |
540ad9763ccb9de84927cf0a42fa07555910a515 | wikidoc | miR-146 | miR-146
miR-146 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
miR-146 is primarily involved in the regulation of inflammation and other process that function in the innate immune system. Loss of functional miR-146 (and mir-145) could predispose an individual to suffer from chromosome 5q deletion syndrome. miR-146 has also been reported to be highly upregulated in osteoarthritis cartilage, and could be involved in its pathogenesis. mir-146 expression is associated with survival in triple negative breast cancer.
# Function
miR-146 is thought to be a mediator of inflammation along with another microRNA, mir-155. The expression of miR-146 is upregulated by inflammatory factors such as interleukin 1 and tumor necrosis factor-alpha. miR-146 dysregulates a number of targets which are mostly involved in toll-like receptor pathways that bring about a cytokine response as part of the innate immune system. miR-146 operates in a feedback system or "negative regulatory loop" to finely tune inflammatory responses.
# Applications
miR-146 could be used as a biomarker for sepsis. In addition it was found to be absent from the exosomes of prion infected cells suggesting it could be used as a biomarker for prion infection. miR-146a could be targeted therapeutically as its depletion has implication in the hyperactive response to infection. | miR-146
miR-146 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
miR-146 is primarily involved in the regulation of inflammation and other process that function in the innate immune system.[3] Loss of functional miR-146 (and mir-145) could predispose an individual to suffer from chromosome 5q deletion syndrome.[4] miR-146 has also been reported to be highly upregulated in osteoarthritis cartilage, and could be involved in its pathogenesis.[5] mir-146 expression is associated with survival in triple negative breast cancer.[6]
# Function
miR-146 is thought to be a mediator of inflammation along with another microRNA, mir-155. The expression of miR-146 is upregulated by inflammatory factors such as interleukin 1 and tumor necrosis factor-alpha.[7] miR-146 dysregulates a number of targets which are mostly involved in toll-like receptor pathways that bring about a cytokine response as part of the innate immune system.[3][7] miR-146 operates in a feedback system or "negative regulatory loop"[8] to finely tune inflammatory responses.[4]
# Applications
miR-146 could be used as a biomarker for sepsis.[9] In addition it was found to be absent from the exosomes of prion infected cells suggesting it could be used as a biomarker for prion infection.[10] miR-146a could be targeted therapeutically as its depletion has implication in the hyperactive response to infection.[11] | https://www.wikidoc.org/index.php/MiR-146 | |
b35dd47c3e385d9305176cafe6424fb08d1bf7b5 | wikidoc | miR-150 | miR-150
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miR-150 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
miR-150 functions in hematopoiesis; it regulates genes whose downstream products encourage differentiating stem cells towards becoming megakaryocytes rather than erythrocytes. It is also thought to control B and T cell differentiation, alongside mir-155.
# Role in cancer
miR-150 has been linked with a number of cancers. It is thought to promote cancer cell proliferation in gastric cancer and has also been found to be more than 50x overexpressed in osteosarcoma.
# Applications
miR-150 levels in blood plasma can be indicative of early sepsis; it could have a future use therapeutically in treating the condition. In addition, miR-150 is one of a number of microRNAs whose expression profile could be used as a biomarker of hepatocellular carcinoma. | miR-150
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miR-150 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
miR-150 functions in hematopoiesis; it regulates genes whose downstream products encourage differentiating stem cells towards becoming megakaryocytes rather than erythrocytes.[3][4] It is also thought to control B and T cell differentiation, alongside mir-155.[5][6]
# Role in cancer
miR-150 has been linked with a number of cancers. It is thought to promote cancer cell proliferation in gastric cancer and has also been found to be more than 50x overexpressed in osteosarcoma.[7]
# Applications
miR-150 levels in blood plasma can be indicative of early sepsis; it could have a future use therapeutically in treating the condition.[8] In addition, miR-150 is one of a number of microRNAs whose expression profile could be used as a biomarker of hepatocellular carcinoma.[9] | https://www.wikidoc.org/index.php/MiR-150 | |
e97d1d42206894f4adc032511f5d92f9b6c08db1 | wikidoc | miR-155 | miR-155
MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.
# Discovery
The MIR155HG was initially identified as a gene that was transcriptionally activated by promoter insertion at a common retroviral integration site in B-cell lymphomas and was formerly called BIC (B-cell Integration Cluster). The MIR155HG is transcribed by RNA polymerase II and the resulting ~1,500 nucleotide RNA is capped and polyadenylated. The 23 nucleotide single-stranded miR-155, which is harbored in exon 3, is subsequently processed from the parent RNA molecule.
# Biogenesis
The MIR155HG RNA transcript does not contain a long open reading frame (ORF), however, it does include an imperfectly base-paired stem loop that is conserved across species. This non-coding RNA (ncRNA) is now defined as a primary-miRNA (pri-miRNA). Once miR-155 pri-miRNA is transcribed, this transcript is cleaved by the nuclear microprocessor complex, of which the core components are the RNase III type endonuclease Drosha and the DiGeorge critical region 8 (DGCR8) protein, to produce a 65 nucleotide stem-loop precursor miRNA (pre-mir-155) (see Figure 2).
Following export from the nucleus by exportin-5, pre-mir-155 molecules are cleaved near the terminal loop by Dicer resulting in RNA duplexes of ~22nucleotides. Following Dicer cleavage, an Argonaute (Ago) protein binds to the short RNA duplexes, forming the core of a multi-subunit complex called the RNA-induced silencing complex (RISC). In a manner similar to siRNA duplexes, one of the two strands, the "passenger miRNA" (miR-155*), is released and degraded while the other strand, designated the "guide strand" or "mature miRNA" (miR-155), is retained within the RISC.
Recent data suggest that both arms of the pre-miRNA hairpin can give rise to mature miRNAs. Due to the increasing number of examples where two functional mature miRNAs are processed from opposite arms of the same pre-miRNA, pre-mir-155 products are now denoted with the suffix -5p (from the 5′ arm) (e.g. miR-155-5p) and -3p (from the 3′ arm) (e.g. miR-155-3p) following their name (see Figure 3).
Once miR-155-5p/-3p is assembled into the RISC, these molecules subsequently recognize their target messenger RNA (mRNA) by base pairing interactions between nucleotides 2 and 8 of miR-155-5p/-3p (the seed region) and complementary nucleotides predominantly in the 3'-untranslated region (3'-UTR) of mRNAs (see Figure 4 and 5 below). Finally, with the miR-155-5p/-3p acting as an adaptor for the RISC, complex-bound mRNAs are subjected to translational repression (i.e. inhibition of translation initiation) and/or degradation following deadenylation.
# Evolutionary conservation
Early phylogenetic analyses demonstrated that the sequence of pre-mir-155 and miR-155-5p was conserved between human, mouse, and chicken. Recent annotated sequencing data found that 22 different organisms including, mammals, amphibians, birds, reptiles, sea squirts, and sea lampreys, express a conserved miR-155-5p. Currently much less sequence data is available regarding miR-155-3p, therefore, it is not clear how conserved this miRNA is across species.
# Tissue distribution
Northern blot analysis found that miR-155 pri-miRNA was abundantly expressed in the human spleen and thymus and detectable in the liver, lung, and kidney. Subsequently, polymerase chain reaction (PCR) experiments demonstrated that miR-155-5p was detectable in all human tissues investigated. Sequence analysis of small RNA clone libraries comparing miRNA expression to all other organ systems examined established that miR-155-5p was one of five miRNAs (i.e. miR-142, miR-144, miR-150, miR-155, and miR-223) that was specific for hematopoietic cells including B-cells, T-cells, monocytes and granulocytes. Together these results suggest that miR-155-5p is expressed in a number of tissues and cell types and, therefore, may play a critical role in a wide variety of biological processes, including hematopoiesis
Although very few studies have investigated the expression levels of miR-155-3p, Landgraf et al. established that expression levels of this miRNA was very low in hematopoietic cells. Additionally, PCR analyses found that while miR-155-3p was detectable in a number of human tissues the expression levels of this miRNA were 20-200 fold less when compared to miR-155-5p levels. Even though the function of miR-155-3p has been largely ignored, several studies now suggest that, in some cases (astrocytes and plasmacytoid dendritic cells), both miR-155-5p and -3p can be functionally matured from pre-mir-155.
# Targets
Bioinformatic analysis using TargetScan 6.2 (release date June, 2012) revealed at least 4,174 putative human miR-155-5p mRNA targets exist, with a total of 918 conserved sites (i.e. between mouse and human) and 4,249 poorly conserved sites (i.e. human only). Although the TargetScan 6.2 algorithm cannot be utilized to determine the miR-155-3p putative targets, one would speculate that this miRNA may also potentially regulate the expression of thousands of mRNA targets.
A comprehensive list of miR-155-5p/mRNA targets that were experimentally authenticated by both the demonstration of endogenous transcript regulation by miR-155-5p and validation of the miR-155-5p seed sequence through a reporter assay was recently assembled. This list included 140 genes and included regulatory proteins for myelopoiesis and leukemogenesis (e.g. SHIP-1, AICDA, ETS1, JARID2, SPI1, etc.), inflammation (e.g. BACH1, FADD, IKBKE, INPP5D, MYD88, RIPK1, SPI1, SOCS, etc.) and known tumor suppressors (e.g. CEBPβ, IL17RB, PCCD4, TCF12, ZNF652, etc.). The validated miR-155-5p binding site harbored in the SPI1 mRNA and the validated miR-155-3p binding site harbored in the IRAK3 mRNA are shown in Figures 4 and 5 respectively.
# Physiological roles
## Hematopoiesis
Hematopoiesis is defined as the formation and development of blood cells, all of which are derived from hematopoietic stem-progenitor cells (HSPCs). HSPCs are primitive cells capable of self-renewal and initially differentiate into common myeloid progenitor (CMP) or common lymphoid progenitor (CLP) cells. CMPs represent the cellular population that has become myeloid lineage and it is the point that myelopoeisis begins. During myelopoeisis further cellular differentiation takes place including thrombopoiesis, erythropoeisis, granulopoeisis, and monocytopoeisis. CLPs subsequently differentiate into B-cells and T-cells in a process designated lymphopoiesis. Given that miR-155-5p is expressed in hematopoietic cells it was hypothesized that this miRNA plays a critical role in these cellular differentiation processes. In support of this premise, miR-155-5p was found to be expressed in CD34(+) human HSPCs, and it was speculated that this miRNA may hold these cells at an early stem-progenitor stage, inhibiting their differentiation into a more mature cell (i.e. megakaryocytic/erythroid/granulocytic/monocytic/B-lymphoid/T-lymphoid). This hypothesis was substantiated when pre-mir-155 transduced HSPCs generated 5-fold fewer myeloid and 3-fold fewer erythroid colonies. Additionally, Hu et al. demonstrated that the homeobox protein, HOXA9, regulated MIR155HG expression in myeloid cells and that this miRNA played a functional role in hematopoiesis. These investigators found that forced expression of miR-155-5p in bone marrow cells resulted in a ~50% decrease in SPI1 (i.e. PU.1), a transcription factor and a regulator of myelopoiesis, and a validated target of this miRNA. It was also established that in vitro differentiation of purified human erythroid progenitor cells resulted in a progressive decrease of miR-155-5p expression in mature red cells. Additionally, mice deficient in pre-mir-155 showed clear defects in lymphocyte development and generation of B- and T-cell responses in vivo. Finally, it was established that regulatory T-cell (Tregs) development required miR-155-5p and this miRNA was shown to play a role in Treg homeostasis and overall survival by directly targeting SOCS1, a negative regulator for IL-2 signaling. Taken together, these results strongly suggest that miR-155-5p is an essential molecule in the control of several aspects of hematopoiesis including myelopoiesis, erythropoiesis, and lymphopoiesis.
## Immune system
The innate immune system constitutes the first line of defense against invading pathogens and is regarded as the major initiator of inflammatory responses. Its cellular component involves primarily monocyte/macrophages, granulocytes, and dendritic cells (DCs), which are activated upon sensing of conserved pathogen structures (PAMPs) by pattern recognition receptors such as Toll-like receptors ((TLRs)). MIR155HG (i.e. miR-155-5p) expression is greatly enhanced by TLR agonist stimulation of macrophages and dendritic cells. Since microbial lipopolysaccharide (an agonist of TLR4) activates a chain of events that lead to the stimulation of the NF-κB and AP-1 transcription factors, it was hypothesized that endotoxin activation of MIR155HG may be mediated by those transcription factors. Indeed, MIR155HG expression was found to be activated in LPS treated murine macrophage cells (i.e. Raw264.7) by an NF-κB-mediated mechanism. Furthermore, H. pylori infection of primary murine bone marrow-derived macrophages resulted in a NF-κB dependent up-regulation of MIR155HG. In the context of viral infection vesicular stomatitis virus (VSV) challenge of murine peritoneal macrophages was reported to result in miR-155-5p over-expression via a retinoic acid-inducible gene I/JNK/NF-κB–dependent pathway. Support for a role of AP-1 in MIR155HG activation comes from studies using stimuli relevant to viral infection such as TLR3 ligand poly(I:C) or interferon beta (IFN-β). Downstream of those stimuli AP-1 seems to play a major role in MIR155HG activation.
Upon its initiation via activation of e.g. TLRs by pathogen stimuli miR-155-5p functions as a post-transcriptional regulator of innate immune signaling pathways. Importantly, miR-155-5p displays a similar responsivenes to pathogen stimuli (e.g. TLR4 agonist LPS) as major pro-inflammatory marker mRNAs. Once activated, miR-155-5p suppresses negative regulators of inflammation. These include inositol polyphosphate-5-phosphatase (INPP5D also denoted SHIP1) and suppressor of cytokine signaling 1 (SOCS1), suppression of which promotes cell survival, growth, migration, and anti-pathogen responses. Besides supporting the activation of defense pathways miR-155-5p may also limit the strength of the resulting NF-κB dependent inflammatory response, suggesting varying functions of miR-155 at different stages of inflammation.
Taken together, these observations imply that the activation of the MIR155HG may be context-dependent given that both AP-1- and NF-κB-mediated mechanisms regulate the expression of this gene. These studies also suggest that a broad range of viral and bacterial inflammatory mediators can stimulate the expression of miR-155-5p and indicate that there is an intimate relationship between inflammation, innate immunity and MIR155HG expression.
# Activity and phenotypes
There is evidence that miR-155 participates in cascades associated with cardiovascular diseases and hypertension, and was also found to be implicated in immunity, genomic instability, cell differentiation, inflammation, virus associated infections and cancer.
Protective roles of miR-155 may arise in response to its action on silencing genes thereby regulating their expression time, mutations in miR-155 target site deny it the optimal access necessary to bring about gene silencing, leading to over abundance of delinquent activities that may go malignant, for example, miR-155 role as a protective agent against predisposition to B Cell associated malignancies is emphasized by maintaining the balance of Activation-Induced Cytidine Deaminase (AID) enzyme. MiR-155 mediates regulation of AID abundance and expression time upon immunological cues however, mutations in the target on AID mRNA result in its unresponsiveness to miR-155 silencing and lead to unbridled expression of its protein causing wild immature B-lymphocyte surges and AID-mediated chromosomal translocations.
# Clinical significance
## Cardiovascular
Transfection of miR-155 into human primary lung fibroblasts reduces the endogenous expression of the angiotensin II receptor AT1R protein. Furthermore, AT1R mediates angiotensin II-related elevation in blood pressure and contributes to the pathogenesis of heart failure. Defective miR-155 function could be implicated in hypertension and cardiovascular diseases if the cis-regulatory site on 3` UTR of AT1R (miR-155 target site) was affected due to a SNP polymorphism in AT1R itself. This mutation is disruptive of miR-155 targeting and thus preventive of AT1R expression down-regulation. In low blood pressure over-expression of miR-155 correlates with the impairment of AT1R activity.
## Immunity
miR-155 is involved in immunity by playing key roles in modulating humoral and innate cell-mediated immune responses, for example, In miR-155 deficient mice, immunological-memory is impaired; making it fall prey to repetitive bouts of invasions by the same pathogen (Rodriguez et al. 2007), maturation and specificity of miR-155-deficient B-lymphocytes are impaired since the process relies on AID enzyme which has a miR-155 target in its 3' UTR end. The phenotypic consequences involving deficiency of miR-155 in mice show later in life where the animals develop lung and intestinal lesions.
Activated B and T cells show increased miR-155 expression, the same goes for macrophages and dendritic cells of the immune system. MiR-155 is crucial for proper lymphocyte development and maturation. Details of various manifestations of miR-155 levels and involvement in activities that ascertain optimal immune responses have been the subject of many researches:
### Reduction of IgG1
Defective T and B cells as well as markedly decreased IgG1 responses were observed in miR-155-deficient mice, IgG1 is reduced whereas the expression of the IgM immunoglobulin remains normal in these mice. The change in IgG1 levels maybe explained by the fact that it is a target for miR-155 in B cells, the protein-encoding mRNA for the transcriptional regulator Pu.1-protein, elevation of Pu.1 protein predisposes defective IgG1 production. In addition to Pu.1, there are nearly 60 other differentially elevated genes in miR-155 deficient B cells, further inspection revealed possible miR-155 target sites in the 3' UTR regions in these genes.
### Lymphocyte malignancies
Mature receptors affinity and specificity of lymphocytes to pathogenic agents underlie proper immune responses, optimal miR-155 coordination is required for manufacturing of normal B lymphocytes, production of high-affinity antibodies and balancing of BCR signalling. It has been demonstrated that miR-155 can be transferred through gap junctions from leukemic cells to healthy B cells and promote their transformation to tumorigenic-like cells
Selection of competent B cells takes place in the germinal center where they are trained to differentiate body cells vs. foreign antigens, they compete for antigen recognition and for T cell help, in this fashion of selective pressure those B Cells that demonstrated high-affinity receptors and cooperation with T cells (affinity maturation) are recruited and deployed to the bone marrow or become memory B cells, apoptotic termination takes place for those B Cells failing the competition. Immature B cells which are miR-155 deficient evade apoptosis as a result of elevated Bcl-2 protein levels; a protein that was found to be involved in B Cell malignancies and to be controlled by miR-155.
## Inflammation
Inflammatory responses to triggers such as TNF-α involve macrophages with components that include miR-155. miR-155 is overexpressed in atopic dermatitis and contributes to chronic skin inflammation by increasing the proliferative response of T(H) cells through the downregulation of CTLA-4. In Autoimmune disorders such as rheumatoid arthritis, miR-155 showed higher expression in patients' tissues and synovial fibroblasts. In multiple sclerosis, increased expression of mir-155 has also been measured in peripheral and CNS-resident myeloid cells, including circulating blood monocytes and activated microglia. It was also found that mir-155 is implicated in inflammation. Overexpression of mir-155 will lead to chronic inflammatory state in human.
## DNA viruses
In DNA viruses, miRNAs were experimentally verified, miRNAs in viruses are encoded by dsDNAs, examples of such viruses include herpesviruses such as Humans-Epstein-Barr Virus (EBV) and adenoviruses, another virus expressing miR-155-like miRNA in chickens is the oncogenic MDV-1 whose non-oncogenic relative MDV-2 does not, this suggests implication of miR-155 in lymphomagenesis.
Viruses can exploit host miRNAs to the degree that they use host miRNAs to encode for viral clones for example:
miR-K12-11 in Kaposi's-sarcoma-associated Herpesvirus has a target specificity region orthologous to that of miR-155's; mimicking the action of miR-155 and, sharing targets with it, thus it can be thought to suppress miR-155 accessibility to its targets by competition and this in effect downregulates expression of genes playing roles in cellular growth and apoptosis in a manner that defies regulations by miR-155.
EBV modulates host miR-155 expression, which is essential for growth of EBV-infected B cells. EBV-infected cells have increased expression of miR-155 thereby disturbing equilibrium of expression for genes regulating transcription in those cells.
## Cancer
Over-silencing by miR-155 may result in triggering oncogenic cascades that begin by apoptotic resistance, the pro-apoptotic Tumour Protein-53-induced-nuclear-protein1 (TP53INP1) is silenced by miR-155, over-expression of miR-155 leads to decreased levels of TP53INP1 in pancreatic ductal adenocarcinomas and possibly in other epithelial cancers where TP53INP1 activity is lost thereby resulting in apoptosis evasion and uncontrolled bouts of growth.
Inactivation of DNA Mismatch Repair (MMR) as identified by elevation of mutation rates is the cause of Lynch Syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), down-regulation of MMR controlling protein is carried out by over-expression of miR-155, MMR is controlled by a group of conserved proteins, reduced activity of these proteins results in elevated levels of mutations in the phenotype triggering a march towards developing this type of cancer.
Other types of tumors in which miR-155 over-expression was reported include: thyroid carcinoma, breast cancer, colon cancer, cervical cancer, and lung cancer, where distinct miR-155 expression profiles quantification can potentially serve as signals for tumor detection and evaluation of prognosis outcome. It is shown in an analysis that miR-155 expression is associated with survival in triple negative breast cancer.
# Notes | miR-155
MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG.[1] MiR-155 plays a role in various physiological and pathological processes.[2][3][4][5][6][7] Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth,[8][9] viral infections,[10] and enhance the progression of cardiovascular diseases.[11]
# Discovery
The MIR155HG was initially identified as a gene that was transcriptionally activated by promoter insertion at a common retroviral integration site in B-cell lymphomas and was formerly called BIC (B-cell Integration Cluster). The MIR155HG is transcribed by RNA polymerase II and the resulting ~1,500 nucleotide RNA is capped and polyadenylated. The 23 nucleotide single-stranded miR-155, which is harbored in exon 3, is subsequently processed from the parent RNA molecule.[12]
# Biogenesis
The MIR155HG RNA transcript does not contain a long open reading frame (ORF), however, it does include an imperfectly base-paired stem loop that is conserved across species.[13] This non-coding RNA (ncRNA) is now defined as a primary-miRNA (pri-miRNA).[13] Once miR-155 pri-miRNA is transcribed, this transcript is cleaved by the nuclear microprocessor complex, of which the core components are the RNase III type endonuclease Drosha and the DiGeorge critical region 8 (DGCR8) protein,[14][15] to produce a 65 nucleotide stem-loop precursor miRNA (pre-mir-155) (see Figure 2).
Following export from the nucleus by exportin-5, pre-mir-155 molecules are cleaved near the terminal loop by Dicer resulting in RNA duplexes of ~22nucleotides.[14][15] Following Dicer cleavage, an Argonaute (Ago) protein binds to the short RNA duplexes, forming the core of a multi-subunit complex called the RNA-induced silencing complex (RISC).[16] In a manner similar to siRNA duplexes, one of the two strands, the "passenger miRNA" (miR-155*), is released and degraded while the other strand, designated the "guide strand" or "mature miRNA" (miR-155), is retained within the RISC.[16]
Recent data suggest that both arms of the pre-miRNA hairpin can give rise to mature miRNAs.[17][18] Due to the increasing number of examples where two functional mature miRNAs are processed from opposite arms of the same pre-miRNA, pre-mir-155 products are now denoted with the suffix -5p (from the 5′ arm) (e.g. miR-155-5p) and -3p (from the 3′ arm) (e.g. miR-155-3p) following their name (see Figure 3).[19]
Once miR-155-5p/-3p is assembled into the RISC, these molecules subsequently recognize their target messenger RNA (mRNA) by base pairing interactions between nucleotides 2 and 8 of miR-155-5p/-3p (the seed region) and complementary nucleotides predominantly in the 3'-untranslated region (3'-UTR) of mRNAs (see Figure 4 and 5 below).[20] Finally, with the miR-155-5p/-3p acting as an adaptor for the RISC, complex-bound mRNAs are subjected to translational repression (i.e. inhibition of translation initiation) and/or degradation following deadenylation.[16]
# Evolutionary conservation
Early phylogenetic analyses demonstrated that the sequence of pre-mir-155 and miR-155-5p was conserved between human, mouse, and chicken.[13] Recent annotated sequencing data found that 22 different organisms including, mammals, amphibians, birds, reptiles, sea squirts, and sea lampreys, express a conserved miR-155-5p.[2] Currently much less sequence data is available regarding miR-155-3p, therefore, it is not clear how conserved this miRNA is across species.[3]
# Tissue distribution
Northern blot analysis found that miR-155 pri-miRNA was abundantly expressed in the human spleen and thymus and detectable in the liver, lung, and kidney.[13] Subsequently, polymerase chain reaction (PCR) experiments demonstrated that miR-155-5p was detectable in all human tissues investigated.[21] Sequence analysis of small RNA clone libraries comparing miRNA expression to all other organ systems examined established that miR-155-5p was one of five miRNAs (i.e. miR-142, miR-144, miR-150, miR-155, and miR-223) that was specific for hematopoietic cells including B-cells, T-cells, monocytes and granulocytes.[22] Together these results suggest that miR-155-5p is expressed in a number of tissues and cell types and, therefore, may play a critical role in a wide variety of biological processes, including hematopoiesis [2][3][4]
Although very few studies have investigated the expression levels of miR-155-3p, Landgraf et al.[22] established that expression levels of this miRNA was very low in hematopoietic cells. Additionally, PCR analyses found that while miR-155-3p was detectable in a number of human tissues the expression levels of this miRNA were 20-200 fold less when compared to miR-155-5p levels.[23] Even though the function of miR-155-3p has been largely ignored, several studies now suggest that, in some cases (astrocytes and plasmacytoid dendritic cells), both miR-155-5p and -3p can be functionally matured from pre-mir-155.[24][25]
# Targets
Bioinformatic analysis using TargetScan 6.2 (release date June, 2012) [4] revealed at least 4,174 putative human miR-155-5p mRNA targets exist, with a total of 918 conserved sites (i.e. between mouse and human) and 4,249 poorly conserved sites (i.e. human only).[20][26] Although the TargetScan 6.2 algorithm cannot be utilized to determine the miR-155-3p putative targets, one would speculate that this miRNA may also potentially regulate the expression of thousands of mRNA targets.
A comprehensive list of miR-155-5p/mRNA targets that were experimentally authenticated by both the demonstration of endogenous transcript regulation by miR-155-5p and validation of the miR-155-5p seed sequence through a reporter assay was recently assembled.[27] This list included 140 genes and included regulatory proteins for myelopoiesis and leukemogenesis (e.g. SHIP-1, AICDA, ETS1, JARID2, SPI1, etc.), inflammation (e.g. BACH1, FADD, IKBKE, INPP5D, MYD88, RIPK1, SPI1, SOCS, etc.) and known tumor suppressors (e.g. CEBPβ, IL17RB, PCCD4, TCF12, ZNF652, etc.).[27] The validated miR-155-5p binding site harbored in the SPI1 mRNA[28] and the validated miR-155-3p binding site harbored in the IRAK3 mRNA [25] are shown in Figures 4 and 5 respectively.
# Physiological roles
## Hematopoiesis
Hematopoiesis is defined as the formation and development of blood cells, all of which are derived from hematopoietic stem-progenitor cells (HSPCs).[29] HSPCs are primitive cells capable of self-renewal and initially differentiate into common myeloid progenitor (CMP) or common lymphoid progenitor (CLP) cells.[29] CMPs represent the cellular population that has become myeloid lineage and it is the point that myelopoeisis begins.[29] During myelopoeisis further cellular differentiation takes place including thrombopoiesis, erythropoeisis, granulopoeisis, and monocytopoeisis.[29] CLPs subsequently differentiate into B-cells and T-cells in a process designated lymphopoiesis.[29] Given that miR-155-5p is expressed in hematopoietic cells[22] it was hypothesized that this miRNA plays a critical role in these cellular differentiation processes. In support of this premise, miR-155-5p was found to be expressed in CD34(+) human HSPCs, and it was speculated that this miRNA may hold these cells at an early stem-progenitor stage, inhibiting their differentiation into a more mature cell (i.e. megakaryocytic/erythroid/granulocytic/monocytic/B-lymphoid/T-lymphoid).[30] This hypothesis was substantiated when pre-mir-155 transduced HSPCs generated 5-fold fewer myeloid and 3-fold fewer erythroid colonies.[30] Additionally, Hu et al.[31] demonstrated that the homeobox protein, HOXA9, regulated MIR155HG expression in myeloid cells and that this miRNA played a functional role in hematopoiesis. These investigators found that forced expression of miR-155-5p in bone marrow cells resulted in a ~50% decrease in SPI1 (i.e. PU.1),[31] a transcription factor and a regulator of myelopoiesis,[32] and a validated target of this miRNA.[28] It was also established that in vitro differentiation of purified human erythroid progenitor cells resulted in a progressive decrease of miR-155-5p expression in mature red cells.[33] Additionally, mice deficient in pre-mir-155 showed clear defects in lymphocyte development and generation of B- and T-cell responses in vivo.[28][34][35] Finally, it was established that regulatory T-cell (Tregs) development required miR-155-5p and this miRNA was shown to play a role in Treg homeostasis and overall survival by directly targeting SOCS1, a negative regulator for IL-2 signaling.[36][37] Taken together, these results strongly suggest that miR-155-5p is an essential molecule in the control of several aspects of hematopoiesis including myelopoiesis, erythropoiesis, and lymphopoiesis.
## Immune system
The innate immune system constitutes the first line of defense against invading pathogens and is regarded as the major initiator of inflammatory responses.[38] Its cellular component involves primarily monocyte/macrophages, granulocytes, and dendritic cells (DCs), which are activated upon sensing of conserved pathogen structures (PAMPs) by pattern recognition receptors such as Toll-like receptors ((TLRs)).[39] MIR155HG (i.e. miR-155-5p) expression is greatly enhanced by TLR agonist stimulation of macrophages and dendritic cells.[40][41][42][43][44][45] Since microbial lipopolysaccharide (an agonist of TLR4) activates a chain of events that lead to the stimulation of the NF-κB and AP-1 transcription factors,[39] it was hypothesized that endotoxin activation of MIR155HG may be mediated by those transcription factors.[40] Indeed, MIR155HG expression was found to be activated in LPS treated murine macrophage cells (i.e. Raw264.7) by an NF-κB-mediated mechanism.[41] Furthermore, H. pylori infection of primary murine bone marrow-derived macrophages resulted in a NF-κB dependent up-regulation of MIR155HG.[46] In the context of viral infection vesicular stomatitis virus (VSV) challenge of murine peritoneal macrophages was reported to result in miR-155-5p over-expression via a retinoic acid-inducible gene I/JNK/NF-κB–dependent pathway.[47] Support for a role of AP-1 in MIR155HG activation comes from studies using stimuli relevant to viral infection such as TLR3 ligand poly(I:C) or interferon beta (IFN-β).[42] Downstream of those stimuli AP-1 seems to play a major role in MIR155HG activation.[42][48][49][50]
Upon its initiation via activation of e.g. TLRs by pathogen stimuli miR-155-5p functions as a post-transcriptional regulator of innate immune signaling pathways. Importantly, miR-155-5p displays a similar responsivenes to pathogen stimuli (e.g. TLR4 agonist LPS) as major pro-inflammatory marker mRNAs.[51] Once activated, miR-155-5p suppresses negative regulators of inflammation. These include inositol polyphosphate-5-phosphatase (INPP5D also denoted SHIP1) and suppressor of cytokine signaling 1 (SOCS1), suppression of which promotes cell survival, growth, migration, and anti-pathogen responses.[47][52][53][54] Besides supporting the activation of defense pathways miR-155-5p may also limit the strength of the resulting NF-κB dependent inflammatory response,[51] suggesting varying functions of miR-155 at different stages of inflammation.
Taken together, these observations imply that the activation of the MIR155HG may be context-dependent given that both AP-1- and NF-κB-mediated mechanisms regulate the expression of this gene. These studies also suggest that a broad range of viral and bacterial inflammatory mediators can stimulate the expression of miR-155-5p and indicate that there is an intimate relationship between inflammation, innate immunity and MIR155HG expression.
# Activity and phenotypes
There is evidence that miR-155 participates in cascades associated with cardiovascular diseases and hypertension, and was also found to be implicated in immunity, genomic instability, cell differentiation, inflammation, virus associated infections and cancer.[citation needed]
Protective roles of miR-155 may arise in response to its action on silencing genes thereby regulating their expression time, mutations in miR-155 target site deny it the optimal access necessary to bring about gene silencing, leading to over abundance of delinquent activities that may go malignant, for example, miR-155 role as a protective agent against predisposition to B Cell associated malignancies is emphasized by maintaining the balance of Activation-Induced Cytidine Deaminase (AID) enzyme. MiR-155 mediates regulation of AID abundance and expression time upon immunological cues however, mutations in the target on AID mRNA result in its unresponsiveness to miR-155 silencing and lead to unbridled expression of its protein causing wild immature B-lymphocyte surges and AID-mediated chromosomal translocations.[3][4]
# Clinical significance
## Cardiovascular
Transfection of miR-155 into human primary lung fibroblasts reduces the endogenous expression of the angiotensin II receptor AT1R protein. Furthermore, AT1R mediates angiotensin II-related elevation in blood pressure and contributes to the pathogenesis of heart failure. Defective miR-155 function could be implicated in hypertension and cardiovascular diseases if the cis-regulatory site on 3` UTR of AT1R (miR-155 target site) was affected due to a SNP polymorphism in AT1R itself. This mutation is disruptive of miR-155 targeting and thus preventive of AT1R expression down-regulation.[3] In low blood pressure over-expression of miR-155 correlates with the impairment of AT1R activity.[2]
## Immunity
miR-155 is involved in immunity by playing key roles in modulating humoral and innate cell-mediated immune responses, for example, In miR-155 deficient mice, immunological-memory is impaired; making it fall prey to repetitive bouts of invasions by the same pathogen (Rodriguez et al. 2007), maturation and specificity of miR-155-deficient B-lymphocytes are impaired since the process relies on AID enzyme which has a miR-155 target in its 3' UTR end.[3][4] The phenotypic consequences involving deficiency of miR-155 in mice show later in life where the animals develop lung and intestinal lesions.[2]
Activated B and T cells show increased miR-155 expression, the same goes for macrophages and dendritic cells of the immune system. MiR-155 is crucial for proper lymphocyte development and maturation. Details of various manifestations of miR-155 levels and involvement in activities that ascertain optimal immune responses have been the subject of many researches:
### Reduction of IgG1
Defective T and B cells as well as markedly decreased IgG1 responses were observed in miR-155-deficient mice, IgG1 is reduced whereas the expression of the IgM immunoglobulin remains normal in these mice. The change in IgG1 levels maybe explained by the fact that it is a target for miR-155 in B cells, the protein-encoding mRNA for the transcriptional regulator Pu.1-protein, elevation of Pu.1 protein predisposes defective IgG1 production. In addition to Pu.1, there are nearly 60 other differentially elevated genes in miR-155 deficient B cells, further inspection revealed possible miR-155 target sites in the 3' UTR regions in these genes.[4]
### Lymphocyte malignancies
Mature receptors affinity and specificity of lymphocytes to pathogenic agents underlie proper immune responses, optimal miR-155 coordination is required for manufacturing of normal B lymphocytes, production of high-affinity antibodies and balancing of BCR signalling. It has been demonstrated that miR-155 can be transferred through gap junctions from leukemic cells to healthy B cells and promote their transformation to tumorigenic-like cells [55]
Selection of competent B cells takes place in the germinal center where they are trained to differentiate body cells vs. foreign antigens, they compete for antigen recognition and for T cell help, in this fashion of selective pressure those B Cells that demonstrated high-affinity receptors and cooperation with T cells (affinity maturation) are recruited and deployed to the bone marrow or become memory B cells, apoptotic termination takes place for those B Cells failing the competition. Immature B cells which are miR-155 deficient evade apoptosis as a result of elevated Bcl-2 protein levels; a protein that was found to be involved in B Cell malignancies and to be controlled by miR-155.[4]
## Inflammation
Inflammatory responses to triggers such as TNF-α involve macrophages with components that include miR-155. miR-155 is overexpressed in atopic dermatitis and contributes to chronic skin inflammation by increasing the proliferative response of T(H) cells through the downregulation of CTLA-4.[56] In Autoimmune disorders such as rheumatoid arthritis, miR-155 showed higher expression in patients' tissues and synovial fibroblasts.[2] In multiple sclerosis, increased expression of mir-155 has also been measured in peripheral and CNS-resident myeloid cells, including circulating blood monocytes and activated microglia.[57] It was also found that mir-155 is implicated in inflammation. Overexpression of mir-155 will lead to chronic inflammatory state in human.[58]
## DNA viruses
In DNA viruses, miRNAs were experimentally verified, miRNAs in viruses are encoded by dsDNAs,[3] examples of such viruses include herpesviruses such as Humans-Epstein-Barr Virus (EBV) and adenoviruses,[2] another virus expressing miR-155-like miRNA in chickens is the oncogenic MDV-1 whose non-oncogenic relative MDV-2 does not, this suggests implication of miR-155 in lymphomagenesis.[3]
Viruses can exploit host miRNAs to the degree that they use host miRNAs to encode for viral clones for example:
miR-K12-11 in Kaposi's-sarcoma-associated Herpesvirus has a target specificity region orthologous to that of miR-155's; mimicking the action of miR-155 [59] and, sharing targets with it, thus it can be thought to suppress miR-155 accessibility to its targets by competition and this in effect downregulates expression of genes playing roles in cellular growth and apoptosis in a manner that defies regulations by miR-155.[2]
EBV modulates host miR-155 expression, which is essential for growth of EBV-infected B cells.[60] EBV-infected cells have increased expression of miR-155 thereby disturbing equilibrium of expression for genes regulating transcription in those cells.[2][3]
## Cancer
Over-silencing by miR-155 may result in triggering oncogenic cascades that begin by apoptotic resistance, the pro-apoptotic Tumour Protein-53-induced-nuclear-protein1 (TP53INP1) is silenced by miR-155, over-expression of miR-155 leads to decreased levels of TP53INP1 in pancreatic ductal adenocarcinomas and possibly in other epithelial cancers where TP53INP1 activity is lost thereby resulting in apoptosis evasion and uncontrolled bouts of growth.[3]
Inactivation of DNA Mismatch Repair (MMR) as identified by elevation of mutation rates is the cause of Lynch Syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), down-regulation of MMR controlling protein is carried out by over-expression of miR-155, MMR is controlled by a group of conserved proteins, reduced activity of these proteins results in elevated levels of mutations in the phenotype triggering a march towards developing this type of cancer.[61]
Other types of tumors in which miR-155 over-expression was reported include: thyroid carcinoma, breast cancer, colon cancer, cervical cancer, and lung cancer, where distinct miR-155 expression profiles quantification can potentially serve as signals for tumor detection and evaluation of prognosis outcome.[2] It is shown in an analysis that miR-155 expression is associated with survival in triple negative breast cancer.[62]
# Notes | https://www.wikidoc.org/index.php/MiR-155 | |
eda5ae11b86f74f2c19109e73f19bba6ea5d5ad8 | wikidoc | miR-191 | miR-191
miR-191 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
miR-191 has been found to be dysregulated in a large number of different types of human tumour, including those of colorectal, breast and prostate cancers. Despite these cancer links, target genes of the mature miRNA have not been characterised, and it is not known which factors lead to its dysregulation in certain tumour cells.
The expression profile of miR-191 could be implemented in prognosis of acute myeloid leukaemia, with higher than average levels of miR-191 suggesting a lower survival probability. | miR-191
miR-191 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
miR-191 has been found to be dysregulated in a large number of different types of human tumour, including those of colorectal,[3] breast and prostate cancers.[4] Despite these cancer links, target genes of the mature miRNA have not been characterised, and it is not known which factors lead to its dysregulation in certain tumour cells.[5]
The expression profile of miR-191 could be implemented in prognosis of acute myeloid leukaemia, with higher than average levels of miR-191 suggesting a lower survival probability.[6] | https://www.wikidoc.org/index.php/MiR-191 | |
af885e05d85058eb28d328ae66e8642b218e5ece | wikidoc | miR-208 | miR-208
miR-208 is a family of microRNA precursors found in animals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
In humans, the gene for miR-208 is located in an intron of MYH7.
# Function
miR-208 has been deemed a "myomiR" as it is specifically expressed, or found at much higher levels, in cardiac tissue. Other myomiRs include miR-1 and miR-133. miR-208 is thought to be dysregulated in various cardiovascular diseases.
miR-208 functions in cardiomyocytes regulating the production of the myosin heavy chain during development. It also responds to stress and forms part of a hormonal signalling cascade in cardiac cells.
# Applications
A preliminary study has shown a potential use in the prognosis of dilated cardiomyopathy. Another application has been suggested as using plasma concentration of miR-208 as a biomarker of damaged cardiac muscle cells. | miR-208
miR-208 is a family of microRNA precursors found in animals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
In humans, the gene for miR-208 is located in an intron of MYH7.[3]
# Function
miR-208 has been deemed a "myomiR"[3] as it is specifically expressed, or found at much higher levels, in cardiac tissue. Other myomiRs include miR-1 and miR-133.[3] miR-208 is thought to be dysregulated in various cardiovascular diseases.[4][5]
miR-208 functions in cardiomyocytes regulating the production of the myosin heavy chain during development.[3] It also responds to stress and forms part of a hormonal signalling cascade in cardiac cells.[6]
# Applications
A preliminary study has shown a potential use in the prognosis of dilated cardiomyopathy.[7] Another application has been suggested as using plasma concentration of miR-208 as a biomarker of damaged cardiac muscle cells.[8] | https://www.wikidoc.org/index.php/MiR-208 | |
cdf3667c6c02aa3043217717c7c564c74ce460c8 | wikidoc | miR-214 | miR-214
miR-214 is a vertebrate-specific family of microRNA precursors. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
# Origin and evolution of miR-214
miR-214 is a vertebrate-specific miR family that possesses one member in non-teleost vertebrates and two members in teleost fish. miR-214 is likely to have emerged within the Dnm3 gene after the divergence of jawed and jawless vertebrates and is located on the opposite strand of an intron of Dnm3 and is associated in an expression cluster with miR-199.
# Function
miR-214 is a "melano-miR", so-called because it is thought to encourage the metastasis of melanoma. Specifically, the mature microRNA excised from miR-214 is predicted to target two activating protein 2 transcription factors, bringing about downstream effects on a number of genes regulating vital cell cycle processes, such as apoptosis, proliferation and angiogenesis.
miR-214 is also thought to regulate type-I collagen.
# Role in cancer
miR-214 has been found to be downregulated in human cervical cancer; when miR-214 was upregulated in HeLa cancer cells, it was found to significantly reduce cell growth. Two mRNA targets were identified as those encoding the proteins MAP2K3 and MAPK8.
The increased expression of miR-214 in pancreatic cancer could bring about increased resistance to chemotherapy.
In human glioma cell line T98G expression of miR-214 has been shown to suppress expression of the ubiquitin-conjugating enzyme 9 (UBC9) and reduces tumour cell proliferation. The protein UBC9 is involved in the sumoylation pathway, and is up-regulated in many cancers.
# Implication of miR-214 in skeletogenesis
miR-214, along with its cluster mate miR-199, has been shown to be implicated in skeleton formation. miR-214 has been shown to inhibit bone formation in human cell lines both by targeting ATF4, a gene encoding one of the maintranscription factors required for osteoblast function and by suppressing osteogenic differentiation of C2C12 myoblast cells by targeting Sp7, an osteoblast-specific transcription factor. Also, Twist-1, which is a major actor in skeleton formation, regulates miR-199 and miR-214 cluster expression in mouse. Furthermore, miR199-214 cluster deletion in mouse lead to skeletal development abnormalities including craniofacial defects, neural arch and spinous processes malformations, and osteopenia. In zebrafish, miR-214 expression is mainly observed around developing skeletal elements. | miR-214
miR-214 is a vertebrate-specific family of microRNA precursors. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
# Origin and evolution of miR-214
miR-214 is a vertebrate-specific miR family that possesses one member in non-teleost vertebrates and two members in teleost fish. miR-214 is likely to have emerged within the Dnm3 gene after the divergence of jawed and jawless vertebrates and is located on the opposite strand of an intron of Dnm3 and is associated in an expression cluster with miR-199.[3]
# Function
miR-214 is a "melano-miR",[4] so-called because it is thought to encourage the metastasis of melanoma. Specifically, the mature microRNA excised from miR-214 is predicted to target two activating protein 2 transcription factors, bringing about downstream effects on a number of genes regulating vital cell cycle processes, such as apoptosis, proliferation and angiogenesis.[4]
miR-214 is also thought to regulate type-I collagen.[5]
# Role in cancer
miR-214 has been found to be downregulated in human cervical cancer; when miR-214 was upregulated in HeLa cancer cells, it was found to significantly reduce cell growth.[6] Two mRNA targets were identified as those encoding the proteins MAP2K3 and MAPK8.[6]
The increased expression of miR-214 in pancreatic cancer could bring about increased resistance to chemotherapy.[7]
In human glioma cell line T98G expression of miR-214 has been shown to suppress expression of the ubiquitin-conjugating enzyme 9 (UBC9) and reduces tumour cell proliferation. The protein UBC9 is involved in the sumoylation pathway, and is up-regulated in many cancers.[8]
# Implication of miR-214 in skeletogenesis
miR-214, along with its cluster mate miR-199, has been shown to be implicated in skeleton formation. miR-214 has been shown to inhibit bone formation in human cell lines both by targeting ATF4,[9] a gene encoding one of the maintranscription factors required for osteoblast function and by suppressing osteogenic differentiation of C2C12 myoblast cells by targeting Sp7,[10] an osteoblast-specific transcription factor. Also, Twist-1, which is a major actor in skeleton formation, regulates miR-199 and miR-214 cluster expression in mouse.[11] Furthermore, miR199-214 cluster deletion in mouse lead to skeletal development abnormalities including craniofacial defects, neural arch and spinous processes malformations, and osteopenia.[12] In zebrafish, miR-214 expression is mainly observed around developing skeletal elements.[3] | https://www.wikidoc.org/index.php/MiR-214 | |
77036d6d714e14da171a839167ab00aa15d72ccf | wikidoc | miR-224 | miR-224
miR-224 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.
# Function
miR-224, being located on the X-chromosome, is thought to be active in mammalian ovaries, and possibly responds to TGF beta 1. A target of miR-224 has been predicted to be SMAD4. Experimental evidence has shown that while the SMAD4 mRNA level is unchanged, increased miR-224 expression decreases concentration of SMDA4 protein in murine granulosa cells. This is consistent with post-transcriptional miRNA regulation.
# Role in cancer
miR-224 has been noted as the most upregulated microRNA in hepatocellular carcinoma. The same study identified a target of mir-224 as apoptosis-inhibitor 5 (API-5).
miR-224 has also been linked with pancreatic ductal carcinoma, where it is thought to repress CD40 expression in cancer cells. | miR-224
miR-224 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1]
# Function
miR-224, being located on the X-chromosome, is thought to be active in mammalian ovaries, and possibly responds to TGF beta 1.[2] A target of miR-224 has been predicted to be SMAD4. Experimental evidence has shown that while the SMAD4 mRNA level is unchanged, increased miR-224 expression decreases concentration of SMDA4 protein in murine granulosa cells.[3] This is consistent with post-transcriptional miRNA regulation.[2]
# Role in cancer
miR-224 has been noted as the most upregulated microRNA in hepatocellular carcinoma.[4] The same study identified a target of mir-224 as apoptosis-inhibitor 5 (API-5).[4]
miR-224 has also been linked with pancreatic ductal carcinoma, where it is thought to repress CD40 expression in cancer cells.[5] | https://www.wikidoc.org/index.php/MiR-224 | |
d065cf4bc5e507c07e8e0bdcdc8d3b62f191bce1 | wikidoc | miR-296 | miR-296
miR-296 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
miR-296 has been named an "angiomiR" due to being characterised as a microRNA which regulates angiogenesis, the process of growth and creation of new blood vessels. miR-296 is thought to have a specific role in cancer in promoting tumour angiogenesis. It achieves this by targeting HGS mRNA, reducing its expression in endothelial cells which then results in greater number of VEGF receptors.
miR-296 has predicted target sites in the transcription factor NANOG and may also contribute to carcinogenesis by dysregulating p53. | miR-296
miR-296 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[1] This sequence then associates with RISC which effects RNA interference.[2]
miR-296 has been named an "angiomiR"[3] due to being characterised as a microRNA which regulates angiogenesis, the process of growth and creation of new blood vessels.[4] miR-296 is thought to have a specific role in cancer in promoting tumour angiogenesis.[3][5] It achieves this by targeting HGS mRNA, reducing its expression in endothelial cells which then results in greater number of VEGF receptors.[3][6]
miR-296 has predicted target sites in the transcription factor NANOG[7] and may also contribute to carcinogenesis by dysregulating p53.[8] | https://www.wikidoc.org/index.php/MiR-296 | |
62cefa18f5e7c236aae0d95fc2d32dfefa2a10a7 | wikidoc | miR-338 | miR-338
miR-338 is a family of brain-specific microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.
miR-338 is located in an intronic region within the gene for apoptosis-associated tyrosine kinase (AATK). It has been predicted that it may downregulate genes which have a downstream negative effect on AATK expression.
# Function
miR-338 is a brain-specific miRNA which regulates the expression of cytochrome c oxidase IV (COX4). The mature miR-338 miRNA sequence is complementary to a short section of the 3' untranslated region of COX4 mRNA. This mRNA sequence is presented atop a stem-loop structure, indicating it is accessible to miRNA processing.
# Applications
miR-338 is dysregulated in neuroblastoma, and could potentially be implemented as a biomarker or future therapeutic agent. miR-338 has also been linked with hepatocellular carcinoma, and a large-scale diagnostic test has been suggested involving measurement of miR-338 expression in tissue samples. Furthermore, miR-338 is one of seven microRNAs whose expression profiles can be combined to give a prediction of the probability of survival of a patient with gastric cancer. | miR-338
miR-338 is a family of brain-specific microRNA precursors found in mammals, including humans.[1] The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer.[2] This sequence then associates with RISC which effects RNA interference.[3]
miR-338 is located in an intronic region within the gene for apoptosis-associated tyrosine kinase (AATK). It has been predicted that it may downregulate genes which have a downstream negative effect on AATK expression.[4]
# Function
miR-338 is a brain-specific miRNA which regulates the expression of cytochrome c oxidase IV (COX4).[1][5] The mature miR-338 miRNA sequence is complementary to a short section of the 3' untranslated region of COX4 mRNA. This mRNA sequence is presented atop a stem-loop structure, indicating it is accessible to miRNA processing.[5]
# Applications
miR-338 is dysregulated in neuroblastoma, and could potentially be implemented as a biomarker or future therapeutic agent.[6] miR-338 has also been linked with hepatocellular carcinoma, and a large-scale diagnostic test has been suggested involving measurement of miR-338 expression in tissue samples.[7] Furthermore, miR-338 is one of seven microRNAs whose expression profiles can be combined to give a prediction of the probability of survival of a patient with gastric cancer.[8] | https://www.wikidoc.org/index.php/MiR-338 | |
9b4df898351f270fffbeed98b554b611c8966520 | wikidoc | Micelle | Micelle
A micelle (rarely micella, plural micellae) is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre. This type of micelle is known as a normal phase micelle (oil-in-water micelle). Inverse micelles have the headgroups at the centre with the tails extending out (water-in-oil micelle). Micelles are approximately spherical in shape. Other phases, including shapes such as ellipsoids, cylinders, and bilayers are also possible. The shape and size of a micelle is a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. The process of forming micellae is known as micellisation and forms part of the phase behaviour of many lipids according to their polymorphism.
# History
The ability of a soapy solution to act as a detergent has been recognised for centuries. However it was only at the beginning of the twentieth century that the constitution of such solutions was scientifically studied. Pioneering work in this area was carried out by James William McBain at the University of Bristol. As early as 1913 he postulated the existence of “colloidal ions” to explain the good electrolytic conductivity of sodium palmitate solutions.- These highly mobile, spontaneously formed clusters came to be called micelles, a term borrowed from biology and popularized by G.S. Hartley in his classic book “Paraffin Chain Salts, A Study in Micelle Formation”.*
# Solvation
Individual surfactant molecules that are in the system but are not part of a micelle are called "monomers." In water, the hydrophilic "heads" of surfactant molecules are always in contact with the solvent, regardless of whether the surfactants exist as monomers or as part of a micelle. However, the lipophilic "tails" of surfactant molecules have less contact with water when they are part of a micelle -- this being the basis for the energetic drive for micelle formation. In a micelle, the hydrophobic tails of several surfactant molecules assemble into an oil-like core the most stable form of which has no contact with water. By contrast, surfactant monomers are surrounded by water molecules that create a "cage" of molecules connected by hydrogen bonds. This water cage is similar to a clathrate and has an ice-like crystal structure.
Micelles composed of ionic surfactants have an electrostatic attraction to the ions that surround them in solution, the latter known as counterions. Although the closest counterions partially mask a charged micelle (by up to 90%), the effects of micelle charge affect the structure of the surrounding solvent at appreciable distances from the micelle. Ionic micelles influence many properties of the mixture, including its electrical conductivity. Adding salts to a colloid containing micelles can decrease the strength of electrostatic interactions and lead to the formation of larger ionic micelles. This is more accurately seen from the point of view of an effective change in hydration of the system.
# Energy of formation
Micelles only form when the concentration of surfactant is greater than the critical micelle concentration (CMC), and the temperature of the system is greater than the critical micelle temperature, or Krafft temperature. The formation of micelles can be understood using thermodynamics: micelles can form spontaneously because of a balance between entropy and enthalpy. In water, the hydrophobic effect is the driving force for micelle formation, despite the fact that assembling surfactant molecules together reduces their entropy. Broadly speaking, above the CMC, the entropic penalty of assembling the surfactant molecules is less than the entropic penalty of caging water molecules. Also important are enthalpic considerations, such as the electrostatic interactions that occur between the charged parts surfactants.
# Inverse Micelles
In a non-polar solvent, it is the exposure of the hydrophilic head groups to the surrounding solvent that is energetically unfavourable, giving rise to a water-in-oil system. In this case the hydrophilic groups are sequestered in the micelle core and the hydrophobic groups extend away from the centre. These inverse micelles are proportionally less likely to form on increasing headgroup charge, since hydrophilic sequestration would create highly unfavorable electrostatic interactions.
# Uses
When surfactants are present above the CMC (Critical micelle concentration), they can act as emulsifiers that will allow a compound normally insoluble (in the solvent being used) to dissolve. This occurs because the insoluble species can be incorporated into the micelle core, which is itself solubilized in the bulk solvent by virtue of the head groups' favorable interactions with solvent species. The most common example of this phenomenon is detergents, which clean poorly soluble lipophilic material (such as oils and waxes) that cannot be removed by water alone. Detergents also clean by lowering the surface tension of water, making it easier to remove material from a surface. The emulsifying property of surfactants is also the basis for emulsion polymerization.
Micelle formation is essential for the absorption of fat-soluble vitamins and complicated lipids within the human body. Bile salts formed in the liver and secreted by the gall bladder allow micelles of fatty acids to form. This allows the absorption of complicated lipids (e.g., lecithin) and lipid soluble vitamins (A, D, E and K) by the small intestine within the micelle. | Micelle
A micelle (rarely micella, plural micellae) is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre. This type of micelle is known as a normal phase micelle (oil-in-water micelle). Inverse micelles have the headgroups at the centre with the tails extending out (water-in-oil micelle). Micelles are approximately spherical in shape. Other phases, including shapes such as ellipsoids, cylinders, and bilayers are also possible. The shape and size of a micelle is a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. The process of forming micellae is known as micellisation and forms part of the phase behaviour of many lipids according to their polymorphism.
# History
The ability of a soapy solution to act as a detergent has been recognised for centuries. However it was only at the beginning of the twentieth century that the constitution of such solutions was scientifically studied. Pioneering work in this area was carried out by James William McBain at the University of Bristol. As early as 1913 he postulated the existence of “colloidal ions” to explain the good electrolytic conductivity of sodium palmitate solutions.* These highly mobile, spontaneously formed clusters came to be called micelles, a term borrowed from biology and popularized by G.S. Hartley in his classic book “Paraffin Chain Salts, A Study in Micelle Formation”.*
# Solvation
Individual surfactant molecules that are in the system but are not part of a micelle are called "monomers." In water, the hydrophilic "heads" of surfactant molecules are always in contact with the solvent, regardless of whether the surfactants exist as monomers or as part of a micelle. However, the lipophilic "tails" of surfactant molecules have less contact with water when they are part of a micelle -- this being the basis for the energetic drive for micelle formation. In a micelle, the hydrophobic tails of several surfactant molecules assemble into an oil-like core the most stable form of which has no contact with water. By contrast, surfactant monomers are surrounded by water molecules that create a "cage" of molecules connected by hydrogen bonds. This water cage is similar to a clathrate and has an ice-like crystal structure.
Micelles composed of ionic surfactants have an electrostatic attraction to the ions that surround them in solution, the latter known as counterions. Although the closest counterions partially mask a charged micelle (by up to 90%), the effects of micelle charge affect the structure of the surrounding solvent at appreciable distances from the micelle. Ionic micelles influence many properties of the mixture, including its electrical conductivity. Adding salts to a colloid containing micelles can decrease the strength of electrostatic interactions and lead to the formation of larger ionic micelles. This is more accurately seen from the point of view of an effective change in hydration of the system.
# Energy of formation
Micelles only form when the concentration of surfactant is greater than the critical micelle concentration (CMC), and the temperature of the system is greater than the critical micelle temperature, or Krafft temperature. The formation of micelles can be understood using thermodynamics: micelles can form spontaneously because of a balance between entropy and enthalpy. In water, the hydrophobic effect is the driving force for micelle formation, despite the fact that assembling surfactant molecules together reduces their entropy. Broadly speaking, above the CMC, the entropic penalty of assembling the surfactant molecules is less than the entropic penalty of caging water molecules. Also important are enthalpic considerations, such as the electrostatic interactions that occur between the charged parts surfactants.
# Inverse Micelles
In a non-polar solvent, it is the exposure of the hydrophilic head groups to the surrounding solvent that is energetically unfavourable, giving rise to a water-in-oil system. In this case the hydrophilic groups are sequestered in the micelle core and the hydrophobic groups extend away from the centre. These inverse micelles are proportionally less likely to form on increasing headgroup charge, since hydrophilic sequestration would create highly unfavorable electrostatic interactions.
# Uses
When surfactants are present above the CMC (Critical micelle concentration), they can act as emulsifiers that will allow a compound normally insoluble (in the solvent being used) to dissolve. This occurs because the insoluble species can be incorporated into the micelle core, which is itself solubilized in the bulk solvent by virtue of the head groups' favorable interactions with solvent species. The most common example of this phenomenon is detergents, which clean poorly soluble lipophilic material (such as oils and waxes) that cannot be removed by water alone. Detergents also clean by lowering the surface tension of water, making it easier to remove material from a surface. The emulsifying property of surfactants is also the basis for emulsion polymerization.
Micelle formation is essential for the absorption of fat-soluble vitamins and complicated lipids within the human body. Bile salts formed in the liver and secreted by the gall bladder allow micelles of fatty acids to form. This allows the absorption of complicated lipids (e.g., lecithin) and lipid soluble vitamins (A, D, E and K) by the small intestine within the micelle. | https://www.wikidoc.org/index.php/Micelle | |
c3070bb1d71c60c4b0ad9e95ddd214d848480709 | wikidoc | Midkine | Midkine
Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a protein that in humans is encoded by the MDK gene.
Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentally important retinoic acid-responsive gene product strongly induced during mid-gestation, hence the name midkine. Restricted mainly to certain tissues in the normal adult, it is strongly induced during oncogenesis, inflammation and tissue repair.
MK is pleiotropic, capable of exerting activities such as cell proliferation, cell migration, angiogenesis and fibrinolysis. A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP1), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor.
# Role in cancer
MK appears to enhance the angiogenic and proliferative activities of cancer cells. The expression of MK (mRNA and protein expression) has been found to be elevated in multiple cancer types, such as neuroblastoma, glioblastoma, Wilms’ tumors, thyroid papillary carcinomas, colorectal, liver, ovary, bladder, breast, lung, esophageal, stomach, and prostate cancers. Serum MK in normal individuals is usually less than 0.5-0.6 ng/ml, whereas patients with these malignancies have much higher levels than this. In some cases, these elevated levels of MK also indicate a poorer prognosis of the disease, such as in neuroblastoma, gliablastoma, and bladder carcinomas. In neuroblastoma, for example, the levels of MK are elevated about three times the level in Stage 4 of the cancer (one of the final stages) than they are in Stage 1.
In neuroblastoma, MK has been found to be over expressed in the cancer cells that are resistant to chemotherapeutic drugs. The resistance to chemotherapy seems to be reversible by administering chemo-resensitization drugs, such as verapamil, which acts not via MK alteration, but by inhibiting the P-glycoprotein pump that exports cytotoxins out of cells. Since chemotherapeutic drugs are cytotoxic, the drugs administered are also exported by this pump, rendering the chemotherapy ineffective. It has been found that when the neuroblastoma cells that are resistant to chemotherapy are grown in co-culture with the wild type (WT), or chemotherapy-sensitive cells, the resistance to chemotherapy is conferred to the wild type cells, and thus no cell death or senescence occurs in either cell type, despite the chemotherapeutic treatment. MK has been identified as one of the factors that “transfers” this chemoresistance from the resistant cells to the WT cells.
MK is a secreted protein, and is therefore found in the microenvironment (media) of the resistant neuroblastoma cells. Following co-culture experiments and the determination that MK was one of the factors that was conferring chemo-resistance to the wild, non-resistant cell type, the gene for MK was transfected into WT cells to determine if MK was overexpressed in the WT cells themselves, would the cells become resistant to chemotherapy independent of resistant cell influence. The tests further confirmed that MK specifically increased chemotherapeutic resistance in the transfected WT-MK cells versus regular WT cells, confirming the specific chemoresistant properties of MK.
In addition, the mechanism for such anti-apoptotic (anti-cell death) activity was studied, specifically using the chemotherapeutic Doxorubicin (Adriamycin) on osteosarcoma (Saos2) cells. Doxorubicin works by putting rampant cancer cells into a senescent state. MK, in WT-MK transfected cells versus WT cells, seemed to activate PKB (Akt), mTOR, and Bad protein, while it inactivated caspase-3. PKB, mTOR, and Bad are all elements associated with the cell cycle survival pathway, whereas caspase-3 is important in the apoptotic pathway (cell death). This indicates that MK caused the cells to initiate the survival pathway (via PKB, mTOR, and Bad activation) and inhibit the senescent or apoptotic pathway (via inhibiting caspase-3) encouraging the chemoresistance seen in resistant cells and in the co-culture experiments. The activation and inhibition of these particular factors clearly is maintaining the immortal quality inherent in cancer cells and specifically in the resistant cell types. Stat-3, however, which is another survival pathway factor, does not appear to have any change in activation between the wild type cells and the MK-transfected WT cells, as was initially believed from a previous study.
MK may potentially be indirectly targeted as a cancer treatment as a result of its cancerous proliferation properties. Drugs by the name of anti-cancer aptamers have been created to inhibit to proteins involved in MK’s cancer cell “activation”. Specifically, the extra-cellular matrix (ECM) protein nucleolin has been targeted with an aptamer that would bind nucleolin and prevent MK from being transported into cancerous cell nuclei, preventing the protein from enhancing the cancerous properties of the cell. Miyakawa et al. have successfully established the method to prepare the MDK specific RNA aptamers by the use of the recombinant midkine and pleiotrophin.
Mdk is also a tumor antigen able to induce CD8 and CD4 T cell responses (Kerzerho and al. 2010 Journal of Immunology)
# HIV infection
Midkine binds to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.
# Trivia
- In the Japanese film "L: Change the World", Midkine is used as a major plot element, as it is used in a vaccine to treat the ebola virus combined with influenza, from spreading. | Midkine
Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a protein that in humans is encoded by the MDK gene.[1]
Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentally important retinoic acid-responsive gene product strongly induced during mid-gestation, hence the name midkine. Restricted mainly to certain tissues in the normal adult, it is strongly induced during oncogenesis, inflammation and tissue repair.
MK is pleiotropic, capable of exerting activities such as cell proliferation, cell migration, angiogenesis and fibrinolysis. A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP1), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor.[2]
# Role in cancer
MK appears to enhance the angiogenic and proliferative activities of cancer cells.[3] The expression of MK (mRNA and protein expression) has been found to be elevated in multiple cancer types, such as neuroblastoma, glioblastoma, Wilms’ tumors, thyroid papillary carcinomas,[3] colorectal, liver, ovary, bladder, breast, lung, esophageal, stomach, and prostate cancers.[4] Serum MK in normal individuals is usually less than 0.5-0.6 ng/ml, whereas patients with these malignancies have much higher levels than this. In some cases, these elevated levels of MK also indicate a poorer prognosis of the disease, such as in neuroblastoma, gliablastoma, and bladder carcinomas.[5] In neuroblastoma, for example, the levels of MK are elevated about three times the level in Stage 4 of the cancer (one of the final stages) than they are in Stage 1.[5]
In neuroblastoma, MK has been found to be over expressed in the cancer cells that are resistant to chemotherapeutic drugs.[6][7] The resistance to chemotherapy seems to be reversible by administering chemo-resensitization drugs, such as verapamil,[8] which acts not via MK alteration, but by inhibiting the P-glycoprotein pump that exports cytotoxins out of cells.[9] Since chemotherapeutic drugs are cytotoxic, the drugs administered are also exported by this pump, rendering the chemotherapy ineffective.[9] It has been found that when the neuroblastoma cells that are resistant to chemotherapy are grown in co-culture with the wild type (WT), or chemotherapy-sensitive cells, the resistance to chemotherapy is conferred to the wild type cells, and thus no cell death or senescence occurs in either cell type,[6] despite the chemotherapeutic treatment. MK has been identified as one of the factors that “transfers” this chemoresistance from the resistant cells to the WT cells.[7]
MK is a secreted protein, and is therefore found in the microenvironment (media) of the resistant neuroblastoma cells.[7] Following co-culture experiments and the determination that MK was one of the factors that was conferring chemo-resistance to the wild, non-resistant cell type,[7] the gene for MK was transfected into WT cells to determine if MK was overexpressed in the WT cells themselves, would the cells become resistant to chemotherapy independent of resistant cell influence. The tests further confirmed that MK specifically increased chemotherapeutic resistance in the transfected WT-MK cells versus regular WT cells, confirming the specific chemoresistant properties of MK.[6]
In addition, the mechanism for such anti-apoptotic (anti-cell death) activity was studied, specifically using the chemotherapeutic Doxorubicin (Adriamycin) on osteosarcoma (Saos2) cells.[6] Doxorubicin works by putting rampant cancer cells into a senescent state. MK, in WT-MK transfected cells versus WT cells, seemed to activate PKB (Akt), mTOR, and Bad protein, while it inactivated caspase-3.[6] PKB, mTOR, and Bad are all elements associated with the cell cycle survival pathway, whereas caspase-3 is important in the apoptotic pathway (cell death).[6] This indicates that MK caused the cells to initiate the survival pathway (via PKB, mTOR, and Bad activation) and inhibit the senescent or apoptotic pathway (via inhibiting caspase-3)[6] encouraging the chemoresistance seen in resistant cells and in the co-culture experiments. The activation and inhibition of these particular factors clearly is maintaining the immortal quality inherent in cancer cells and specifically in the resistant cell types. Stat-3, however, which is another survival pathway factor, does not appear to have any change in activation between the wild type cells and the MK-transfected WT cells,[6] as was initially believed from a previous study.[7]
MK may potentially be indirectly targeted as a cancer treatment as a result of its cancerous proliferation properties.[10] Drugs by the name of anti-cancer aptamers have been created to inhibit to proteins involved in MK’s cancer cell “activation”. Specifically, the extra-cellular matrix (ECM) protein nucleolin has been targeted with an aptamer that would bind nucleolin and prevent MK from being transported into cancerous cell nuclei, preventing the protein from enhancing the cancerous properties of the cell.[10] Miyakawa et al. have successfully established the method to prepare the MDK specific RNA aptamers[11] by the use of the recombinant midkine[12] and pleiotrophin.[13]
Mdk is also a tumor antigen able to induce CD8 and CD4 T cell responses (Kerzerho and al. 2010 Journal of Immunology)
# HIV infection
Midkine binds to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.[14]
# Trivia
- In the Japanese film "L: Change the World", Midkine is used as a major plot element, as it is used in a vaccine to treat the ebola virus combined with influenza, from spreading. | https://www.wikidoc.org/index.php/Midkine | |
26581fe3040e333d3cee92a98b212f6ff314f79e | wikidoc | Mineral | Mineral
A mineral is a naturally occurring substance formed through geological processes that has a characteristic chemical composition, a highly ordered atomic structure and specific physical properties. A rock, by comparison, is an aggregate of minerals and need not have a specific chemical composition. Minerals range in composition from pure elements and simple salts to very complex silicates with thousands of known forms. The study of minerals is called mineralogy.
# Mineral definition and classification
To be classified as a "true" mineral, a substance must be a solid and have a crystalline structure. It must also be a naturally occurring, homogeneous substance with a defined chemical composition. Traditional definitions excluded organically derived material. However, the International Mineralogical Association in 1995 adopted a new definition:
The modern classifications include an organic class - in both the new Dana and the Strunz classification schemes.
The chemical composition may vary between end members of a mineral system. For example the plagioclase feldspars comprise a continuous series from sodium-rich albite (NaAlSi3O8) to calcium-rich anorthite (CaAl2Si2O8) with four recognized intermediate compositions between. Mineral-like substances that don't strictly meet the definition are sometimes classified as mineraloids. Other natural-occurring substances are nonminerals. Industrial minerals is a market term and refers to commercially valuable mined materials (see also Minerals and Rocks section below).
A crystal structure is the orderly geometric spatial arrangement of atoms in the internal structure of a mineral. There are 14 basic crystal lattice arrangements of atoms in three dimensions, and these are referred to as the 14 "Bravais lattices". Each of these lattices can be classified into one of the six crystal systems, and all crystal structures currently recognized fit in one Bravais lattice and one crystal system. This crystal structure is based on regular internal atomic or ionic arrangement that is often expressed in the geometric form that the crystal takes. Even when the mineral grains are too small to see or are irregularly shaped, the underlying crystal structure is always periodic, and can be determined by X-ray diffraction.
Chemistry and crystal structure together define a mineral. In fact, two or more minerals may have the same chemical composition, but differ in crystal structure (these are known as polymorphs). For example, pyrite and marcasite are both iron sulfide, but their arrangement of atoms differs. Similarly, some minerals have different chemical compositions, but the same crystal structure: for example, halite (made from sodium and chlorine), galena (made from lead and sulfur) and periclase (made from magnesium and oxygen) all share the same cubic crystal structure.
Crystal structure greatly influences a mineral's physical properties. For example, though diamond and graphite have the same composition (both are pure carbon), graphite is very soft, while diamond is the hardest of all known minerals. This happens because the carbon atoms in graphite are arranged into sheets which can slide easily past each other, while the carbon atoms in diamond form a strong, interlocking three-dimensional network.
There are currently more than 4,000 known minerals, according to the International Mineralogical Association, which is responsible for the approval of and naming of new mineral species found in nature. Of these, perhaps 150 can be called "common," 50 are "occasional," and the rest are "rare" to "extremely rare."
## Differences between minerals and rocks
A mineral is a naturally occurring, inorganic solid with a definite chemical composition and a specific crystalline structure. A rock is an aggregate of one or more minerals. (A rock may also include organic remains and mineraloids.) Some rocks are predominantly composed of just one mineral. For example, limestone is a sedimentary rock composed almost entirely of the mineral calcite. Other rocks contain many minerals, and the specific minerals in a rock can vary widely. Some minerals, like quartz, mica or feldspar are common, while others have been found in only one or two locations worldwide. The vast majority of the rocks of the Earth's crust consist of quartz, feldspar, mica, chlorite, kaolin, calcite, epidote, olivine, augite, hornblende, magnetite, hematite, limonite and a few other minerals. Over half of the mineral species known are so rare that they have only been found in a handful of samples, and many are known from only one or two small grains.
Commercially valuable minerals and rocks are referred to as industrial minerals. Rocks from which minerals are mined for economic purposes are referred to as ores (the rocks and minerals that remain, after the desired mineral has been separated from the ore, are referred to as tailings).
### Mineral composition of rocks
A main determining factor in the formation of minerals in a rock mass is the chemical composition of the mass, for a certain mineral can be formed only when the necessary elements are present in the rock. Calcite is most common in limestones, as these consist essentially of calcium carbonate; quartz is common in sandstones and in certain igneous rocks which contain a high percentage of silica.
Other factors are of equal importance in determining the natural association or paragenesis of rock-forming minerals, principally the mode of origin of the rock and the stages through which it has passed in attaining its present condition. Two rock masses may have very much the same bulk composition and yet consist of entirely different assemblages of minerals. The tendency is always for those compounds to be formed which are stable under the conditions under which the rock mass originated. A granite arises by the consolidation of a molten magma at high temperatures and great pressures and its component minerals are those stable under such conditions. Exposed to moisture, carbonic acid and other subaerial agents at the ordinary temperatures of the Earth's surface, some of these original minerals, such as quartz and white mica are relatively stable and remain unaffected; others weather or decay and are replaced by new combinations. The feldspar passes into kaolinite, muscovite and quartz, and any mafic minerals such as pyroxenes, amphiboles or biotite have been present they are often altered to chlorite, epidote, rutile and other substances. These changes are accompanied by disintegration, and the rock falls into a loose, incoherent, earthy mass which may be regarded as a sand or soil. The materials thus formed may be washed away and deposited as sandstone or siltstone. The structure of the original rock is now replaced by a new one; the mineralogical constitution is profoundly altered; but the bulk chemical composition may not be very different. The sedimentary rock may again undergo metamorphism. If penetrated by igneous rocks it may be recrystallized or, if subjected to enormous pressures with heat and movement during mountain building, it may be converted into a gneiss not very different in mineralogical composition though radically different in structure to the granite which was its original state.
## Physical properties of minerals
Classifying minerals can range from simple to very difficult. A mineral can be identified by several physical properties, some of them being sufficient for full identification without equivocation. In other cases, minerals can only be classified by more complex chemical or X-ray diffraction analysis; these methods, however, can be costly and time-consuming.
Physical properties commonly used are:
- Crystal structure and habit: See the above discussion of crystal structure. A mineral may show good crystal habit or form, or it may be massive, granular or compact with only microscopically visible crystals.
- Hardness: the physical hardness of a mineral is usually measured according to the Mohs scale. This scale is relative and goes from 1 to 10. Minerals with a given Mohs hardness can scratch the surface of any mineral that has a lower hardness than itself.
- Moh's Hardness scale:
- Moh's Hardness scale:
- Talc Mg3Si4O10(OH)2
- Gypsum CaSO4·2H2O
- Calcite CaCO3
- Fluorite CaF2
- Apatite Ca5(PO4)3(OH,Cl,F)
- Orthoclase KAlSi3O8
- Quartz SiO2
- Topaz Al2SiO4(OH,F)2
- Corundum Al2O3
- Diamond C (pure carbon)
- Luster indicates the way a mineral's surface interacts with light and can range from dull to glassy (vitreous).
Metallic -high reflectivity like metal: galena and pyrite
Sub-metallic -slightly less than metallic reflectivity: magnetite
Non-metallic lusters:
Adamantine - brilliant, the luster of diamond also cerussite and anglesite
Vitreous -the luster of a broken glass: quartz
Pearly - iridescent and pearl-like: talc and apophyllite
Resinous - the luster of resin: sphalerite and sulfur
Silky - a soft light shown by fibrous materials: gypsum and chrysotile
Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Metallic -high reflectivity like metal: galena and pyrite
- Sub-metallic -slightly less than metallic reflectivity: magnetite
- Non-metallic lusters:
Adamantine - brilliant, the luster of diamond also cerussite and anglesite
Vitreous -the luster of a broken glass: quartz
Pearly - iridescent and pearl-like: talc and apophyllite
Resinous - the luster of resin: sphalerite and sulfur
Silky - a soft light shown by fibrous materials: gypsum and chrysotile
Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Adamantine - brilliant, the luster of diamond also cerussite and anglesite
- Vitreous -the luster of a broken glass: quartz
- Pearly - iridescent and pearl-like: talc and apophyllite
- Resinous - the luster of resin: sphalerite and sulfur
- Silky - a soft light shown by fibrous materials: gypsum and chrysotile
- Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Color indicates the appearance of the mineral in reflected light or transmitted light for translucent minerals (i.e. what it looks like to the naked eye).
Iridescence - the play of colors due to surface or internal interference. Labradorite exhibits internal iridescence whereas hematite and sphalerite often show the surface effect.
- Iridescence - the play of colors due to surface or internal interference. Labradorite exhibits internal iridescence whereas hematite and sphalerite often show the surface effect.
- Streak refers to the color of the powder a mineral leaves after rubbing it on an unglazed porcelain streak plate. Note that this is not always the same color as the original mineral.
- Cleavage describes the way a mineral may split apart along various planes. In thin sections, cleavage is visible as thin parallel lines across a mineral.
- Fracture describes how a mineral breaks when broken contrary to its natural cleavage planes.
Chonchoidal fracture is a smooth curved fracture with concentric ridges of the type shown by glass.
Hackley is jagged fracture with sharp edges.
Fibrous
Irregular
- Chonchoidal fracture is a smooth curved fracture with concentric ridges of the type shown by glass.
- Hackley is jagged fracture with sharp edges.
- Fibrous
- Irregular
- Specific gravity relates the mineral mass to the mass of an equal volume of water, namely the density of the material. While most minerals, including all the common rock-forming minerals, have a specific gravity of 2.5 - 3.5, a few are noticeably more or less dense, e.g. several sulfide minerals have high specific gravity compared to the common rock-forming minerals.
- Other properties: fluorescence (response to ultraviolet light), magnetism, radioactivity, tenacity (response to mechanical induced changes of shape or form), piezoelectricity and reactivity to dilute acids.
## Chemical properties of minerals
Minerals may be classified according to chemical composition. They are here categorized by anion group. The list below is in approximate order of their abundance in the Earth's crust. The list follows the Dana classification system.
### Silicate class
The largest group of minerals by far are the silicates (most rocks are >95% silicates), which are composed largely of silicon and oxygen, with the addition of ions such as aluminium, magnesium, iron, and calcium. Some important rock-forming silicates include the feldspars, quartz, olivines, pyroxenes, amphiboles, garnets, and micas.
### Carbonate class
The carbonate minerals consist of those minerals containing the anion (CO3)2- and include calcite and aragonite (both calcium carbonate), dolomite (magnesium/calcium carbonate) and siderite (iron carbonate). Carbonates are commonly deposited in marine settings when the shells of dead planktonic life settle and accumulate on the sea floor. Carbonates are also found in evaporitic settings (e.g. the Great Salt Lake, Utah) and also in karst regions, where the dissolution and reprecipitation of carbonates leads to the formation of caves, stalactites and stalagmites. The carbonate class also includes the nitrate and borate minerals.
### Sulfate class
Sulfates all contain the sulfate anion, SO42-. Sulfates commonly form in evaporitic settings where highly saline waters slowly evaporate, allowing the formation of both sulfates and halides at the water-sediment interface. Sulfates also occur in hydrothermal vein systems as gangue minerals along with sulfide ore minerals. Another occurrence is as secondary oxidation products of original sulfide minerals. Common sulfates include anhydrite (calcium sulfate), celestine (strontium sulfate), barite (barium sulfate), and gypsum (hydrated calcium sulfate). The sulfate class also includes the chromate, molybdate, selenate, sulfite, tellurate, and tungstate minerals.
### Halide class
The halides are the group of minerals forming the natural salts and include fluorite (calcium fluoride), halite (sodium chloride), sylvite (potassium chloride), and sal ammoniac (ammonium chloride). Halides, like sulfates, are commonly found in evaporitic settings such as playa lakes and landlocked seas such as the Dead Sea and Great Salt Lake. The halide class includes the fluoride, chloride, bromide and iodide minerals.
### Oxide class
Oxides are extremely important in mining as they form many of the ores from which valuable metals can be extracted. They also carry the best record of changes in the Earth's magnetic field. They commonly occur as precipitates close to the Earth's surface, oxidation products of other minerals in the near surface weathering zone, and as accessory minerals in igneous rocks of the crust and mantle. Common oxides include hematite (iron oxide), magnetite (iron oxide), chromite (iron chromium oxide), spinel (magnesium aluminium oxide - a common component of the mantle), ilmenite (iron titanium oxide), rutile (titanium dioxide), and ice (hydrogen oxide). The oxide class includes the oxide and the hydroxide minerals.
### Sulfide class
Many sulfide minerals are economically important as metal ores. Common sulfides include pyrite (iron sulfide - commonly known as fools' gold), chalcopyrite (copper iron sulfide), pentlandite (nickel iron sulfide), and galena (lead sulfide). The sulfide class also includes the selenides, the tellurides, the arsenides, the antimonides, the bismuthinides, and the sulfosalts (sulfur and a second anion such as arsenic).
### Phosphate class
The phosphate mineral group actually includes any mineral with a tetrahedral unit AO4 where A can be phosphorus, antimony, arsenic or vanadium. By far the most common phosphate is apatite which is an important biological mineral found in teeth and bones of many animals. The phosphate class includes the phosphate, arsenate, vanadate, and antimonate minerals.
### Element class
The elemental group includes metals and intermetallic elements (gold, silver, copper), semi-metals and non-metals (antimony, bismuth, graphite, sulfur). This group also includes natural alloys, such as electrum (a natural alloy of gold and silver), phosphides, silicides, nitrides and carbides (which are usually only found naturally in a few rare meteorites).
### Organic class
The organic mineral class includes biogenic substances in which geological processes have been a part of the genesis or origin of the existing compound. Minerals of the organic class include various oxalates, mellitates, citrates, cyanates, acetates, formates, hydrocarbons and other miscellaneous species.
Examples include whewellite, moolooite, mellite, fichtelite, carpathite, evenkite and abelsonite. | Mineral
Template:Pp-semi-vandalism
A mineral is a naturally occurring substance formed through geological processes that has a characteristic chemical composition, a highly ordered atomic structure and specific physical properties. A rock, by comparison, is an aggregate of minerals and need not have a specific chemical composition. Minerals range in composition from pure elements and simple salts to very complex silicates with thousands of known forms.[1] The study of minerals is called mineralogy.
# Mineral definition and classification
To be classified as a "true" mineral, a substance must be a solid and have a crystalline structure. It must also be a naturally occurring, homogeneous substance with a defined chemical composition. Traditional definitions excluded organically derived material. However, the International Mineralogical Association in 1995 adopted a new definition:
The modern classifications include an organic class - in both the new Dana and the Strunz classification schemes.[3][4]
The chemical composition may vary between end members of a mineral system. For example the plagioclase feldspars comprise a continuous series from sodium-rich albite (NaAlSi3O8) to calcium-rich anorthite (CaAl2Si2O8) with four recognized intermediate compositions between. Mineral-like substances that don't strictly meet the definition are sometimes classified as mineraloids. Other natural-occurring substances are nonminerals. Industrial minerals is a market term and refers to commercially valuable mined materials (see also Minerals and Rocks section below).
A crystal structure is the orderly geometric spatial arrangement of atoms in the internal structure of a mineral. There are 14 basic crystal lattice arrangements of atoms in three dimensions, and these are referred to as the 14 "Bravais lattices". Each of these lattices can be classified into one of the six crystal systems, and all crystal structures currently recognized fit in one Bravais lattice and one crystal system. This crystal structure is based on regular internal atomic or ionic arrangement that is often expressed in the geometric form that the crystal takes. Even when the mineral grains are too small to see or are irregularly shaped, the underlying crystal structure is always periodic, and can be determined by X-ray diffraction.
Chemistry and crystal structure together define a mineral. In fact, two or more minerals may have the same chemical composition, but differ in crystal structure (these are known as polymorphs). For example, pyrite and marcasite are both iron sulfide, but their arrangement of atoms differs. Similarly, some minerals have different chemical compositions, but the same crystal structure: for example, halite (made from sodium and chlorine), galena (made from lead and sulfur) and periclase (made from magnesium and oxygen) all share the same cubic crystal structure.
Crystal structure greatly influences a mineral's physical properties. For example, though diamond and graphite have the same composition (both are pure carbon), graphite is very soft, while diamond is the hardest of all known minerals. This happens because the carbon atoms in graphite are arranged into sheets which can slide easily past each other, while the carbon atoms in diamond form a strong, interlocking three-dimensional network.
There are currently more than 4,000 known minerals, according to the International Mineralogical Association, which is responsible for the approval of and naming of new mineral species found in nature. Of these, perhaps 150 can be called "common," 50 are "occasional," and the rest are "rare" to "extremely rare."
## Differences between minerals and rocks
A mineral is a naturally occurring, inorganic solid with a definite chemical composition and a specific crystalline structure. A rock is an aggregate of one or more minerals. (A rock may also include organic remains and mineraloids.) Some rocks are predominantly composed of just one mineral. For example, limestone is a sedimentary rock composed almost entirely of the mineral calcite. Other rocks contain many minerals, and the specific minerals in a rock can vary widely. Some minerals, like quartz, mica or feldspar are common, while others have been found in only one or two locations worldwide. The vast majority of the rocks of the Earth's crust consist of quartz, feldspar, mica, chlorite, kaolin, calcite, epidote, olivine, augite, hornblende, magnetite, hematite, limonite and a few other minerals.[5] Over half of the mineral species known are so rare that they have only been found in a handful of samples, and many are known from only one or two small grains.
Commercially valuable minerals and rocks are referred to as industrial minerals. Rocks from which minerals are mined for economic purposes are referred to as ores (the rocks and minerals that remain, after the desired mineral has been separated from the ore, are referred to as tailings).
### Mineral composition of rocks
A main determining factor in the formation of minerals in a rock mass is the chemical composition of the mass, for a certain mineral can be formed only when the necessary elements are present in the rock. Calcite is most common in limestones, as these consist essentially of calcium carbonate; quartz is common in sandstones and in certain igneous rocks which contain a high percentage of silica.
Other factors are of equal importance in determining the natural association or paragenesis of rock-forming minerals, principally the mode of origin of the rock and the stages through which it has passed in attaining its present condition. Two rock masses may have very much the same bulk composition and yet consist of entirely different assemblages of minerals. The tendency is always for those compounds to be formed which are stable under the conditions under which the rock mass originated. A granite arises by the consolidation of a molten magma at high temperatures and great pressures and its component minerals are those stable under such conditions. Exposed to moisture, carbonic acid and other subaerial agents at the ordinary temperatures of the Earth's surface, some of these original minerals, such as quartz and white mica are relatively stable and remain unaffected; others weather or decay and are replaced by new combinations. The feldspar passes into kaolinite, muscovite and quartz, and any mafic minerals such as pyroxenes, amphiboles or biotite have been present they are often altered to chlorite, epidote, rutile and other substances. These changes are accompanied by disintegration, and the rock falls into a loose, incoherent, earthy mass which may be regarded as a sand or soil. The materials thus formed may be washed away and deposited as sandstone or siltstone. The structure of the original rock is now replaced by a new one; the mineralogical constitution is profoundly altered; but the bulk chemical composition may not be very different. The sedimentary rock may again undergo metamorphism. If penetrated by igneous rocks it may be recrystallized or, if subjected to enormous pressures with heat and movement during mountain building, it may be converted into a gneiss not very different in mineralogical composition though radically different in structure to the granite which was its original state.[5]
## Physical properties of minerals
Classifying minerals can range from simple to very difficult. A mineral can be identified by several physical properties, some of them being sufficient for full identification without equivocation. In other cases, minerals can only be classified by more complex chemical or X-ray diffraction analysis; these methods, however, can be costly and time-consuming.
Physical properties commonly used are:[1]
- Crystal structure and habit: See the above discussion of crystal structure. A mineral may show good crystal habit or form, or it may be massive, granular or compact with only microscopically visible crystals.
- Hardness: the physical hardness of a mineral is usually measured according to the Mohs scale. This scale is relative and goes from 1 to 10. Minerals with a given Mohs hardness can scratch the surface of any mineral that has a lower hardness than itself.
- Moh's Hardness scale:[6]
- Moh's Hardness scale:[6]
- Talc Mg3Si4O10(OH)2
- Gypsum CaSO4·2H2O
- Calcite CaCO3
- Fluorite CaF2
- Apatite Ca5(PO4)3(OH,Cl,F)
- Orthoclase KAlSi3O8
- Quartz SiO2
- Topaz Al2SiO4(OH,F)2
- Corundum Al2O3
- Diamond C (pure carbon)
- Luster indicates the way a mineral's surface interacts with light and can range from dull to glassy (vitreous).
Metallic -high reflectivity like metal: galena and pyrite
Sub-metallic -slightly less than metallic reflectivity: magnetite
Non-metallic lusters:
Adamantine - brilliant, the luster of diamond also cerussite and anglesite
Vitreous -the luster of a broken glass: quartz
Pearly - iridescent and pearl-like: talc and apophyllite
Resinous - the luster of resin: sphalerite and sulfur
Silky - a soft light shown by fibrous materials: gypsum and chrysotile
Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Metallic -high reflectivity like metal: galena and pyrite
- Sub-metallic -slightly less than metallic reflectivity: magnetite
- Non-metallic lusters:
Adamantine - brilliant, the luster of diamond also cerussite and anglesite
Vitreous -the luster of a broken glass: quartz
Pearly - iridescent and pearl-like: talc and apophyllite
Resinous - the luster of resin: sphalerite and sulfur
Silky - a soft light shown by fibrous materials: gypsum and chrysotile
Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Adamantine - brilliant, the luster of diamond also cerussite and anglesite
- Vitreous -the luster of a broken glass: quartz
- Pearly - iridescent and pearl-like: talc and apophyllite
- Resinous - the luster of resin: sphalerite and sulfur
- Silky - a soft light shown by fibrous materials: gypsum and chrysotile
- Dull/earthy -shown by finely crystallized minerals: the kidney ore variety of hematite
- Color indicates the appearance of the mineral in reflected light or transmitted light for translucent minerals (i.e. what it looks like to the naked eye).
Iridescence - the play of colors due to surface or internal interference. Labradorite exhibits internal iridescence whereas hematite and sphalerite often show the surface effect.
- Iridescence - the play of colors due to surface or internal interference. Labradorite exhibits internal iridescence whereas hematite and sphalerite often show the surface effect.
- Streak refers to the color of the powder a mineral leaves after rubbing it on an unglazed porcelain streak plate. Note that this is not always the same color as the original mineral.
- Cleavage describes the way a mineral may split apart along various planes. In thin sections, cleavage is visible as thin parallel lines across a mineral.
- Fracture describes how a mineral breaks when broken contrary to its natural cleavage planes.
Chonchoidal fracture is a smooth curved fracture with concentric ridges of the type shown by glass.
Hackley is jagged fracture with sharp edges.
Fibrous
Irregular
- Chonchoidal fracture is a smooth curved fracture with concentric ridges of the type shown by glass.
- Hackley is jagged fracture with sharp edges.
- Fibrous
- Irregular
- Specific gravity relates the mineral mass to the mass of an equal volume of water, namely the density of the material. While most minerals, including all the common rock-forming minerals, have a specific gravity of 2.5 - 3.5, a few are noticeably more or less dense, e.g. several sulfide minerals have high specific gravity compared to the common rock-forming minerals.
- Other properties: fluorescence (response to ultraviolet light), magnetism, radioactivity, tenacity (response to mechanical induced changes of shape or form), piezoelectricity and reactivity to dilute acids.
## Chemical properties of minerals
Minerals may be classified according to chemical composition. They are here categorized by anion group. The list below is in approximate order of their abundance in the Earth's crust. The list follows the Dana classification system.[1][7]
### Silicate class
The largest group of minerals by far are the silicates (most rocks are >95% silicates), which are composed largely of silicon and oxygen, with the addition of ions such as aluminium, magnesium, iron, and calcium. Some important rock-forming silicates include the feldspars, quartz, olivines, pyroxenes, amphiboles, garnets, and micas.
### Carbonate class
The carbonate minerals consist of those minerals containing the anion (CO3)2- and include calcite and aragonite (both calcium carbonate), dolomite (magnesium/calcium carbonate) and siderite (iron carbonate). Carbonates are commonly deposited in marine settings when the shells of dead planktonic life settle and accumulate on the sea floor. Carbonates are also found in evaporitic settings (e.g. the Great Salt Lake, Utah) and also in karst regions, where the dissolution and reprecipitation of carbonates leads to the formation of caves, stalactites and stalagmites. The carbonate class also includes the nitrate and borate minerals.
### Sulfate class
Sulfates all contain the sulfate anion, SO42-. Sulfates commonly form in evaporitic settings where highly saline waters slowly evaporate, allowing the formation of both sulfates and halides at the water-sediment interface. Sulfates also occur in hydrothermal vein systems as gangue minerals along with sulfide ore minerals. Another occurrence is as secondary oxidation products of original sulfide minerals. Common sulfates include anhydrite (calcium sulfate), celestine (strontium sulfate), barite (barium sulfate), and gypsum (hydrated calcium sulfate). The sulfate class also includes the chromate, molybdate, selenate, sulfite, tellurate, and tungstate minerals.
### Halide class
The halides are the group of minerals forming the natural salts and include fluorite (calcium fluoride), halite (sodium chloride), sylvite (potassium chloride), and sal ammoniac (ammonium chloride). Halides, like sulfates, are commonly found in evaporitic settings such as playa lakes and landlocked seas such as the Dead Sea and Great Salt Lake. The halide class includes the fluoride, chloride, bromide and iodide minerals.
### Oxide class
Oxides are extremely important in mining as they form many of the ores from which valuable metals can be extracted. They also carry the best record of changes in the Earth's magnetic field. They commonly occur as precipitates close to the Earth's surface, oxidation products of other minerals in the near surface weathering zone, and as accessory minerals in igneous rocks of the crust and mantle. Common oxides include hematite (iron oxide), magnetite (iron oxide), chromite (iron chromium oxide), spinel (magnesium aluminium oxide - a common component of the mantle), ilmenite (iron titanium oxide), rutile (titanium dioxide), and ice (hydrogen oxide). The oxide class includes the oxide and the hydroxide minerals.
### Sulfide class
Many sulfide minerals are economically important as metal ores. Common sulfides include pyrite (iron sulfide - commonly known as fools' gold), chalcopyrite (copper iron sulfide), pentlandite (nickel iron sulfide), and galena (lead sulfide). The sulfide class also includes the selenides, the tellurides, the arsenides, the antimonides, the bismuthinides, and the sulfosalts (sulfur and a second anion such as arsenic).
### Phosphate class
The phosphate mineral group actually includes any mineral with a tetrahedral unit AO4 where A can be phosphorus, antimony, arsenic or vanadium. By far the most common phosphate is apatite which is an important biological mineral found in teeth and bones of many animals. The phosphate class includes the phosphate, arsenate, vanadate, and antimonate minerals.
### Element class
The elemental group includes metals and intermetallic elements (gold, silver, copper), semi-metals and non-metals (antimony, bismuth, graphite, sulfur). This group also includes natural alloys, such as electrum (a natural alloy of gold and silver), phosphides, silicides, nitrides and carbides (which are usually only found naturally in a few rare meteorites).
### Organic class
The organic mineral class includes biogenic substances in which geological processes have been a part of the genesis or origin of the existing compound.[2] Minerals of the organic class include various oxalates, mellitates, citrates, cyanates, acetates, formates, hydrocarbons and other miscellaneous species.[3]
Examples include whewellite, moolooite, mellite, fichtelite, carpathite, evenkite and abelsonite. | https://www.wikidoc.org/index.php/Mineral | |
445e0687bec684c256a707a282baa3b0d5e5962a | wikidoc | mir-143 | mir-143
In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by a several mechanisms. mir–143 is highly conserved in vertebrates. mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.
# Genomic location
mir– 143 is located on chromosome 5 position 33 in the human genome. mir-143 is located very close to mir-145 in the genome and it is speculated that they are transcribed as a bicistronic unit. Their co-transcription means they are frequently studied together in the same cellular pathways and diseases.
# Expression
mir–143 is a direct transcriptional target of the serum response factor, myocardin and nkx2-5. mir-143 expression is also thought to be controlled epigenetically through heart beat.
"Both miR-143 and miR-145 were transcribed bicistronically and both are expressed in the cardiomyocytes during cardiac development. They are also expressed in the smooth muscle cells of the adults . The biogenesis of miR-143/145 was transcribed by the transcription factor, serum response factor (SRF), which binds to the CArG box of DNA with two cofactors, myocardin and myocardin-related transcription factors."
# Targets
These are known genetic targets for mir–143 and its effect on them:
- Klf4 – Promotes transcription.
- ELK1 – Promotes transcription.
- ADD3 – Represses transcription. F-actin capping protein.
- FNDC38 – Represses transcription. Tumour metastasis.
- Raldh2/aldh1a2 – Represses transcription. Involved in heart tube organization.
- rxrab – Represses transcription. Involved in heart tube organization.
- KLF5 – Unknown has conserved miR – 143 binding site.
- MAP3K7– Unknown has conserved miR – 143 binding site.
- TARDBP – Unknown has conserved miR – 143 binding site.
- UBE2E3– Unknown has conserved miR – 143 binding site.
# Cardiogenesis
mir-143 is thought to play an important role in cardiac morphogenesis. mir–143 was found to be the most enriched miRNA in mouse embryonic stem cells that were differentiating into cardiac progenitor cells. It is a direct transcriptional target of serum response factor, myocardin and nkx2-5. Research has shown that mir-143 plays an important role in smooth muscle cell fate. It is co-transcribed with miR-145 in cardiac progenitors before becoming vascular smooth muscle cells (VSMCs). VSMCs are unusual in the fact that they can switch between a proliferative or a quiescent more differentiated state. Along with mir–145, mir- 143 has been shown to target a network of transcription factors (including klf4 and elk-1) that promote differentiation and repress the proliferation of VSMCs.
MiR-143 has also been implicated in the more general morphogenesis of the heart. In zebrafish it was shown that mir-143 is required for chamber morphogenesis through repression of add3. A knockout resulted in ventricular collapse. It has also been suggested that mir-143 expression may be controlled by heart beat. In zebrafish mir-143 expression was absent when heartbeat was arrested and restored when heartbeat was reinitiated.
Understanding mir– 143 may be important for understanding vascular disease. The plasticity of VSMCs is thought to be the basis of many human vascular diseases such as atherosclerosis. It has also been shown that in human aortic aneurysms the expression of mir-143 and mir-145 were found to be significantly decreased when compared to controls.
# Cancer
Changes in mir-143 expression have frequently been implicated in cancer. However the exact nature of this relationship is not fully understood. The up-regulation of mir-143 was observed in a hepatocellular carcinoma model during tumor metastasis through repression of FNDC38. However decreased expression of mir-143 and 145 have been observed in cancer samples. Expression was shown to be decreased in a range of cancer stages, including in very early samples. This suggests that they are involved in tumorgenesis. A modified version of mir-143 (mir-143BP) with greater activity and resistance to nuclease was shown to have a tumor-suppressive effect on colorectal cancer cells. This makes miR-143 a candidate for RNA medicine for treatment of tumors.
# Acknowledgements
Initial content for this page in some instances came from Wikipedia. | mir-143
Associate Editor(s)-in-Chief: Henry A. Hoff
In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by a several mechanisms. mir–143 is highly conserved in vertebrates.[1] mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.
# Genomic location
mir– 143 is located on chromosome 5 position 33 in the human genome.[1] mir-143 is located very close to mir-145 in the genome and it is speculated that they are transcribed as a bicistronic unit.[2] Their co-transcription means they are frequently studied together in the same cellular pathways and diseases.
# Expression
mir–143 is a direct transcriptional target of the serum response factor, myocardin and nkx2-5.[2] mir-143 expression is also thought to be controlled epigenetically through heart beat.[3]
"Both miR-143 and miR-145 were transcribed bicistronically and both are expressed in the cardiomyocytes during cardiac development. They are also expressed in the smooth muscle cells of the adults [53]. The biogenesis of miR-143/145 was transcribed by the transcription factor, serum response factor (SRF), which binds to the CArG box of DNA with two cofactors, myocardin and myocardin-related transcription factors."[4]
# Targets
These are known genetic targets for mir–143 and its effect on them:
- Klf4 – Promotes transcription.[2]
- ELK1 – Promotes transcription.[2]
- ADD3 – Represses transcription. F-actin capping protein.[5]
- FNDC38 – Represses transcription. Tumour metastasis.[6]
- Raldh2/aldh1a2 – Represses transcription. Involved in heart tube organization.[3]
- rxrab – Represses transcription. Involved in heart tube organization.[3]
- KLF5 – Unknown has conserved miR – 143 binding site.[1]
- MAP3K7– Unknown has conserved miR – 143 binding site.[1]
- TARDBP – Unknown has conserved miR – 143 binding site.[1]
- UBE2E3– Unknown has conserved miR – 143 binding site.[1]
# Cardiogenesis
mir-143 is thought to play an important role in cardiac morphogenesis. mir–143 was found to be the most enriched miRNA in mouse embryonic stem cells that were differentiating into cardiac progenitor cells.[2] It is a direct transcriptional target of serum response factor, myocardin and nkx2-5.[2] Research has shown that mir-143 plays an important role in smooth muscle cell fate. It is co-transcribed with miR-145 in cardiac progenitors before becoming vascular smooth muscle cells (VSMCs). VSMCs are unusual in the fact that they can switch between a proliferative or a quiescent more differentiated state. Along with mir–145, mir- 143 has been shown to target a network of transcription factors (including klf4 and elk-1) that promote differentiation and repress the proliferation of VSMCs.[2]
MiR-143 has also been implicated in the more general morphogenesis of the heart. In zebrafish it was shown that mir-143 is required for chamber morphogenesis through repression of add3. A knockout resulted in ventricular collapse.[5] It has also been suggested that mir-143 expression may be controlled by heart beat. In zebrafish mir-143 expression was absent when heartbeat was arrested and restored when heartbeat was reinitiated.[3]
Understanding mir– 143 may be important for understanding vascular disease. The plasticity of VSMCs is thought to be the basis of many human vascular diseases such as atherosclerosis.[2] It has also been shown that in human aortic aneurysms the expression of mir-143 and mir-145 were found to be significantly decreased when compared to controls.[7]
# Cancer
Changes in mir-143 expression have frequently been implicated in cancer. However the exact nature of this relationship is not fully understood. The up-regulation of mir-143 was observed in a hepatocellular carcinoma model during tumor metastasis through repression of FNDC38.[6] However decreased expression of mir-143 and 145 have been observed in cancer samples. Expression was shown to be decreased in a range of cancer stages, including in very early samples. This suggests that they are involved in tumorgenesis.[8] A modified version of mir-143 (mir-143BP) with greater activity and resistance to nuclease was shown to have a tumor-suppressive effect on colorectal cancer cells. This makes miR-143 a candidate for RNA medicine for treatment of tumors.[8]
# Acknowledgements
Initial content for this page in some instances came from Wikipedia. | https://www.wikidoc.org/index.php/Mir-143 | |
1924c65d04a342c43a9b2bc9b9304347745dfe28 | wikidoc | mir-145 | mir-145
In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
# Targets
MicroRNAs are involved in down-regulation of a variety of target genes. Götte et al. have shown that experimental over-expression of mir-145 down-regulates the junctional cell adhesion molecule JAM-A as well as the actin bundling protein fascin. Larsson et al. showed that miR-145 targets the 3' UTR of the FLI1 gene, a finding that was later supported by Zhang et al.
# Role in cancer
miR-145 is hypothesised to be a tumor suppressor. miR-145 has been shown to be down-regulated in breast cancer. miR-145 is also involved in colon cancer and acute myeloid leukemia. | mir-145
In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.[1]
# Targets
MicroRNAs are involved in down-regulation of a variety of target genes. Götte et al. have shown that experimental over-expression of mir-145 down-regulates the junctional cell adhesion molecule JAM-A as well as the actin bundling protein fascin.[2] Larsson et al.[3] showed that miR-145 targets the 3' UTR of the FLI1 gene, a finding that was later supported by Zhang et al.[4]
# Role in cancer
miR-145 is hypothesised to be a tumor suppressor.[5] miR-145 has been shown to be down-regulated in breast cancer.[2] miR-145 is also involved in colon cancer [4][6][7] and acute myeloid leukemia.[8] | https://www.wikidoc.org/index.php/Mir-145 | |
8b381622a8ccb55e6cd843a643736e1f14d30ebd | wikidoc | Monomer | Monomer
A monomer (from Greek mono "one" and meros "part") is a small molecule that may become chemically bonded to other monomers to form a polymer.
Examples of monomers are hydrocarbons such as the alkene and arene homologous series.
Here hydrocarbon monomers such as phenylethene and ethene form polymers used as plastics like polyphenylethene (commonly known as polystyrene) and polyethene (commonly known as polyethylene or polythene). Other commercially important monomers include acrylic monomers such as acrylic acid, methyl methacrylate, and acrylamide.
Amino acids are natural monomers, and polymerize to form proteins. Glucose monomers can also polymerize to form starches, amylopectins and glycogen polymers. In this case the polymerization reaction is known as a dehydration or condensation reaction (due to the formation of water (H2O) as one of the products) where a hydrogen atom and a hydroxyl (-OH) group are lost to form H2O and an oxygen molecule bonds between each monomer unit.
The lower molecular weight compounds built from monomers are also referred to as dimers, trimers, tetramers, quadramers, pentamers, octamers, 20-mers, etc. if they have 2, 3, 4, 5, 8, or 20 monomer units, respectively. Any number of these monomer units may be indicated by the appropriate prefix, eg, decamer, being a 10-unit monomer chain or polymer. Larger numbers are often stated in English in lieu of Greek. Polymers with relatively low number of units are called oligomers. | Monomer
A monomer (from Greek mono "one" and meros "part") is a small molecule that may become chemically bonded to other monomers to form a polymer.
Examples of monomers are hydrocarbons such as the alkene and arene homologous series.
Here hydrocarbon monomers such as phenylethene and ethene form polymers used as plastics like polyphenylethene (commonly known as polystyrene) and polyethene (commonly known as polyethylene or polythene). Other commercially important monomers include acrylic monomers such as acrylic acid, methyl methacrylate, and acrylamide.
Amino acids are natural monomers, and polymerize to form proteins. Glucose monomers can also polymerize to form starches, amylopectins and glycogen polymers. In this case the polymerization reaction is known as a dehydration or condensation reaction (due to the formation of water (H2O) as one of the products) where a hydrogen atom and a hydroxyl (-OH) group are lost to form H2O and an oxygen molecule bonds between each monomer unit.
The lower molecular weight compounds built from monomers are also referred to as dimers, trimers, tetramers, quadramers, pentamers, octamers, 20-mers, etc. if they have 2, 3, 4, 5, 8, or 20 monomer units, respectively. Any number of these monomer units may be indicated by the appropriate prefix, eg, decamer, being a 10-unit monomer chain or polymer. Larger numbers are often stated in English in lieu of Greek. Polymers with relatively low number of units are called oligomers. | https://www.wikidoc.org/index.php/Monomer | |
073b3ee2aa88bc824037a48845e3f91e2e0d5a00 | wikidoc | Morphea | Morphea
Synonyms and keywords: Localized scleroderma.
# Overview
Morphea, also known as localized scleroderma, is a thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition. Morphea includes specific conditions ranging from very small plaques only involving the skin to widespread disease causing functional and cosmetic deformities. Morphea involves isolated patches of hardened skin and discriminates from systemic sclerosis by its supposed lack of internal organ involvement.
# Classification
The most widely used classification divides morphea into five general subtypes: plaque morphea, generalized morphea, linear scleroderma, bullous morphea, and deep morphea. This classification scheme does not include the mixed form of morphea in which different morphologies of skin lesions are present in the same individual. Up to 15% of morphea patients may fall into this previously unrecognized category.
# Epidemiology
Morphea is an uncommon condition that is thought to affect 1 in 100,000 people. Adequate studies on the incidence and prevalence have not been performed. Morphea also may be under-reported as physicians may be unaware of this disorder and smaller morphea plaques may be less often referred to a dermatologist or rheumatologist. As in many other connective tissue or autoimmune disorders, morphea mainly involves women with a W:M ratio of 3:1.
# Etiology
Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea. Tests for autoantibodies associated with morphea have shown results in higher frequencies of anti-histone and anti-topoisomerase IIa antibodies. Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease.
# Diagnoses of Morphea should be Distinguished from
- Annular lichenoid dermatitis of youth
- Ataxia-telangiectasia
- Atrophoderma of pasini and pierini
- Carcinoid syndrome
- Cheiroarthropathy due to diabetes mellitus
- Eosinophilia myalgia syndrome
- Eosinophilic fasciitis
- Erythema migrans
- Fixed drug eruption
- Graft versus host disease
- Inflammatory granuloma annulare
- Interstitial and granulomatous dermatitis
- Interstitial mycosis fungoides
- Keloid and hypertrophic scar
- Lichen sclerosus et atrophicus
- Linear atrophoderma of Moulin
- Linear lupus erythematosus panniculitis
- Linear melorheostosis
- Lipodermatosclerosis
- Morpheaform dermatofibrosarcoma protuberans
- Muckle-Wells syndrome
- Nephrogenic fibrosing dermopathy
- Niemann-Pick disease
- Phenylketonuria
- POEMS syndrome
- Porphyria cutanea tarda
- Primary systemic amyloidosis
- Progeria
- Radiation fibrosis
- Reflex sympathetic dystrophy
- Restrictive dermopathy
- Scleroderma
- Sclerodermoid conditions caused by chemical/toxin exposures
Polyvinyl chloride
Epoxy resins
Pesticides
Dry cleaning solvents
Silica dust
- Sclerodermoid conditions caused by iatrogenic agents
Bleomycin
Gemcitabine
L-Tryptophan
Melphalan isolated limb perfusion
Pentazocine injections
Silicone or paraffin implants
Taxanes
Uracil-Tegafur
Vitamin K injections
- Scleromyxedema
- Stiff skin syndrome
- Sweet syndrome (early)
- Werner syndrome
- Winchester syndrome
# Physical examination
## Gallery
### Skin
### Trunk
- url = >
- url = >
- url = >
- url = >
- url = >
- url = >
- url = >
- url = >
- Localized morphoea.
- Localized morphoea.
- Nodular morphoea.
- Nodular morphoea.
- url = >
- url = >
- url = >
- url = >
# Treatment
Throughout the years, many different treatments have been tried for morphea including topical, intra-lesional, and systemic corticosteroids. Antimalarials such as hydroxychloroquine or chloroquine have been used. Other immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried. Ultraviolet A (UVA) light, with or without psoralens have also been tried. UVA-1, a more specific wavelength of UVA light, is able to penetrate the deeper portions of the skin and thus, thought to soften the plaques in morphea by acting in two fashions:
- 1) by causing a systemic immunosuppression from UV light.
- 2) by inducing enzymes that naturally degrade the collagen matrix in the skin as part of natural sun-aging of the skin.
As with all of these treatments for morphea, the difficulty in assessing outcomes in an objective way has limited the interpretation of most studies involving these treatment modalities. | Morphea
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2],Kiran Singh, M.D. [3].
Synonyms and keywords: Localized scleroderma.
# Overview
Morphea, also known as localized scleroderma, is a thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition. Morphea includes specific conditions ranging from very small plaques only involving the skin to widespread disease causing functional and cosmetic deformities. Morphea involves isolated patches of hardened skin and discriminates from systemic sclerosis by its supposed lack of internal organ involvement.[1]
# Classification
The most widely used classification divides morphea into five general subtypes: plaque morphea, generalized morphea, linear scleroderma, bullous morphea, and deep morphea.[2] This classification scheme does not include the mixed form of morphea in which different morphologies of skin lesions are present in the same individual. Up to 15% of morphea patients may fall into this previously unrecognized category.[3]
# Epidemiology
Morphea is an uncommon condition that is thought to affect 1 in 100,000 people.[4] Adequate studies on the incidence and prevalence have not been performed. Morphea also may be under-reported as physicians may be unaware of this disorder and smaller morphea plaques may be less often referred to a dermatologist or rheumatologist. As in many other connective tissue or autoimmune disorders, morphea mainly involves women with a W:M ratio of 3:1.[5]
# Etiology
Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea.[3] Tests for autoantibodies associated with morphea have shown results in higher frequencies of anti-histone and anti-topoisomerase IIa antibodies.[6] Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease.[7][8][9]
# Diagnoses of Morphea should be Distinguished from
- Annular lichenoid dermatitis of youth
- Ataxia-telangiectasia
- Atrophoderma of pasini and pierini
- Carcinoid syndrome
- Cheiroarthropathy due to diabetes mellitus
- Eosinophilia myalgia syndrome
- Eosinophilic fasciitis
- Erythema migrans
- Fixed drug eruption
- Graft versus host disease
- Inflammatory granuloma annulare
- Interstitial and granulomatous dermatitis
- Interstitial mycosis fungoides
- Keloid and hypertrophic scar
- Lichen sclerosus et atrophicus
- Linear atrophoderma of Moulin
- Linear lupus erythematosus panniculitis
- Linear melorheostosis
- Lipodermatosclerosis
- Morpheaform dermatofibrosarcoma protuberans
- Muckle-Wells syndrome
- Nephrogenic fibrosing dermopathy
- Niemann-Pick disease
- Phenylketonuria
- POEMS syndrome
- Porphyria cutanea tarda
- Primary systemic amyloidosis
- Progeria
- Radiation fibrosis
- Reflex sympathetic dystrophy
- Restrictive dermopathy
- Scleroderma
- Sclerodermoid conditions caused by chemical/toxin exposures
Polyvinyl chloride
Epoxy resins
Pesticides
Dry cleaning solvents
Silica dust
- Sclerodermoid conditions caused by iatrogenic agents
Bleomycin
Gemcitabine
L-Tryptophan
Melphalan isolated limb perfusion
Pentazocine injections
Silicone or paraffin implants
Taxanes
Uracil-Tegafur
Vitamin K injections
- Scleromyxedema
- Stiff skin syndrome
- Sweet syndrome (early)
- Werner syndrome
- Winchester syndrome
# Physical examination
## Gallery
### Skin
### Trunk
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- Localized morphoea.
- Localized morphoea.
- Nodular morphoea.
- Nodular morphoea.
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=300>
# Treatment
Throughout the years, many different treatments have been tried for morphea including topical, intra-lesional, and systemic corticosteroids. Antimalarials such as hydroxychloroquine or chloroquine have been used. Other immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried. Ultraviolet A (UVA) light, with or without psoralens have also been tried. UVA-1, a more specific wavelength of UVA light, is able to penetrate the deeper portions of the skin and thus, thought to soften the plaques in morphea by acting in two fashions:
- 1) by causing a systemic immunosuppression from UV light.
- 2) by inducing enzymes that naturally degrade the collagen matrix in the skin as part of natural sun-aging of the skin.
As with all of these treatments for morphea, the difficulty in assessing outcomes in an objective way has limited the interpretation of most studies involving these treatment modalities. | https://www.wikidoc.org/index.php/Morphea | |
2b872d06c1015fcb85a6103db57a3a2c5e3e1dca | wikidoc | Motilin | Motilin
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
Motilin is secreted by endocrine Mo cells (or M cells, these are not the same as the Microfold cells (M cells) that are in Peyer's patches) that are numerous in crypts of the small intestine, especially in the duodenum and jejunum. It is released into the general circulation in humans at about 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions; and it also stimulates endogenous release of the endocrine pancreas. Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was named "motilin". Apart from in humans, the motilin receptor has been identified in the gastrointestinal tracts of pigs, rats, cows, and cats, and in the central nervous system of rabbits.
# Discovery
Motilin was discovered by J.C. Brown when he introduced alkaline solution into duodena of dogs, which caused strong gastric contractions. Brown et al. predicted that alkali could either release stimulus to activate motor activity or prevent the secretion of inhibitory hormone. They isolated a polypeptide as a by-product from purification of secretin on carboxymethyl cellulose. They named this polypeptide "Motilin".
# Structure
Motilin has 22 amino acids and molecular weight of 2698 Daltons. In extract from human gut and plasma, there are two basic forms of motilin. The first molecular form is the polypeptide of 22 amino acids. The second form, on the other hand, is larger and contains the same 22 amino acids as the first form but includes an additional carboxyl-terminus end.
The sequences of amino acids of motilin is: Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln.
The structure and dynamics of the gastrointestinal peptide hormone motilin have been studied in the presence of isotropic q = 0.5 phospholipid bicelles. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone torsion angle constraints. Dynamic properties for the 13Cα→1H vector in Leu-10 were determined for motilin specifically labeled with 13C at this position by analysis of multiple-field relaxation data. The structure reveals an ordered alpha-helical conformation between Glu-9 and Lys-20. The N-terminus is also well structured with a turn resembling that of a classical beta-turn. The 13C dynamics clearly show that motilin tumbles slowly in solution, with a correlation time characteristic of a large object.
# Stimulus
Control of motilin secretion is largely unknown, although some studies suggest that an alkaline pH in the duodenum stimulates its release. However, at low pH it inhibits gastric motor activity, whereas at high pH it has a stimulatory effect. Some studies in dogs have shown that motilin is released during fasting or interdigestive period, and intake of food during this period can prevent the secretion of motilin. Intravenous injection of glucose, which increases the release of insulin, is also found to inhibit cyclic elevation of plasma motilin. Other studies on dogs have also suggested that motilin acted as endogenous ligand in positive feedback mechanism to stimulate the release of more motilin.
# Function
The main function of motilin is to increase the migrating myoelectric complex component of gastrointestinal motility and stimulate the production of pepsin. Motilin is also called "housekeeper of the gut" because it improves peristalsis in the small intestine and clears out the gut to prepare for the next meal. A high level of motilin secreted between meals into the blood stimulates the contraction of the fundus and antrum and accelerates gastric emptying. It then contracts the gallbladder and increases the squeeze pressure of the lower esophageal sphincter. Other functions of motilin include increasing the release of pancreatic polypeptide and somatostatin
# Motilin agonists
Erythromycin and related antibiotics act as non-peptide motilin agonists, and are sometimes used for their ability to stimulate gastrointestinal motility. In the case of erythromycin, it is its hemiketal intermediate, formed after an oral dose in the low-pH environment of the stomach lumen, which directly acts on the motilin receptor. Administration of a low dose of erythromycin will induce peristalsis, which provides additional support for the conclusion that motilin secretion triggers this pattern of gastrointestinal motility, rather than results from it. However, some of erythromycin’s properties, including antibiotic activity, are not appropriate for a drug designed for chronic use over a patient's lifetime.
New motilin agonists are erythromycin-based; however, it may be that this class of drugs becomes redundant. Growth hormone secretagogue receptors share 52% of their DNA with motilin receptors, and agonists of these receptors, termed ghrelins, can bring about similar effects to motilin agonists.
Camicinal is a Motilin agonist under development.
# Related peptides
This domain is also found in ghrelin, a growth hormone secretagogue synthesised by endocrine cells in the stomach. Ghrelin stimulates growth hormone secretagogue receptors in the pituitary. These receptors are distinct from the growth hormone-releasing hormone receptors, and, thus, provide a means of controlling pituitary growth hormone release by the gastrointestinal system.
Erythromycin has an advantage over metoclopramide in gastric emptying due to lack of central nervous system side-effects. It is not approved by FDA to use for gastric emptying. For short duration for patients with diabetes and for those that must clear the stomach for any procedure, it may be used based on the physician's discretion with full understanding that it is not approved by FDA for this use.
# Human proteins
GHRL; Motilin; | Motilin
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.[2]
Motilin is secreted by endocrine Mo cells[3][4] (or M cells, these are not the same as the Microfold cells (M cells) that are in Peyer's patches) that are numerous in crypts of the small intestine, especially in the duodenum and jejunum.[5] It is released into the general circulation in humans at about 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions; and it also stimulates endogenous release of the endocrine pancreas.[6] Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was named "motilin". Apart from in humans, the motilin receptor has been identified in the gastrointestinal tracts of pigs, rats, cows, and cats, and in the central nervous system of rabbits.
# Discovery
Motilin was discovered by J.C. Brown when he introduced alkaline solution into duodena of dogs, which caused strong gastric contractions. Brown et al. predicted that alkali could either release stimulus to activate motor activity or prevent the secretion of inhibitory hormone. They isolated a polypeptide as a by-product from purification of secretin on carboxymethyl cellulose. They named this polypeptide "Motilin".[7]
# Structure
Motilin has 22 amino acids and molecular weight of 2698 Daltons. In extract from human gut and plasma, there are two basic forms of motilin. The first molecular form is the polypeptide of 22 amino acids. The second form, on the other hand, is larger and contains the same 22 amino acids as the first form but includes an additional carboxyl-terminus end.[8]
The sequences of amino acids of motilin is: Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln.[9]
The structure and dynamics of the gastrointestinal peptide hormone motilin have been studied in the presence of isotropic q = 0.5 phospholipid bicelles. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone torsion angle constraints. Dynamic properties for the 13Cα→1H vector in Leu-10 were determined for motilin specifically labeled with 13C at this position by analysis of multiple-field relaxation data. The structure reveals an ordered alpha-helical conformation between Glu-9 and Lys-20. The N-terminus is also well structured with a turn resembling that of a classical beta-turn. The 13C dynamics clearly show that motilin tumbles slowly in solution, with a correlation time characteristic of a large object.[1]
# Stimulus
Control of motilin secretion is largely unknown, although some studies suggest that an alkaline pH in the duodenum stimulates its release. However, at low pH it inhibits gastric motor activity, whereas at high pH it has a stimulatory effect. Some studies in dogs have shown that motilin is released during fasting or interdigestive period, and intake of food during this period can prevent the secretion of motilin.[10] Intravenous injection of glucose, which increases the release of insulin, is also found to inhibit cyclic elevation of plasma motilin.[11] Other studies on dogs have also suggested that motilin acted as endogenous ligand in positive feedback mechanism to stimulate the release of more motilin.[12]
# Function
The main function of motilin is to increase the migrating myoelectric complex component of gastrointestinal motility and stimulate the production of pepsin. Motilin is also called "housekeeper of the gut" because it improves peristalsis in the small intestine and clears out the gut to prepare for the next meal.[9] A high level of motilin secreted between meals into the blood stimulates the contraction of the fundus and antrum and accelerates gastric emptying. It then contracts the gallbladder and increases the squeeze pressure of the lower esophageal sphincter. Other functions of motilin include increasing the release of pancreatic polypeptide and somatostatin[13]
# Motilin agonists
Erythromycin and related antibiotics act as non-peptide motilin agonists, and are sometimes used for their ability to stimulate gastrointestinal motility. In the case of erythromycin, it is its hemiketal intermediate, formed after an oral dose in the low-pH environment of the stomach lumen, which directly acts on the motilin receptor.[14] Administration of a low dose of erythromycin will induce peristalsis, which provides additional support for the conclusion that motilin secretion triggers this pattern of gastrointestinal motility, rather than results from it. However, some of erythromycin’s properties, including antibiotic activity, are not appropriate for a drug designed for chronic use over a patient's lifetime.
New motilin agonists are erythromycin-based; however, it may be that this class of drugs becomes redundant. Growth hormone secretagogue receptors share 52% of their DNA with motilin receptors, and agonists of these receptors, termed ghrelins, can bring about similar effects to motilin agonists.
Camicinal is a Motilin agonist under development.
# Related peptides
This domain is also found in ghrelin, a growth hormone secretagogue synthesised by endocrine cells in the stomach. Ghrelin stimulates growth hormone secretagogue receptors in the pituitary. These receptors are distinct from the growth hormone-releasing hormone receptors, and, thus, provide a means of controlling pituitary growth hormone release by the gastrointestinal system.[15]
Erythromycin has an advantage over metoclopramide in gastric emptying due to lack of central nervous system side-effects. It is not approved by FDA to use for gastric emptying. For short duration for patients with diabetes and for those that must clear the stomach for any procedure, it may be used based on the physician's discretion with full understanding that it is not approved by FDA for this use.
# Human proteins
GHRL; Motilin; | https://www.wikidoc.org/index.php/Motilin | |
f1a486c44b84f7fc4847b191e923f1c58ffec0ea | wikidoc | Motofen | Motofen
Motofen is the brand name for an antiperistaltic anti-diarrheal medication, containing 1.0 mg difenoxin HCl and 0.025 mg atropine (US FDA: Schedule IV Combination). Atropine is purposely added to minimize misuse potential since difenoxin is chemically related to the opiate family, and could theoretically be misused. Although misuse or abuse is unlikely and rare, physical withdrawal symptoms may still be present if taken for long periods of time. However, both of these compounds are responsible for the medicinal effects of the medicine (both atropine and difenoxin slow gut movement).
This combination medication should not be confused with Lomotil because the active ingredients in the two medications are different compounds, except for the inclusion of atropine. Motofen is approximately 2 to 4 times more effective in treating symptoms than Lomotil (2.5 mg diphenoxylate and 0.025 mg atropine - Schedule V Combination.
# Indications and Uses
Although Motofen is officially indicated by the FDA for diarrhea, it has also been successfully used by physicians for irritable bowel syndrome (IBS), and hyperhidrosis (chronic, severe sweating).
# Side Effects, Interactions, and Misuse Potential
Side effects include (but are not limited to): drowsiness, nausea, vomiting, burning eyes, blurred vision, dry eyes, dizziness, dry mouth, epigastric distress, and constipation (a paradoxical side effect). In addition to the side effects listed above, some are caused by the presence of atropine (especially when taken in excess doses, or in children), namely: flushing, dryness in many areas, urinary retention, insomnia, headache, anxiety, hyperthermia, and tachycardia. It is these side effects produced by atropine, that makes it very undesirable for most patients to take higher amounts of the medicine.
# Dosing and Administration
Initial dosing states two tablets to be taken at first, and one tablet to be taken after each loose stool thereafter. The recommended therapeutic dosage for Motofen should not exceed 8 tablets (8 milligrams of Difenoxin). There are currently no instructions on use for Irritable Bowel Syndrome (IBS) and Hyperhidrosis, although as stated above, it has been used successfully in treating symptoms of both disorders (which can accompany each other). There was a "Motofen half-strength" tablet, containing only .5 milligrams of Difenoxin (However, containing the same amount of atropine), but is now discontinued. Therefore, only standard 1.0 milligram strength tablets are available by prescription.
# Availability, Price, and Supply
There is currently only one manufacturer of Motofen tablets: Valeant Pharmaceuticals. It acquired the drug from Amarin Pharmaceuticals in 2004. Valeant's tablets are pentagonal shaped, debossed with a "V" on one side, and vertically scored on the other side. In addition, the number "0500" is debossed bisecting the score line perpendicularly. The aforementioned debossing renders "05" and "00" on the left and right side of the score, respectively.
Motofen is higher priced than both Imodium and Lomotil, does not have a generic equivalent, and is only available by prescription in the United States (FDA). Most United States insurance companies do not include Motofen as one of their formulary drugs, causing consumers to pay the highest copay, if it is covered by their health insurance at all. The United States is currently the only country where Motofen tablets are prescribed, approved by the government, and sold. This is most likely due to the high cost of the medication itself, and the fact that similar lower-priced medicines can help ease symptoms of diarrhea (However, Loperamide and Lomotil seem less effective in treating Irritable Bowel Syndrome and Hyperhidrosis patients, if effective at all).
# Misc. Information
Strangely, Motofen is only included in the Physicians' Desk Reference (PDR) for the years 2005 and 2006 as a literal snippet entry. Nothing is said about the indications and usage, only the ingredients, current appearance (at the time of publishing), NDC#, and the quantities in which it is supplied. It is still available though, and not very hard to find at pharmacies in decent sized metropolitan areas. The pharmacist may not even know what it is, and is surprised to even find it on the shelf! | Motofen
Motofen is the brand name for an antiperistaltic anti-diarrheal medication, containing 1.0 mg difenoxin HCl and 0.025 mg atropine (US FDA: Schedule IV Combination). Atropine is purposely added to minimize misuse potential since difenoxin is chemically related to the opiate family, and could theoretically be misused. Although misuse or abuse is unlikely and rare, physical withdrawal symptoms may still be present if taken for long periods of time. However, both of these compounds are responsible for the medicinal effects of the medicine (both atropine and difenoxin slow gut movement).
This combination medication should not be confused with Lomotil because the active ingredients in the two medications are different compounds, except for the inclusion of atropine. Motofen is approximately 2 to 4 times more effective in treating symptoms than Lomotil (2.5 mg diphenoxylate and 0.025 mg atropine - Schedule V Combination.
# Indications and Uses
Although Motofen is officially indicated by the FDA for diarrhea, it has also been successfully used by physicians for irritable bowel syndrome (IBS), and hyperhidrosis (chronic, severe sweating).
# Side Effects, Interactions, and Misuse Potential
Side effects include (but are not limited to): drowsiness, nausea, vomiting, burning eyes, blurred vision, dry eyes, dizziness, dry mouth, epigastric distress, and constipation (a paradoxical side effect). In addition to the side effects listed above, some are caused by the presence of atropine (especially when taken in excess doses, or in children), namely: flushing, dryness in many areas, urinary retention, insomnia, headache, anxiety, hyperthermia, and tachycardia. It is these side effects produced by atropine, that makes it very undesirable for most patients to take higher amounts of the medicine.
# Dosing and Administration
Initial dosing states two tablets to be taken at first, and one tablet to be taken after each loose stool thereafter. The recommended therapeutic dosage for Motofen should not exceed 8 tablets (8 milligrams of Difenoxin). There are currently no instructions on use for Irritable Bowel Syndrome (IBS) and Hyperhidrosis, although as stated above, it has been used successfully in treating symptoms of both disorders (which can accompany each other). There was a "Motofen half-strength" tablet, containing only .5 milligrams of Difenoxin (However, containing the same amount of atropine), but is now discontinued. Therefore, only standard 1.0 milligram strength tablets are available by prescription.
# Availability, Price, and Supply
There is currently only one manufacturer of Motofen tablets: Valeant Pharmaceuticals. It acquired the drug from Amarin Pharmaceuticals in 2004[1]. Valeant's tablets are pentagonal shaped, debossed with a "V" on one side, and vertically scored on the other side. In addition, the number "0500" is debossed bisecting the score line perpendicularly. The aforementioned debossing renders "05" and "00" on the left and right side of the score, respectively.
Motofen is higher priced than both Imodium and Lomotil, does not have a generic equivalent, and is only available by prescription in the United States (FDA). Most United States insurance companies do not include Motofen as one of their formulary drugs, causing consumers to pay the highest copay, if it is covered by their health insurance at all. The United States is currently the only country where Motofen tablets are prescribed, approved by the government, and sold. This is most likely due to the high cost of the medication itself, and the fact that similar lower-priced medicines can help ease symptoms of diarrhea (However, Loperamide and Lomotil seem less effective in treating Irritable Bowel Syndrome and Hyperhidrosis patients, if effective at all).
# Misc. Information
Strangely, Motofen is only included in the Physicians' Desk Reference (PDR) for the years 2005 and 2006 as a literal snippet entry. Nothing is said about the indications and usage, only the ingredients, current appearance (at the time of publishing), NDC#, and the quantities in which it is supplied. It is still available though, and not very hard to find at pharmacies in decent sized metropolitan areas. The pharmacist may not even know what it is, and is surprised to even find it on the shelf! | https://www.wikidoc.org/index.php/Motofen | |
80fd26f9779324d66de8516df418dde018f992bc | wikidoc | Movicol | Movicol
A drug used in the treatment of constipation, Movicol comes in the form of a dissolvable sachet and is marketed outside the US by Norgine Ltd
The active ingredient is polyethylene glycol '3350' (also known as macrogol), which belongs to a class of drugs called osmotic laxatives. These drugs work by binding to water in the gut, thereby moistening stools making them easier to pass.
For more detailed information, including side effects and contra-indications of the drug see the British National Formulary or the references. | Movicol
A drug used in the treatment of constipation, Movicol comes in the form of a dissolvable sachet and is marketed outside the US by Norgine Ltd
The active ingredient is polyethylene glycol '3350' (also known as macrogol), which belongs to a class of drugs called osmotic laxatives. These drugs work by binding to water in the gut, thereby moistening stools making them easier to pass.
For more detailed information, including side effects and contra-indications of the drug see the British National Formulary or the references. | https://www.wikidoc.org/index.php/Movicol | |
e11a8697cae299ae330da32b29907e9393fc71b8 | wikidoc | Mucin 2 | Mucin 2
Mucin 2, oligomeric mucus gel-forming, also known as MUC2, is a protein that in humans is encoded by the MUC2 gene.
# Function
This gene encodes a member of the mucin protein family. The protein encoded by this gene, also called mucin 2, is secreted onto mucosal surfaces.
Mucin 2 is particularly prominent in the gut where it is secreted from goblet cells in the epithelial lining into the lumen of the large intestine. There, mucin 2, along with small amounts of related-mucin proteins, polymerizes into a gel of which 80% by weight is oligosaccharide side-chains that are added as post-translational modifications to the mucin proteins. This gel provides an insoluble mucous barrier that serves to protect the intestinal epithelium.
# Genetics
The mucin 2 protein features a central domain containing tandem repeats rich in threonine and proline that varies between 50 and 115 copies in different individuals. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. | Mucin 2
Mucin 2, oligomeric mucus gel-forming, also known as MUC2, is a protein that in humans is encoded by the MUC2 gene.[1][2]
# Function
This gene encodes a member of the mucin protein family. The protein encoded by this gene, also called mucin 2, is secreted onto mucosal surfaces.[1]
Mucin 2 is particularly prominent in the gut where it is secreted from goblet cells in the epithelial lining into the lumen of the large intestine. There, mucin 2, along with small amounts of related-mucin proteins, polymerizes into a gel of which 80% by weight is oligosaccharide side-chains that are added as post-translational modifications to the mucin proteins. This gel provides an insoluble mucous barrier that serves to protect the intestinal epithelium.
# Genetics
The mucin 2 protein features a central domain containing tandem repeats rich in threonine and proline that varies between 50 and 115 copies in different individuals. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.[3] | https://www.wikidoc.org/index.php/Mucin_2 | |
128aeb49cd3fff6903b00e0a56633230181033d3 | wikidoc | Mucin 4 | Mucin 4
Mucin 4 (MUC 4) is a mucin protein that in humans is encoded by the MUC4 gene. Like other mucins, MUC-4 is a high-molecular weight glycoprotein.
The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues.
MUC-4 has been found to play various roles in the progression of cancer, particularly due to its signaling and anti-adhesive properties which contribute to tumor development and metastasis. It is also found to play roles in other diseases such as endometriosis and inflammatory bowel disease. MUC-4 belongs to the human mucin family that is membrane-anchored and can range in molecular weight from 550 to 930 kDa for the actual protein, and up to 4,650 kDa with glycosylation.
# Structure
MUC-4 is an O-glycoprotein that can reach up to 2 micrometers outside the cell. MUC-4 mucins consist of a large extracellular alpha subunit that is heavily glycosylated and a beta subunit that is anchored in the cell membrane and extends into the cytosol. This beta subunit is considered an oncogene, whose role in cancer is increasingly being recognized particularly due to its involvement in signalling pathways, particularly with ErbB2 (Her2). This subunit serves as a ligand for ErbB2, which is suggested to cause the repression of apoptosis found in many cancer cells.
The large alpha subunit that is glycosylated likely confers the anti-adhesive properties to the cell, allowing for cell–cell and cell–matrix detachment in normal as well as cancerous cells. The heavy glycosylation may also serve as a reservoir for growth factors, which may become released upon degradation.
The two subunits of MUC-4 are transcribed from a single gene. Over 24 splice variants have been found for MUC4, in normal as well as abnormal tissue. Some forms are soluble, while others are membrane bound. Many polymorphisms are observed in the tandem repeat region of the alpha subunit, which has a variable number of repeats.
# Function
## Normal
In normal functioning, MUC-4 is known to play anti-adhesive roles in the body, such as in lubricating the reproductive lining. It is also found in the respiratory tract - particularly in the trachea and lung - and the digestive tract - in the esophagus and colon - as well as in the visual and auditory systems. In these roles, MUC-4 serves to protect and lubricate the epithelium, which facilitates transport and traps foreign particles. One example of its function in the reproductive lining relates to blastocyst implantation resulting from MUC4 downregulation. It is found to be overexpressed during the luteal phase of menstruation. MUC-4 may also have a role in fetal morphogenic development. It should be noted that MUC-4 is not found in the gallbladder, pancreas, or liver except in abnormal conditions such as cancer. MUC-4, however, may normally be found in bodily fluids like saliva, tears, and milk. In the soluble form, MUC-4 appears to lubricate the epithelial mucosa.
## Disease
MUC-4 is thought to play a role in cancer progression by repressing apoptosis and consequently increasing tumor cell proliferation. The molecular mechanism is thought to be through a MUC-4 complex with ERBB2 receptors, which alters downstream signaling and down regulates CDKN1B. The beta subunit of MUC-4 appears to serve as a ligand that causes the phosphorylation of ErbB2, but does not activate the MAPK or AKT pathways. MUC-4 may also affect HER2 signaling, and result in its stabilization. As a mucin, MUC-4 also alters adhesive properties of the cell. When overexpressed, the disorganization of mucins may reduce adhesion to other cells as well as the extracellular matrix, promoting cancer cell migration and metastasis.
# Role in cancer
## Pancreatic
MUC4 is often overexpressed in pancreatic adenocarcinomas and has been shown to promote tumor growth and metastasis, though the mechanism by which it does so is not known. MUC4 detection is emerging as a method to diagnose pancreatic cancer, especially since MUC4 is not detectably expressed in normal pancreas and increased expression of MUC-4 suggests a greater progression of the disease. Scientists have recently experimented with MUC4 inhibition in pancreatic cancer using drug delivery methods such as microRNAs. Such efforts have been successful at reducing EGF receptor expression, its downstream signaling, and consequently malignant behavior of the cancer cell such as migration, invasion, and cell detachment.
## Esophageal
MUC4 expression in esophageal cancer often leads to increased tumor proliferation and migration. Like with prostate cancer, increased expression of MUC4 suggests greater development of esophageal cancer. Bile acids present in gastroesophageal reflux disease are thought to contribute to this over-expression of MUC4. By inhibiting MUC-4, scientists have been able to reduce cancer cell proliferation, migration, and tumor size as well as reduce protein S100A4 expression, presenting MUC-4 as a good therapeutic target for the treatment of esophageal cancer.
## Breast
Unlike pancreatic and esophageal cancers, MUC4 expression is suppressed in the primary tumor when compared to normal cells. It, however, is found to be overexpressed in lymph node metastases. The initial reduction in MUC-4 appears to promote the transition to the primary tumor, but its subsequent increase in expression facilitate metastasis and ultimately increased malignancy
## Other
MUC4 is found to be overexpressed in papillary thyroid carcinoma, and could serve as a potential marker of malignancy and prognosis. MUC-4 is also found to be a very sensitive and specific marker in low-grade fibromyxoid sarcoma,.
# Role in other diseases
MUC-4 is also relevant to several other disease conditions. Polymorphisms in the MUC4 gene have been found to play a role in the progression of endometriosis and related infertility, as well as dysplastic cervical disorders. MUC-4 also has important roles in inflammatory bowel disease such as Crohn's disease and is found to be overexpressed in ulcerative colitis. | Mucin 4
Mucin 4 (MUC 4) is a mucin protein that in humans is encoded by the MUC4 gene.[1] Like other mucins, MUC-4 is a high-molecular weight glycoprotein.[2]
The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues.[3]
MUC-4 has been found to play various roles in the progression of cancer, particularly due to its signaling and anti-adhesive properties which contribute to tumor development and metastasis. It is also found to play roles in other diseases such as endometriosis and inflammatory bowel disease. MUC-4 belongs to the human mucin family that is membrane-anchored and can range in molecular weight from 550 to 930 kDa for the actual protein, and up to 4,650 kDa with glycosylation.[4]
# Structure
MUC-4 is an O-glycoprotein that can reach up to 2 micrometers outside the cell.[4] MUC-4 mucins consist of a large extracellular alpha subunit that is heavily glycosylated and a beta subunit that is anchored in the cell membrane and extends into the cytosol.[5] This beta subunit is considered an oncogene, whose role in cancer is increasingly being recognized particularly due to its involvement in signalling pathways, particularly with ErbB2 (Her2).[5] This subunit serves as a ligand for ErbB2, which is suggested to cause the repression of apoptosis found in many cancer cells.[6]
The large alpha subunit that is glycosylated likely confers the anti-adhesive properties to the cell, allowing for cell–cell and cell–matrix detachment in normal as well as cancerous cells.[4] The heavy glycosylation may also serve as a reservoir for growth factors, which may become released upon degradation.[7]
The two subunits of MUC-4 are transcribed from a single gene.[6] Over 24 splice variants have been found for MUC4, in normal as well as abnormal tissue.[4][8] Some forms are soluble, while others are membrane bound.[6] Many polymorphisms are observed in the tandem repeat region of the alpha subunit, which has a variable number of repeats.[9][10]
# Function
## Normal
In normal functioning, MUC-4 is known to play anti-adhesive roles in the body, such as in lubricating the reproductive lining.[11] It is also found in the respiratory tract - particularly in the trachea and lung - and the digestive tract - in the esophagus and colon - as well as in the visual and auditory systems.[4] In these roles, MUC-4 serves to protect and lubricate the epithelium, which facilitates transport and traps foreign particles. One example of its function in the reproductive lining relates to blastocyst implantation resulting from MUC4 downregulation.[6] It is found to be overexpressed during the luteal phase of menstruation.[12] MUC-4 may also have a role in fetal morphogenic development.[4] It should be noted that MUC-4 is not found in the gallbladder, pancreas, or liver except in abnormal conditions such as cancer. MUC-4, however, may normally be found in bodily fluids like saliva, tears, and milk.[7] In the soluble form, MUC-4 appears to lubricate the epithelial mucosa.[6]
## Disease
MUC-4 is thought to play a role in cancer progression by repressing apoptosis and consequently increasing tumor cell proliferation.[13] The molecular mechanism is thought to be through a MUC-4 complex with ERBB2 receptors, which alters downstream signaling and down regulates CDKN1B.[13] The beta subunit of MUC-4 appears to serve as a ligand that causes the phosphorylation of ErbB2, but does not activate the MAPK or AKT pathways.[14] MUC-4 may also affect HER2 signaling, and result in its stabilization.[4][15] As a mucin, MUC-4 also alters adhesive properties of the cell. When overexpressed, the disorganization of mucins may reduce adhesion to other cells as well as the extracellular matrix, promoting cancer cell migration and metastasis.
# Role in cancer
## Pancreatic
MUC4 is often overexpressed in pancreatic adenocarcinomas and has been shown to promote tumor growth and metastasis, though the mechanism by which it does so is not known.[2] MUC4 detection is emerging as a method to diagnose pancreatic cancer, especially since MUC4 is not detectably expressed in normal pancreas and increased expression of MUC-4 suggests a greater progression of the disease.[2] Scientists have recently experimented with MUC4 inhibition in pancreatic cancer using drug delivery methods such as microRNAs.[16] Such efforts have been successful at reducing EGF receptor expression, its downstream signaling, and consequently malignant behavior of the cancer cell such as migration, invasion, and cell detachment.
## Esophageal
MUC4 expression in esophageal cancer often leads to increased tumor proliferation and migration. Like with prostate cancer, increased expression of MUC4 suggests greater development of esophageal cancer. Bile acids present in gastroesophageal reflux disease are thought to contribute to this over-expression of MUC4. By inhibiting MUC-4, scientists have been able to reduce cancer cell proliferation, migration, and tumor size as well as reduce protein S100A4 expression, presenting MUC-4 as a good therapeutic target for the treatment of esophageal cancer.[17]
## Breast
Unlike pancreatic and esophageal cancers, MUC4 expression is suppressed in the primary tumor when compared to normal cells.[18] It, however, is found to be overexpressed in lymph node metastases. The initial reduction in MUC-4 appears to promote the transition to the primary tumor, but its subsequent increase in expression facilitate metastasis and ultimately increased malignancy[18]
## Other
MUC4 is found to be overexpressed in papillary thyroid carcinoma, and could serve as a potential marker of malignancy and prognosis.[19] MUC-4 is also found to be a very sensitive and specific marker in low-grade fibromyxoid sarcoma,.[20]
# Role in other diseases
MUC-4 is also relevant to several other disease conditions. Polymorphisms in the MUC4 gene have been found to play a role in the progression of endometriosis and related infertility,[11] as well as dysplastic cervical disorders.[21] MUC-4 also has important roles in inflammatory bowel disease such as Crohn's disease and is found to be overexpressed in ulcerative colitis.[22] | https://www.wikidoc.org/index.php/Mucin_4 | |
88cee540b618a5d900f82c610969cbf4927bad06 | wikidoc | Mucin 7 | Mucin 7
Mucin-7 is a protein that in humans is encoded by the MUC7 gene. In animals, the MUC7 gene is found in most placental mammals, but not marsupials.
# Human variations
Humans carry either a five or six tandem repeat version of the gene. In other primates, the number of repeats found is 4-5 for gorillas, 5 for chimpanzees, 6-7 for orangutans, 8-10 for macaques, 10-11 for baboons and 11-12 for green monkeys.
Some modern people from Sub-Saharan Africa were found to carry a five tandem repeat variation of the MUC7 gene that is highly divergent from other, modern humans. The estimated coalescence age for the human variations of the MUC7 gene is estimated to be around 4.5 million years ago, which predates the human-Neanderthal split. Neanderthals and Denisovans also carry variants that are much closer to those of other, modern humans; thus, researcers postulate that this divergent Sub-Saharan variant most likely introgressed from a currently yet-unknown archaic human ghost population. | Mucin 7
Mucin-7 is a protein that in humans is encoded by the MUC7 gene.[1][2] In animals, the MUC7 gene is found in most placental mammals, but not marsupials.[3]
# Human variations
Humans carry either a five or six tandem repeat version of the gene. In other primates, the number of repeats found is 4-5 for gorillas, 5 for chimpanzees, 6-7 for orangutans, 8-10 for macaques, 10-11 for baboons and 11-12 for green monkeys.[3]
Some modern people from Sub-Saharan Africa were found to carry a five tandem repeat variation of the MUC7 gene that is highly divergent from other, modern humans. The estimated coalescence age for the human variations of the MUC7 gene is estimated to be around 4.5 million years ago, which predates the human-Neanderthal split. Neanderthals and Denisovans also carry variants that are much closer to those of other, modern humans; thus, researcers postulate that this divergent Sub-Saharan variant most likely introgressed from a currently yet-unknown archaic human ghost population.[4] | https://www.wikidoc.org/index.php/Mucin_7 | |
552a5a8aef7c76481445f90017c0b20295faee9f | wikidoc | Mullein | Mullein
The Mulleins (Verbascum) are a genus of about 250 species of flowering plants in the figwort family (Scrophulariaceae). They are native to Europe and Asia, with the highest species diversity in the Mediterranean region.
They are biennial or perennial plants, rarely annuals or subshrubs, growing to 0.5-3 m tall. The plants first form a dense rosette of leaves at ground level, subsequently sending up a tall flowering stem. The leaves are spirally arranged, often densely hairy, though glabrous (hairless) in some species. The flowers have five symmetrical petals; petal colours in different species include yellow (most common), orange, red-brown, purple, blue or white. The fruit is a capsule containing numerous minute seeds.
# Cultivation and uses
Various species have been introduced (and in some case naturalised) in the Americas, Australia and Hawaii.
Since the year 2000 a number of new hybrid cultivars have come out that have increased flower size with shorter heights and tend to be longer lived plants. A number have new colors for this genus. Many are raised from seed, both the short lived perennial and biennial types. In the landscape they are valued for their tall narrow stature and for flowering over a long period of time, even in dry soils.
One of the best known species is Verbascum thapsus (Great mullein), which is used as a herbal remedy for sore throat, cough and lung diseases.
Mullein is also the active ingredient in many alternative smoking blends. | Mullein
The Mulleins (Verbascum) are a genus of about 250 species of flowering plants in the figwort family (Scrophulariaceae). They are native to Europe and Asia, with the highest species diversity in the Mediterranean region.
They are biennial or perennial plants, rarely annuals or subshrubs, growing to 0.5-3 m tall. The plants first form a dense rosette of leaves at ground level, subsequently sending up a tall flowering stem. The leaves are spirally arranged, often densely hairy, though glabrous (hairless) in some species. The flowers have five symmetrical petals; petal colours in different species include yellow (most common), orange, red-brown, purple, blue or white. The fruit is a capsule containing numerous minute seeds.
## Cultivation and uses
Various species have been introduced (and in some case naturalised) in the Americas, Australia and Hawaii.
Since the year 2000 a number of new hybrid cultivars have come out that have increased flower size with shorter heights and tend to be longer lived plants. A number have new colors for this genus. Many are raised from seed, both the short lived perennial and biennial types. In the landscape they are valued for their tall narrow stature and for flowering over a long period of time, even in dry soils.
One of the best known species is Verbascum thapsus (Great mullein), which is used as a herbal remedy for sore throat, cough and lung diseases.
Mullein is also the active ingredient in many alternative smoking blends. | https://www.wikidoc.org/index.php/Mullein | |
d58ce319669943096b5049f1a3596e760cd63e6d | wikidoc | Murrain | Murrain
Murrain (Pronounced "mur'in") is a highly infectious disease of cattle and sheep. It literally means "disease" and was used in medieval times to represent just that. The population of that era had no way of identifying specific diseases in their livestock so they simply put all illnesses under one heading. There were major sheep and cattle murrains in Europe during the 14th century, which combined with the Little Ice Age resulted in widespread famine during the Great Famine of 1315-1317, weakening the population of Europe before the onset of the Black Death in 1348.
Murrain is also mentioned once in the Bible relating to the fifth plague brought upon Egypt.
Exodus 9:3: "Behold, the hand of the LORD is upon thy cattle which is in the field, upon the horses, upon the asses, upon the camels, upon the oxen, and upon the sheep: there shall be a very grievous murrain."
In some parts of Scotland, force-fire was believed to cure it. | Murrain
Murrain (Pronounced "mur'in") is a highly infectious disease of cattle and sheep. It literally means "disease" and was used in medieval times to represent just that. The population of that era had no way of identifying specific diseases in their livestock so they simply put all illnesses under one heading[citation needed]. There were major sheep and cattle murrains in Europe during the 14th century, which combined with the Little Ice Age resulted in widespread famine during the Great Famine of 1315-1317, weakening the population of Europe before the onset of the Black Death in 1348.
Murrain is also mentioned once in the Bible relating to the fifth plague brought upon Egypt.
Exodus 9:3: "Behold, the hand of the LORD is upon thy cattle which is in the field, upon the horses, upon the asses, upon the camels, upon the oxen, and upon the sheep: there shall be a very grievous murrain."
In some parts of Scotland, force-fire was believed to cure it.
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Murrain | |
7cd65231e2f2fe4193aae17fdf74b2d0ffae47a6 | wikidoc | Mutagen | Mutagen
In biology, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogens. Not all mutations are caused by mutagens: So-called "spontaneous mutations" occur due to errors in DNA replication, repair and recombination of DNA sequences.
# Effects of mutations
The changes in nucleic acid sequences by mutations include substitution of nucleotide base-pairs and insertions and deletions of one or more nucleotides in DNA sequences. Although many of these mutations are lethal, or cause serious disease, some have minor effects, as the changes they cause in the sequence of encoded proteins are not significant. Many mutations cause no visible effects at all, either because they occur in introns, or because they do not change the amino-acid sequence, due to redundancy of codons.
# Genetic drift
The change in a population’s genetic material due to the accumulation of random chance is called drift and serves as a molecular clock. In general, the more nucleotide differences between two organisms, the more time has elapsed since their last common ancestor. Though it is difficult to determine in many organisms, estimates for mutation rates have been made for both E. coli and eukaryotes. It was estimated that in these organisms about one nucleotide in every 1010 is changed and continues through reproduction to future generations of cells.
# Discovery of mutagenesis
In the 1920s, Hermann Muller discovered that x-rays caused mutations in fruit flies. He went on to use x-rays to create Drosophila mutants that he used in his studies of genetics. He also discovered that x-rays did not only mutate genes in fruit flies, but also had effects on the genetic makeup of humans.
# Nature of mutagens
Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:
- Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of the substrates.
- Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
- Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.
The Ames test is one method to determine how mutagenic an agent is.
# Examples
- Nitrous acid, (HNO2) Deaminating agent
- UV Radiation, thymine dimer formation
- Sodium azide, (NaN3)
- Gamma and Alpha Radiation, ionising radiations
- Transposons, autonomous DNA fragment relocation/multiplication
- Base analogues, substitutes
- Bromine and some of its compounds,
- Ethidium bromide (EtBr), and other intercalating agents.
- Bromouracil,Alkylating Agent
- Vinca Alkaloids, Natural Plant Alkaloid
# Mutagens in fiction
In science fiction, mutagens are often represented as substances that are capable of completely changing the form of the recipient.
- The Inhumans of Marvel Comics utilize a mutagen called the "Terrigen Mist".
- The Teenage Mutant Ninja Turtles were supposedly created by means of mutagens, as well as their master Splinter and (in the 1987 cartoon) their enemies Bebop and Rocksteady.
- In the Street Fighter movie, a bag of mutagens is used by General Bison to transform Carlos Blanka into a monster.
- In Lego's Bionicle franchise, the water surrounding the pit is mutagenic, causing mutation in most of the major characters who enter the water. | Mutagen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In biology, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogens. Not all mutations are caused by mutagens: So-called "spontaneous mutations" occur due to errors in DNA replication, repair and recombination of DNA sequences.
# Effects of mutations
The changes in nucleic acid sequences by mutations include substitution of nucleotide base-pairs and insertions and deletions of one or more nucleotides in DNA sequences. Although many of these mutations are lethal, or cause serious disease, some have minor effects, as the changes they cause in the sequence of encoded proteins are not significant. Many mutations cause no visible effects at all, either because they occur in introns, or because they do not change the amino-acid sequence, due to redundancy of codons.
# Genetic drift
The change in a population’s genetic material due to the accumulation of random chance is called drift and serves as a molecular clock. In general, the more nucleotide differences between two organisms, the more time has elapsed since their last common ancestor. Though it is difficult to determine in many organisms, estimates for mutation rates have been made for both E. coli and eukaryotes. It was estimated that in these organisms about one nucleotide in every 1010 is changed and continues through reproduction to future generations of cells.
# Discovery of mutagenesis
In the 1920s, Hermann Muller discovered that x-rays caused mutations in fruit flies. He went on to use x-rays to create Drosophila mutants that he used in his studies of genetics. He also discovered that x-rays did not only mutate genes in fruit flies, but also had effects on the genetic makeup of humans.[1]
# Nature of mutagens
Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:
- Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of the substrates.
- Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
- Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.
The Ames test is one method to determine how mutagenic an agent is.
# Examples
- Nitrous acid, (HNO2) Deaminating agent
- UV Radiation, thymine dimer formation
- Sodium azide, (NaN3)
- Gamma and Alpha Radiation, ionising radiations
- Transposons, autonomous DNA fragment relocation/multiplication
- Base analogues, substitutes
- Bromine and some of its compounds,
- Ethidium bromide (EtBr), and other intercalating agents.
- Bromouracil,Alkylating Agent
- Vinca Alkaloids, Natural Plant Alkaloid
# Mutagens in fiction
In science fiction, mutagens are often represented as substances that are capable of completely changing the form of the recipient.
- The Inhumans of Marvel Comics utilize a mutagen called the "Terrigen Mist".
- The Teenage Mutant Ninja Turtles were supposedly created by means of mutagens, as well as their master Splinter and (in the 1987 cartoon) their enemies Bebop and Rocksteady.
- In the Street Fighter movie, a bag of mutagens is used by General Bison to transform Carlos Blanka into a monster.
- In Lego's Bionicle franchise, the water surrounding the pit is mutagenic, causing mutation in most of the major characters who enter the water. | https://www.wikidoc.org/index.php/Mutagen | |
dfd41a429deb9be7e573796a45c8faa7f2b3a19d | wikidoc | Myiasis | Myiasis
# Overview
Myiasis is an animal or human disease caused by parasitic dipterous fly larvae feeding on the host's necrotic or living tissue. Colloquialisms for Myiasis include "fly-strike" and "fly-blown".
Blowfly strike, known as myiasis, is a common disease in sheep, especially in areas where there are hot and wet conditions. The female flies lay their eggs on the sheep in damp, protected areas soiled with urine and faeces, mainly on the breech. It takes approximately 8 hours to a day for the eggs to hatch, depending on the conditions. This results in sores as the larvae lacerate the skin and this is the primary reason for the early removal of lambs' tails. The larvae then tunnel into the host's tissue causing irritating lesions. After about the second day bacterial infection occurs and if left untreated causes toxemia or septicemia. This leads to anorexia and weakness and if untreated will lead to death. Blowfly strike accounts for over $170 million a year in losses in the Australian sheep industry and so prevention measures such as mulesing are practiced.
German entomologist Fritz Zumpt describes myiasis as "the infestation of live human and vertebrate animals with dipterous larvae, which at least for a period, feed on the host's dead or living tissue, liquid body substances, or ingested food."
# Classifications
Two different classifications of myiasis can be adopted:
- The classical classification describes the myiasis by the infected area of the host. This is the classification used by ICD-10. For example: dermal, sub-dermal, cutaneous (B87.0), nasopharyngeal (B87.3), ocular (B87.2), intestinal/enteric (B87.8), or urogenital (B87.8).
- Another classification is based on the relationship between the host and the parasite and provides insight into the biology of the fly species causing the myiasis and its likely effect. Thus the myiasis is described as either obligatory or facultative or accidental.
# Flies responsible for Myiasis
There are three main fly families causing economically important myiasis in livestock and also, occasionally, in humans:
- Oestroidea (botflies)
- Calliphoridae (blowflies)
- Sarcophagidae (fleshflies)
Other families occasionally involved are:
- Anisopodidae
- Piophilidae
- Stratiomyidae
- Syrphidae
The adult flies are not parasitic, but when they lay their eggs in open wounds and these hatch into their larval stage (also known as maggots or grubs), the larvae feed on live and/or necrotic tissue, causing myiasis to develop. They may also be ingested or enter through other body apertures.
# Physical examination
## Gallery
### Skin
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# Control methods
The first control method is preventive and aims to eradicate the adult flies before they can cause any damage and is called vector control. The second control method is the treatment once the infestation is present, and concerns the infected animals (or humans).
## Prevention
The principal control method of adult populations of myiasis inducing flies involves insecticide applications in the environment where the target livestock is kept. Organophosphorus or organochlorine compounds may be used, usually in a spraying formulation. One alternative prevention method is the SIT (Sterile Insect Technique) where a significant number of artificially reared sterilized (usually through irradiation) male flies are introduced. The male flies compete with wild bred males for females in order to copulate and thus cause females to lay batches of unfertilised eggs which can't develop into the larval stage.
Another prevention method involves removing the environment most favourable to the flies. One example of this is the crutching of sheep, which involves the removal of wool from around the tail and between the rear legs, which is a favourable environment for the larvae. Another more permanent practice which is used in some countries is mulesing, where skin is removed from young animals to tighten remaining skin - leaving it less prone to fly attack. PETA have been campaigning to have farmers cease mulesing. Celebrities such as Pink, Toni Collette and Chrissie Hynde have also participated in PETA's campaign against the mulesing practice; Collette has since changed her stance, however.
## Treatment
This applies once an infection is underway. First the larvae must be eliminated through pressure around the lesion and the use of forceps. Secondly the wound must be cleaned and disinfected. Further control is necessary to avoid further reinfection.
It is also possible to treat livestock with the use of slow release boluses containing ivermectin which can provide long term protection against the larvae development.
Sheep may be dipped, which involves drenching the sheep in insecticide to prevent the growth of the larvae.
### Antimicrobial Regimen
- Myiasis
- Preferred regimen: No medications approved by the FDA are available for treatment
- Note: Fly larvae need to be surgically removed.
# Use of Myiasitic maggots in medicine
Through the ages maggots have been used in medicine in order to clean out necrotic wounds. For more information, see Maggot therapy.
Maggot Therapy (also known as Maggot Debridement Therapy (MDT), larval therapy, larva therapy, or larvae therapy), is the intentional introduction by a health care practitioner of live, disinfected green bottle fly maggots or larvae into the non-healing skin and soft tissue wound(s) of a human or other animal for the purpose of selectively cleaning out only the necrotic (dead) tissue within a wound in order to promote wound healing.
The larvae of the green bottle fly (a type of blow-fly) are now used exclusively for this purpose, since they preferentially devour only necrotic tissue, leaving healthy tissue intact. This is an important distinction, as most other major varieties of myiasitic fly larvae attack both live and dead wound tissue indiscriminately, effectively negating their benefit in non-harmful wound debridement. | Myiasis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2].
# Overview
Myiasis is an animal or human disease caused by parasitic dipterous fly larvae feeding on the host's necrotic or living tissue. Colloquialisms for Myiasis include "fly-strike" and "fly-blown".
Blowfly strike, known as myiasis, is a common disease in sheep, especially in areas where there are hot and wet conditions. The female flies lay their eggs on the sheep in damp, protected areas soiled with urine and faeces, mainly on the breech. It takes approximately 8 hours to a day for the eggs to hatch, depending on the conditions. This results in sores as the larvae lacerate the skin and this is the primary reason for the early removal of lambs' tails. The larvae then tunnel into the host's tissue causing irritating lesions. After about the second day bacterial infection occurs and if left untreated causes toxemia or septicemia. This leads to anorexia and weakness and if untreated will lead to death. Blowfly strike accounts for over $170 million a year in losses in the Australian sheep industry and so prevention measures such as mulesing are practiced.
German entomologist Fritz Zumpt describes myiasis as "the infestation of live human and vertebrate animals with dipterous larvae, which at least for a period, feed on the host's dead or living tissue, liquid body substances, or ingested food."
# Classifications
Two different classifications of myiasis can be adopted:
- The classical classification describes the myiasis by the infected area of the host. This is the classification used by ICD-10. For example: dermal, sub-dermal, cutaneous (B87.0), nasopharyngeal (B87.3), ocular (B87.2), intestinal/enteric (B87.8), or urogenital (B87.8).
- Another classification is based on the relationship between the host and the parasite and provides insight into the biology of the fly species causing the myiasis and its likely effect. Thus the myiasis is described as either obligatory or facultative or accidental.
# Flies responsible for Myiasis
There are three main fly families causing economically important myiasis in livestock and also, occasionally, in humans:
- Oestroidea (botflies)
- Calliphoridae (blowflies)
- Sarcophagidae (fleshflies)
Other families occasionally involved are:
- Anisopodidae
- Piophilidae
- Stratiomyidae
- Syrphidae
The adult flies are not parasitic, but when they lay their eggs in open wounds and these hatch into their larval stage (also known as maggots or grubs), the larvae feed on live and/or necrotic tissue, causing myiasis to develop. They may also be ingested or enter through other body apertures.
# Physical examination
## Gallery
### Skin
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=310>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=310>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=310>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=311>
# Control methods
The first control method is preventive and aims to eradicate the adult flies before they can cause any damage and is called vector control. The second control method is the treatment once the infestation is present, and concerns the infected animals (or humans).
## Prevention
The principal control method of adult populations of myiasis inducing flies involves insecticide applications in the environment where the target livestock is kept. Organophosphorus or organochlorine compounds may be used, usually in a spraying formulation. One alternative prevention method is the SIT (Sterile Insect Technique) where a significant number of artificially reared sterilized (usually through irradiation) male flies are introduced. The male flies compete with wild bred males for females in order to copulate and thus cause females to lay batches of unfertilised eggs which can't develop into the larval stage.
Another prevention method involves removing the environment most favourable to the flies. One example of this is the crutching of sheep, which involves the removal of wool from around the tail and between the rear legs, which is a favourable environment for the larvae. Another more permanent practice which is used in some countries is mulesing, where skin is removed from young animals to tighten remaining skin - leaving it less prone to fly attack.[1] PETA have been campaigning to have farmers cease mulesing. Celebrities such as Pink, Toni Collette and Chrissie Hynde have also participated in PETA's campaign against the mulesing practice[2]; Collette has since changed her stance, however.[3]
## Treatment
This applies once an infection is underway. First the larvae must be eliminated through pressure around the lesion and the use of forceps. Secondly the wound must be cleaned and disinfected. Further control is necessary to avoid further reinfection.
It is also possible to treat livestock with the use of slow release boluses containing ivermectin which can provide long term protection against the larvae development.
Sheep may be dipped, which involves drenching the sheep in insecticide to prevent the growth of the larvae.
### Antimicrobial Regimen
- Myiasis
- Preferred regimen: No medications approved by the FDA are available for treatment[4]
- Note: Fly larvae need to be surgically removed.
# Use of Myiasitic maggots in medicine
Through the ages maggots have been used in medicine in order to clean out necrotic wounds. For more information, see Maggot therapy.
Maggot Therapy (also known as Maggot Debridement Therapy (MDT), larval therapy, larva therapy, or larvae therapy), is the intentional introduction by a health care practitioner of live, disinfected green bottle fly maggots or larvae into the non-healing skin and soft tissue wound(s) of a human or other animal for the purpose of selectively cleaning out only the necrotic (dead) tissue within a wound in order to promote wound healing.
The larvae of the green bottle fly (a type of blow-fly) are now used exclusively for this purpose, since they preferentially devour only necrotic tissue, leaving healthy tissue intact. This is an important distinction, as most other major varieties of myiasitic fly larvae attack both live and dead wound tissue indiscriminately, effectively negating their benefit in non-harmful wound debridement. | https://www.wikidoc.org/index.php/Myiasis | |
17ba558d0aa27cdac0e913b5583842932c94c281 | wikidoc | Sarcoma | Sarcoma
# Overview
A sarcoma (from the Greek 'sarx' meaning "flesh") is a cancer of the connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue. This is in contrast to carcinomas, which are of epithelial origin (breast, colon, pancreas, and others). It can be classified based on the tissue involved and the histology of the lesion. Soft tissue sarcoma needs to differentiated from soft tissue benign tumors such as Adenoma, lipoma, and fibroma. The estimated incidence of soft tissue sarcoma worldwide is 1.8 to 5 per 100,000 per year. Soft tissue sarcomas are more commonly found in older patients (>50 years old). Risk factors include radiation exposure, damaged lymphatic system, and inherited conditions. There is insufficient evidence to recommend routine screening for sarcoma. If left untreated, sarcoma can lead to complications of local tissue erosion, compression and invasion. Complications can also include side effects of chemotherapy and radiation therapy. Prognosis depends upon the size and stage of the tumor, age and general health of the patient, and benign/malignant nature of the tumor. Sarcoma can be diagnosed by combination of imaging and biopsy. Symptoms include painless swelling or lump, menstrual irregularities, constipation, and indigestion. Chemotherapy may be used with radiation therapy either before or after surgery to try to shrink the tumor or kill any remaining cancer cells. Surgery is the most common treatment for soft tissue sarcomas. It is important to obtain a margin free of tumor to decrease the likelihood of local recurrence and give the best chance for eradication of the tumor. Radiation therapy (treatment with x-rays or radioactive implants) may be used either before surgery to shrink tumors or after surgery to kill any cancer cells that may have been left behind. There are no established measures for the primary and secondary prevention of sarcoma.
# Classification
- Sarcomas are given a number of different names, based on the type of tissue from which they arise. For example, osteosarcoma arises from bone, chondrosarcoma arises from cartilage, and leiomyosarcoma arises from smooth muscle.
- Sarcomas strike people in all age ranges, but they are very rare, accounting for only 1% of all cases of cancer.
- Soft tissue sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children.
- GIST is the most common form of sarcoma, with approximately 3000 - 3500 cases per year in the United States.
- Bone sarcomas, such as osteosarcoma and Ewing's sarcoma, are more common in children than in adults. These tumors most commonly strike adolescents and young adults between the ages of 12 and 25.
- In addition to being named based on the tissue of origin, sarcomas are also assigned a grade, such as low grade or high grade.
- Low grade sarcomas are usually treated surgically, although sometimes radiation therapy or chemotherapy are used.
- High grade sarcomas are more frequently treated with chemotherapy. Since these tumors are more likely to undergo metastasis (spreading to distant sites), these tumors are treated more aggressively.
- Childhood sarcomas are almost always treated with a combination of surgery and chemotherapy, and radiation is frequently used as well.
- The recognition that childhood sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long term survival for patients with localized osteosarcoma was only approximately 20%, but now, it has risen to 60 - 70%.
## Tables
## Types of sarcoma
(ICD-O codes are provided where available.)
- Askin's tumor (8803/3)
- Chondrosarcoma (9220/3-9240/3)
- Ewing's (9260/3) - PNET (9473/3)
- Malignant Hemangioendothelioma (9130/3)
- Malignant Schwannoma (9560/3-9561/3)
- Osteosarcoma (9180/3-9190/3)
- Soft tissue sarcomas, including:
Alveolar soft part sarcoma (9581/3)
Angiosarcoma (9120/3)
Cystosarcoma Phylloides
Dermatofibrosarcoma (8832/3-8833/3)
Desmoid Tumor (8821/1-8822/1)
Desmoplastic small round cell tumor (8806/3)
Epithelioid Sarcoma (8804/3)
Extraskeletal chondrosarcoma (9220/3)
Extraskeletal osteosarcoma (9180/3)
Fibrosarcoma (8810/3)
Hemangiopericytoma (9150)
Hemangiosarcoma (9120/3)
Kaposi's sarcoma (9140/3)
Leiomyosarcoma (8890/3-8896/3)
Liposarcoma (8850/3-8858/3)
Lymphangiosarcoma (9170-9175)
Lymphosarcoma
Malignant fibrous histiocytoma (8830/3)
Neurofibrosarcoma (9540/3)
Rhabdomyosarcoma (8900-8920)
Synovial sarcoma (9040/3-9043/3)
- Alveolar soft part sarcoma (9581/3)
- Angiosarcoma (9120/3)
- Cystosarcoma Phylloides
- Dermatofibrosarcoma (8832/3-8833/3)
- Desmoid Tumor (8821/1-8822/1)
- Desmoplastic small round cell tumor (8806/3)
- Epithelioid Sarcoma (8804/3)
- Extraskeletal chondrosarcoma (9220/3)
- Extraskeletal osteosarcoma (9180/3)
- Fibrosarcoma (8810/3)
- Hemangiopericytoma (9150)
- Hemangiosarcoma (9120/3)
- Kaposi's sarcoma (9140/3)
- Leiomyosarcoma (8890/3-8896/3)
- Liposarcoma (8850/3-8858/3)
- Lymphangiosarcoma (9170-9175)
- Lymphosarcoma
- Malignant fibrous histiocytoma (8830/3)
- Neurofibrosarcoma (9540/3)
- Rhabdomyosarcoma (8900-8920)
- Synovial sarcoma (9040/3-9043/3)
# Differentiating Sarcoma from Other Diseases
Soft tissue sarcoma needs to differentiated from soft tissue benign tumors such as:
- Adenoma
- Lipoma
- Fibroma
# Epidemiology and Demographics
## Incidence
- The estimated number of new cases of soft tissue sarcoma in the United States is approximately 12,000.
- The estimated incidence of soft tissue sarcoma worldwide is 1.8 to 5 per 100,000 per year.
## Age
- Soft tissue sarcomas are more commonly found in older patients (>50 years old).
- Certain histological sub-types are more common in children and adolescents under age 20 (rhabdomyosarcoma).
## Percent Distribution of Soft Tissue Sarcoma by Histology
- Fibrosarcoma: 6.9%
- Infantile fibrosarcoma: 0.2%
- Fibrous histiocytoma, malignant: 9.2%
- Dermatofibrosarcoma: 3.6%
- Liposarcoma: 17.1%
- Leiomyosarcoma: 13.2%
- Rhabdomyosarcoma: 3.1%
- Embryonal rhabdomyosarcoma: 1.3%
- Hemangiosarcoma: 3.7%
- Hemangiopericytoma, malignant: 0.5%
- Kaposi's sarcoma: 0.8%
- Malignant peripheral nerve sheath tumor: 1.6%
- Malignant neurilemmoma: 0.2%
- Neuroblastoma: 0.6%
- Synovial sarcoma: 4.8%
# Risk Factors
- Radiation exposure: Clinical studies suggest that patients with other kind of cancers such as lymphoma and breast cancer may develop sarcomas from radiation therapy. The sarcoma often develops in the area of the body that had been treated with radiation.
- Damaged lymphatic system: Clinical observations demonstrate that lymphangiosarcoma is a very rare complication of chronic lymphedema that is the result of damaged lymphatic system.
- Inherited conditions: Some inherited conditions may increase the risk of developing soft tissue sarcomas, such as neurofibromatosis, Gardner syndrome, Li-Fraumeni syndrome, Retinoblastoma, and Werner syndrome.
# Screening
- There is insufficient evidence to recommend routine screening for sarcoma.
# Natural History, Complications, and Prognosis
- If left untreated, sarcoma can lead to complications of local tissue erosion, compression and invasion.
- It can also lead to metastasis to distant sites.
- Complications can also include side effects of chemotherapy and radiation therapy.
- Surgical wound after resection can also complicate a sarcoma.
- The prognosis of soft tissue sarcoma is poor and it depends on the following:
- Whether or not the tumor can be removed by surgery
- The stage of the sarcoma:
The size of the tumor.
Benign or malignant nature.
- The size of the tumor.
- Benign or malignant nature.
- The patient’s general health.
- Whether the sarcoma has just been diagnosed or has recurred.
# Diagnosis
## Diagnostic Study of Choice
- Sarcoma can be diagnosed by combination of imaging and biopsy.
## History and Symptoms
- Painless lump or swelling
- Pain or soreness
- Menstrual cramps
- Indigestion
- Constipation
## Physical Examination
- Patients with sarcoma usually appear normal.
- Common physical examination findings include painless lump or swelling.
## Laboratory Findings
- There are no diagnostic laboratory findings associated with sarcoma.
## Electrocardiogram
- There are no ECG findings associated with sarcoma.
## X-ray
- X-ray can be the first investigation ordered to evaluate a suspected sarcoma.
- Chest x-ray can help rule in/out metastasis to the lungs.
## Echocardiography or Ultrasound
- Ultrasound can help determine if a suspected sarcoma is fluid filled.
- Ultrasound is usually performed before biopsy.
## CT scan
- CT scan can be used as a guiding tool in taking biopsy.
- It can also help in making a diagnosis of the lesion itself.
## MRI
- MRI determines the extent of tumor invasion.
- It provides a detailed picture of the lesion.
- It can also help in determining the tissue of origin.
## Other Imaging Findings
- PET (positron emission tomography) scan can be used to determine the spread of sarcoma.
## Other Diagnostic Studies
- There are no other diagnostic studies associated with sarcoma.
# Treatment
## Medical Therapy
- Chemotherapy may be used with radiation therapy either before or after surgery to try to shrink the tumor or kill any remaining cancer cells.
- In general, the effects of chemotherapy on soft tissue sarcoma have had little impact as opposed to other cancers.
- If the cancer has spread to other areas of the body, chemotherapy may be used to shrink tumors and reduce the pain and discomfort.
- The use of chemotherapy to prevent the spread of soft tissue sarcomas has not been proven to be effective.
- Patients with soft tissue sarcomas usually receive chemotherapy intravenously.
## Surgery
- Surgery is the most common treatment for soft tissue sarcomas.
- Depending on the size and location of the sarcoma, it may occasionally be necessary to remove all or part of an arm or leg (amputation).
- In most cases, limb-sparing surgery is an option to avoid amputating the arm or leg.
- It is important to obtain a margin free of tumor to decrease the likelihood of local recurrence and give the best chance for eradication of the tumor.
## Radiation Therapy
- Radiation therapy (treatment with x-rays or radioactive implants) may be used either before surgery to shrink tumors or after surgery to kill any cancer cells that may have been left behind.
- In some cases, it can be used to treat tumors that cannot be surgically removed.
- In multiple studies, radiation therapy has been found to improve the rate of local control, but has not had any influence on overall survival.
## Primary Prevention
- There are no established measures for the primary prevention of sarcoma.
## Secondary Prevention
- There are no established measures for the secondary prevention of sarcoma. | Sarcoma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Sabawoon Mirwais, M.B.B.S, M.D.[2]
# Overview
A sarcoma (from the Greek 'sarx' meaning "flesh") is a cancer of the connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue. This is in contrast to carcinomas, which are of epithelial origin (breast, colon, pancreas, and others). It can be classified based on the tissue involved and the histology of the lesion. Soft tissue sarcoma needs to differentiated from soft tissue benign tumors such as Adenoma, lipoma, and fibroma. The estimated incidence of soft tissue sarcoma worldwide is 1.8 to 5 per 100,000 per year. Soft tissue sarcomas are more commonly found in older patients (>50 years old). Risk factors include radiation exposure, damaged lymphatic system, and inherited conditions. There is insufficient evidence to recommend routine screening for sarcoma. If left untreated, sarcoma can lead to complications of local tissue erosion, compression and invasion. Complications can also include side effects of chemotherapy and radiation therapy. Prognosis depends upon the size and stage of the tumor, age and general health of the patient, and benign/malignant nature of the tumor. Sarcoma can be diagnosed by combination of imaging and biopsy. Symptoms include painless swelling or lump, menstrual irregularities, constipation, and indigestion. Chemotherapy may be used with radiation therapy either before or after surgery to try to shrink the tumor or kill any remaining cancer cells. Surgery is the most common treatment for soft tissue sarcomas. It is important to obtain a margin free of tumor to decrease the likelihood of local recurrence and give the best chance for eradication of the tumor. Radiation therapy (treatment with x-rays or radioactive implants) may be used either before surgery to shrink tumors or after surgery to kill any cancer cells that may have been left behind. There are no established measures for the primary and secondary prevention of sarcoma.
# Classification
- Sarcomas are given a number of different names, based on the type of tissue from which they arise. For example, osteosarcoma arises from bone, chondrosarcoma arises from cartilage, and leiomyosarcoma arises from smooth muscle.
- Sarcomas strike people in all age ranges, but they are very rare, accounting for only 1% of all cases of cancer.[1]
- Soft tissue sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children.
- GIST is the most common form of sarcoma, with approximately 3000 - 3500 cases per year in the United States.[2]
- Bone sarcomas, such as osteosarcoma and Ewing's sarcoma, are more common in children than in adults. These tumors most commonly strike adolescents and young adults between the ages of 12 and 25.
- In addition to being named based on the tissue of origin, sarcomas are also assigned a grade, such as low grade or high grade.
- Low grade sarcomas are usually treated surgically, although sometimes radiation therapy or chemotherapy are used.
- High grade sarcomas are more frequently treated with chemotherapy. Since these tumors are more likely to undergo metastasis (spreading to distant sites), these tumors are treated more aggressively.
- Childhood sarcomas are almost always treated with a combination of surgery and chemotherapy, and radiation is frequently used as well.
- The recognition that childhood sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long term survival for patients with localized osteosarcoma was only approximately 20%, but now, it has risen to 60 - 70%.[3]
## Tables
## Types of sarcoma
(ICD-O codes are provided where available.)
- Askin's tumor (8803/3)
- Chondrosarcoma (9220/3-9240/3)
- Ewing's (9260/3) - PNET (9473/3)
- Malignant Hemangioendothelioma (9130/3)
- Malignant Schwannoma (9560/3-9561/3)
- Osteosarcoma (9180/3-9190/3)
- Soft tissue sarcomas, including:
Alveolar soft part sarcoma (9581/3)
Angiosarcoma (9120/3)
Cystosarcoma Phylloides[3]
Dermatofibrosarcoma (8832/3-8833/3)
Desmoid Tumor (8821/1-8822/1)
Desmoplastic small round cell tumor (8806/3)
Epithelioid Sarcoma (8804/3)
Extraskeletal chondrosarcoma (9220/3)
Extraskeletal osteosarcoma (9180/3)
Fibrosarcoma (8810/3)
Hemangiopericytoma (9150)
Hemangiosarcoma (9120/3)
Kaposi's sarcoma (9140/3)
Leiomyosarcoma (8890/3-8896/3)
Liposarcoma (8850/3-8858/3)
Lymphangiosarcoma (9170-9175)
Lymphosarcoma
Malignant fibrous histiocytoma (8830/3)
Neurofibrosarcoma (9540/3)
Rhabdomyosarcoma (8900-8920)
Synovial sarcoma (9040/3-9043/3)
- Alveolar soft part sarcoma (9581/3)
- Angiosarcoma (9120/3)
- Cystosarcoma Phylloides[3]
- Dermatofibrosarcoma (8832/3-8833/3)
- Desmoid Tumor (8821/1-8822/1)
- Desmoplastic small round cell tumor (8806/3)
- Epithelioid Sarcoma (8804/3)
- Extraskeletal chondrosarcoma (9220/3)
- Extraskeletal osteosarcoma (9180/3)
- Fibrosarcoma (8810/3)
- Hemangiopericytoma (9150)
- Hemangiosarcoma (9120/3)
- Kaposi's sarcoma (9140/3)
- Leiomyosarcoma (8890/3-8896/3)
- Liposarcoma (8850/3-8858/3)
- Lymphangiosarcoma (9170-9175)
- Lymphosarcoma
- Malignant fibrous histiocytoma (8830/3)
- Neurofibrosarcoma (9540/3)
- Rhabdomyosarcoma (8900-8920)
- Synovial sarcoma (9040/3-9043/3)
# Differentiating Sarcoma from Other Diseases
Soft tissue sarcoma needs to differentiated from soft tissue benign tumors such as:
- Adenoma
- Lipoma
- Fibroma
# Epidemiology and Demographics
## Incidence
- The estimated number of new cases of soft tissue sarcoma in the United States is approximately 12,000.[4]
- The estimated incidence of soft tissue sarcoma worldwide is 1.8 to 5 per 100,000 per year.[5]
## Age
- Soft tissue sarcomas are more commonly found in older patients (>50 years old).
- Certain histological sub-types are more common in children and adolescents under age 20 (rhabdomyosarcoma).
## Percent Distribution of Soft Tissue Sarcoma by Histology
- Fibrosarcoma: 6.9%
- Infantile fibrosarcoma: 0.2%
- Fibrous histiocytoma, malignant: 9.2%
- Dermatofibrosarcoma: 3.6%
- Liposarcoma: 17.1%
- Leiomyosarcoma: 13.2%
- Rhabdomyosarcoma: 3.1%
- Embryonal rhabdomyosarcoma: 1.3%
- Hemangiosarcoma: 3.7%
- Hemangiopericytoma, malignant: 0.5%
- Kaposi's sarcoma: 0.8%
- Malignant peripheral nerve sheath tumor: 1.6%
- Malignant neurilemmoma: 0.2%
- Neuroblastoma: 0.6%
- Synovial sarcoma: 4.8%
# Risk Factors
- Radiation exposure: Clinical studies suggest that patients with other kind of cancers such as lymphoma and breast cancer may develop sarcomas from radiation therapy. The sarcoma often develops in the area of the body that had been treated with radiation.
- Damaged lymphatic system: Clinical observations demonstrate that lymphangiosarcoma is a very rare complication of chronic lymphedema that is the result of damaged lymphatic system.
- Inherited conditions: Some inherited conditions may increase the risk of developing soft tissue sarcomas, such as neurofibromatosis, Gardner syndrome, Li-Fraumeni syndrome, Retinoblastoma, and Werner syndrome.
# Screening
- There is insufficient evidence to recommend routine screening for sarcoma.
# Natural History, Complications, and Prognosis
- If left untreated, sarcoma can lead to complications of local tissue erosion, compression and invasion.
- It can also lead to metastasis to distant sites.
- Complications can also include side effects of chemotherapy and radiation therapy.
- Surgical wound after resection can also complicate a sarcoma.
- The prognosis of soft tissue sarcoma is poor and it depends on the following:
- Whether or not the tumor can be removed by surgery
- The stage of the sarcoma:
The size of the tumor.
Benign or malignant nature.
- The size of the tumor.
- Benign or malignant nature.
- The patient’s general health.
- Whether the sarcoma has just been diagnosed or has recurred.
# Diagnosis
## Diagnostic Study of Choice
- Sarcoma can be diagnosed by combination of imaging and biopsy.
## History and Symptoms
- Painless lump or swelling
- Pain or soreness
- Menstrual cramps
- Indigestion
- Constipation
## Physical Examination
- Patients with sarcoma usually appear normal.
- Common physical examination findings include painless lump or swelling.
## Laboratory Findings
- There are no diagnostic laboratory findings associated with sarcoma.
## Electrocardiogram
- There are no ECG findings associated with sarcoma.
## X-ray
- X-ray can be the first investigation ordered to evaluate a suspected sarcoma.[6]
- Chest x-ray can help rule in/out metastasis to the lungs.[6]
## Echocardiography or Ultrasound
- Ultrasound can help determine if a suspected sarcoma is fluid filled.[6]
- Ultrasound is usually performed before biopsy.
## CT scan
- CT scan can be used as a guiding tool in taking biopsy.[6]
- It can also help in making a diagnosis of the lesion itself.
## MRI
- MRI determines the extent of tumor invasion.[6]
- It provides a detailed picture of the lesion.[6]
- It can also help in determining the tissue of origin.
## Other Imaging Findings
- PET (positron emission tomography) scan can be used to determine the spread of sarcoma.
## Other Diagnostic Studies
- There are no other diagnostic studies associated with sarcoma.
# Treatment
## Medical Therapy
- Chemotherapy may be used with radiation therapy either before or after surgery to try to shrink the tumor or kill any remaining cancer cells.
- In general, the effects of chemotherapy on soft tissue sarcoma have had little impact as opposed to other cancers.
- If the cancer has spread to other areas of the body, chemotherapy may be used to shrink tumors and reduce the pain and discomfort.
- The use of chemotherapy to prevent the spread of soft tissue sarcomas has not been proven to be effective.
- Patients with soft tissue sarcomas usually receive chemotherapy intravenously.
## Surgery
- Surgery is the most common treatment for soft tissue sarcomas.
- Depending on the size and location of the sarcoma, it may occasionally be necessary to remove all or part of an arm or leg (amputation).
- In most cases, limb-sparing surgery is an option to avoid amputating the arm or leg.
- It is important to obtain a margin free of tumor to decrease the likelihood of local recurrence and give the best chance for eradication of the tumor.
## Radiation Therapy
- Radiation therapy (treatment with x-rays or radioactive implants) may be used either before surgery to shrink tumors or after surgery to kill any cancer cells that may have been left behind.
- In some cases, it can be used to treat tumors that cannot be surgically removed.
- In multiple studies, radiation therapy has been found to improve the rate of local control, but has not had any influence on overall survival.
## Primary Prevention
- There are no established measures for the primary prevention of sarcoma.
## Secondary Prevention
- There are no established measures for the secondary prevention of sarcoma. | https://www.wikidoc.org/index.php/Myosarcoma | |
9cdf22080d17e1dd8c4a27dae0676cacf5664b2a | wikidoc | NAV-CO2 | NAV-CO2
Non-flammable Alcohol Vapor in Carbon Dioxide (NAV-CO2) systems were developed in Japan in the 1990s to sanitize hospitals and ambulances. These systems were developed to respond to a need for a safe, effective, and environmentally sound way to sanitizing without the use of toxic or corrosive chemicals.
# Theory of operation
NAV-CO2 systems use liquid CO2 as a propellant. NAV-CO2 systems combine Alcohol-based sanitizing solutions with a heated stream of CO2 liquid to create a vapor capable of penetrating small crevices and gaps. As CO2 and atomized Alcohol evaporate completely at room temperature, no residue remains. CO2 displaces oxygen, eliminating one of the elements needed to support combustion. Sanitizing chemicals such as quaternary ammonium can be added to alcohol based sanitizers to extend the killing time on surfaces. NAV-CO2 systems are used to sanitize contact surfaces where individuals may become infected. Hand washing and sanitizing surfaces with Alcohol-based solutions are effective methods for the prevention of nosocomial infection.
# Application
Hospitals, Ambulances, Nursing Homes, Public Waiting Areas and Food Processing Plants are likely places where disease causing bacteria and viruses are known to colonize. NAV-CO2 eliminates the use and disposal of toxic chemicals such as bleach and other commercial products.
# Effectiveness against Pathogens
Alcohol-based solutions Tuberculosis, MRSA, Listeria, Salmonella, Pseudonomas aeruginosa, Hepatitis B, Norovirus | NAV-CO2
Non-flammable Alcohol Vapor in Carbon Dioxide (NAV-CO2) systems were developed in Japan in the 1990s to sanitize hospitals and ambulances. These systems were developed to respond to a need for a safe, effective, and environmentally sound way to sanitizing without the use of toxic or corrosive chemicals.
# Theory of operation
NAV-CO2 systems use liquid CO2 as a propellant. NAV-CO2 systems combine Alcohol-based sanitizing solutions with a heated stream of CO2 liquid to create a vapor capable of penetrating small crevices and gaps. As CO2 and atomized Alcohol evaporate completely at room temperature, no residue remains. CO2 displaces oxygen, eliminating one of the elements needed to support combustion. Sanitizing chemicals such as quaternary ammonium can be added to alcohol based sanitizers to extend the killing time on surfaces. NAV-CO2 systems are used to sanitize contact surfaces where individuals may become infected. Hand washing and sanitizing surfaces with Alcohol-based solutions are effective methods for the prevention of nosocomial infection.
# Application
Hospitals, Ambulances, Nursing Homes, Public Waiting Areas and Food Processing Plants are likely places where disease causing bacteria and viruses are known to colonize. NAV-CO2 eliminates the use and disposal of toxic chemicals such as bleach and other commercial products.
# Effectiveness against Pathogens
Alcohol-based solutions Tuberculosis, MRSA, Listeria, Salmonella, Pseudonomas aeruginosa, Hepatitis B, Norovirus | https://www.wikidoc.org/index.php/NAV-CO2 | |
500e4ce5daacc795935406c06ea8bc1624aa64f2 | wikidoc | NDUFA10 | NDUFA10
NADH dehydrogenase 1 alpha subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFA10 gene. The NDUFA10 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Furthermore, reduced NDUFA10 expression levels due to FOXM1-directed hypermethylation are associated with human squamous cell carcinoma and may be related to other forms of cancer.
# Structure
The NDUFA10 gene is located on the q arm of chromosome 2 in position 37.3 and spans 68,031 base pairs. The gene produces a 41 kDa protein composed of 355 amino acids. NDUFA10 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA10 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.
# Function
The human NDUFA10 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
# Clinical significance
NDUFA10 demonstrated significantly downregulated mRNA expression levels in human squamous cell carcinoma, due to FOXM1-induced hypermethylation. FOXM1 is a known oncogene that has been implicated in all human cancer types. It operates by inhibiting tumor suppressor genes through promoter hypermethylation, among other mechanisms. Mutations in NDUFA10 have also been associated with Leigh disease resulting from complex I deficiency.
# Interactions
NDUFA10 has been shown to have 56 binary protein-protein interactions including 55 co-complex interactions. NDUFA10 appears to interact with RAB8A. | NDUFA10
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFA10 gene.[1][2] The NDUFA10 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[3][4] Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome.[1] Furthermore, reduced NDUFA10 expression levels due to FOXM1-directed hypermethylation are associated with human squamous cell carcinoma and may be related to other forms of cancer.[5]
# Structure
The NDUFA10 gene is located on the q arm of chromosome 2 in position 37.3 and spans 68,031 base pairs.[1] The gene produces a 41 kDa protein composed of 355 amino acids.[6][7] NDUFA10 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[3] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA10 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[8] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[1][4][9]
# Function
The human NDUFA10 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[1] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[3]
# Clinical significance
NDUFA10 demonstrated significantly downregulated mRNA expression levels in human squamous cell carcinoma, due to FOXM1-induced hypermethylation. FOXM1 is a known oncogene that has been implicated in all human cancer types. It operates by inhibiting tumor suppressor genes through promoter hypermethylation, among other mechanisms.[5] Mutations in NDUFA10 have also been associated with Leigh disease resulting from complex I deficiency.[10]
# Interactions
NDUFA10 has been shown to have 56 binary protein-protein interactions including 55 co-complex interactions. NDUFA10 appears to interact with RAB8A.[11] | https://www.wikidoc.org/index.php/NDUFA10 | |
e091c358528794cf866847dc30d65ae752c7c5e0 | wikidoc | NDUFA11 | NDUFA11
NADH dehydrogenase 1 alpha subcomplex subunit 11 is an enzyme that in humans is encoded by the NDUFA11 gene. The NDUFA11 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Mutations in this gene are associated with severe mitochondrial complex I deficiency.
# Structure
The NDUFA11 gene is located on the p arm of chromosome 19 in position 13.3 and spans 12,738 base pairs. The gene produces a 15 kDa protein composed of 141 amino acids. NDUFA11 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA11 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.
# Function
The human NDUFA11 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
# Clinical significance
Mutations in NDUFA11 and other Complex I subunit genes result in mitochondrial Complex I deficiency with autosomal recessive inheritance. Patients with these mutations display a wide range of clinical disorders and phenotypes, including lethal neonatal disease, adult-onset neurodegenerative disorders, macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh's syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease. There is no clear genotype-phenotype correlation, but most cases result from mutations in nuclear-encoded genes rather than mitochondrially-encoded genes. | NDUFA11
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 is an enzyme that in humans is encoded by the NDUFA11 gene.[1] The NDUFA11 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain[2][3] Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Mutations in this gene are associated with severe mitochondrial complex I deficiency.[4]
# Structure
The NDUFA11 gene is located on the p arm of chromosome 19 in position 13.3 and spans 12,738 base pairs.[4] The gene produces a 15 kDa protein composed of 141 amino acids.[5][6] NDUFA11 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[2] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA11 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[7] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[3][4][8]
# Function
The human NDUFA11 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2]
# Clinical significance
Mutations in NDUFA11 and other Complex I subunit genes result in mitochondrial Complex I deficiency with autosomal recessive inheritance. Patients with these mutations display a wide range of clinical disorders and phenotypes, including lethal neonatal disease, adult-onset neurodegenerative disorders, macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh's syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease. There is no clear genotype-phenotype correlation, but most cases result from mutations in nuclear-encoded genes rather than mitochondrially-encoded genes.[9] | https://www.wikidoc.org/index.php/NDUFA11 | |
3bca9fee38cd981f745a083db8ffeea2b23b0edf | wikidoc | NDUFA12 | NDUFA12
NADH dehydrogenase 1 alpha subcomplex subunit 12 is an enzyme that in humans is encoded by the NDUFA12 gene. The NDUFA12 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome that result from mitochondrial complex I deficiency.
# Structure
The NDUFA12 gene is located on the q arm of chromosome 12 in position 22 and spans 32,386 base pairs. The gene produces a 17 kDa protein composed of 145 amino acids. NDUFA12 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA12 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.
# Function
The human NDUFA12 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
# Clinical significance
Mutations to NDUFA12 are not frequently found to cause complex I deficiency on their own. NDUFA12 is an accessory subunit and the complex can still be found assembled and enzymatically active in its absence, though in reduced amounts and activity. However, a cytosine to tyrosine mutation at position 178 that leads to a premature stop codon has been found in place of arginine at amino acid 60, leading to delayed early development, loss of motor abilities, and basal ganglia lesions typical of Leigh's syndrome. | NDUFA12
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 is an enzyme that in humans is encoded by the NDUFA12 gene.[1][2][3] The NDUFA12 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[4][5] Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome that result from mitochondrial complex I deficiency.[3]
# Structure
The NDUFA12 gene is located on the q arm of chromosome 12 in position 22 and spans 32,386 base pairs.[3] The gene produces a 17 kDa protein composed of 145 amino acids.[6][7] NDUFA12 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[4] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA12 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[8] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[3][5][9]
# Function
The human NDUFA12 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[3] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[4]
# Clinical significance
Mutations to NDUFA12 are not frequently found to cause complex I deficiency on their own. NDUFA12 is an accessory subunit and the complex can still be found assembled and enzymatically active in its absence, though in reduced amounts and activity. However, a cytosine to tyrosine mutation at position 178 that leads to a premature stop codon has been found in place of arginine at amino acid 60, leading to delayed early development, loss of motor abilities, and basal ganglia lesions typical of Leigh's syndrome.[10] | https://www.wikidoc.org/index.php/NDUFA12 | |
0a72ec06c14ced9e0b0f96af75a2d1309646f462 | wikidoc | NDUFA13 | NDUFA13
NADH dehydrogenase 1 alpha subcomplex subunit 13 is an enzyme that in humans is encoded by the NDUFA13 gene. The NDUFA13 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.
# Structure
The NDUFA13 gene is located on the p arm of chromosome 19 in position 13.2 and spans 11,995 base pairs. The gene produces a 17 kDa protein composed of 144 amino acids. NDUFA13 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA13 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.
# Function
The human NDUFA13 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
NDUFA13 has a homologous protein known as GRIM-19, a cell-death regulatory protein. It is involved in interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This form of apoptotic activity is inhibited by interaction with viral IRF1. GRIM-19 prevents the transactivation of signal-transducer and activator of transcription 3 (STAT3) target genes but not other STAT family members.
# Clinical significance
The homologous protein to NDUFA13, GRIM-19, may play a role in Chron's disease (CD), an inflammatory bowel disease (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for NF-κB activation, a key component in regulating the immune response to infection.
# Interactions
NDUFA13 has been shown to interact with STAT3. | NDUFA13
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 is an enzyme that in humans is encoded by the NDUFA13 gene.[1][2][3][4] The NDUFA13 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[5][6]
# Structure
The NDUFA13 gene is located on the p arm of chromosome 19 in position 13.2 and spans 11,995 base pairs.[4] The gene produces a 17 kDa protein composed of 144 amino acids.[7][8] NDUFA13 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[5] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA13 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[9] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[4][6][10]
# Function
The human NDUFA13 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[5]
NDUFA13 has a homologous protein known as GRIM-19, a cell-death regulatory protein. It is involved in interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This form of apoptotic activity is inhibited by interaction with viral IRF1. GRIM-19 prevents the transactivation of signal-transducer and activator of transcription 3 (STAT3) target genes but not other STAT family members.[9]
# Clinical significance
The homologous protein to NDUFA13, GRIM-19, may play a role in Chron's disease (CD), an inflammatory bowel disease (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for NF-κB activation, a key component in regulating the immune response to infection.[9][11]
# Interactions
NDUFA13 has been shown to interact with STAT3.[12] | https://www.wikidoc.org/index.php/NDUFA13 | |
2ff01925f151f5703653ed60dc51632dd82139de | wikidoc | NDUFAB1 | NDUFAB1
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa is a protein that in humans is encoded by the NDUFAB1 gene. The NDUFAB1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.
# Structure
The NDUFAB1 gene is located on the p arm of chromosome 16 at position 12.2 and it spans 15,327 base pairs. The NDUFAB1 gene produces a 17.4 kDa protein composed of 156 amino acids. NDUFAB1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. NDUFAB1 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.
# Function
The human NDUFAB1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. However, NDUFAB1 is an accessory subunit of the complex that is believed not to be involved in catalysis. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
# Clinical Significance
In a genome-wide association study (GWAS) meta-analysis conducted across European and African American populations, the NDUFAB1 gene and two other genes (MFAP3L and PALB2) were identified as genetic loci significantly associated with anxiety disorders (ADs). Since the comorbidity of ADs arises from their shared genetic basis, these candidate genetic loci may become therapeutic targets for AD treatments. Moreover, a study to identify small molecule drug targets for Tetralogy of Fallot (TOF), a congenital malformation of the heart, found the NDUFAB1 gene to be a major hub gene of differentially expressed genes in TOF. | NDUFAB1
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa is a protein that in humans is encoded by the NDUFAB1 gene.[1] The NDUFAB1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2]
# Structure
The NDUFAB1 gene is located on the p arm of chromosome 16 at position 12.2 and it spans 15,327 base pairs.[1] The NDUFAB1 gene produces a 17.4 kDa protein composed of 156 amino acids.[3][4] NDUFAB1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[2] NDUFAB1 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[1]
# Function
The human NDUFAB1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[1] However, NDUFAB1 is an accessory subunit of the complex that is believed not to be involved in catalysis.[5] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2]
# Clinical Significance
In a genome-wide association study (GWAS) meta-analysis conducted across European and African American populations, the NDUFAB1 gene and two other genes (MFAP3L and PALB2) were identified as genetic loci significantly associated with anxiety disorders (ADs). Since the comorbidity of ADs arises from their shared genetic basis, these candidate genetic loci may become therapeutic targets for AD treatments.[6] Moreover, a study to identify small molecule drug targets for Tetralogy of Fallot (TOF), a congenital malformation of the heart, found the NDUFAB1 gene to be a major hub gene of differentially expressed genes in TOF.[7] | https://www.wikidoc.org/index.php/NDUFAB1 | |
6eb18eb0a1d8d18388ca1694533d8364b30e3c0c | wikidoc | NDUFAF1 | NDUFAF1
Complex I intermediate-associated protein 30, mitochondrial (CIA30), or NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1), is a protein that in humans is encoded by the NDUFAF1 or CIA30 gene. The NDUFAF1 gene encodes a human homolog of a Neurospora crassa protein involved in the assembly of complex I. The NDUFAF1 protein is an assembly factor of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Variants of the NDUFAF1 gene are associated with hypertrophic cardiomyopathy, leukodystrophy, and cardioencephalomyopathy.
# Structure
NDUFAF1 is located on the q arm of chromosome 15 in position 15.1. The NDUFAF1 gene produces a 37.8 kDa protein composed of 327 amino acids. NDUFAF1 is associated to complexes of 600 and 700 kDa. Complex I is structured in a bipartite L-shaped configuration, which is made up of a peripheral matrix arm, consisting of flavoproteins and iron-sulfur proteins involved in electron transfer, and a membrane arm, consisting of mtDNA-encoded subunits involved in ubiquinone reduction and proton pumping. NDUFAF1 has been shown to interact with assembly intermediates and may play roles in the correct assembly and combination of the peripheral arm to the complete membrane arm as well as in the stabilization and scaffolding of those intermediates through those close interactions.
# Function
NDUFAF1 is an assembly factor that is important for the correct assembly of NADH dehydrogenase (ubiquinone). It ensures the correct combination of complex intermediates and is necessary for the correct functioning of NADH dehydrogenase (ubiquinone). Specifically, NDUFAF1 binds to the large membrane arm intermediate and is involved in the combination of the small and large membrane arm intermediates of complex I. It has also been suggested that NDUFAF1 is involved in the stabilization and scaffolding of assembly intermediates and that this role may be more prominent than its part in intermediate combination.
# Clinical Significance
Mutations in NDUFAF1 can result in mitochondrial deficiencies and associated disorders. A disorder of the mitochondrial respiratory chain can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
In a patient with missense mutations in NDUFAF1, fatal infantile hypertrophic cardiomyopathy was diagnosed. In this case, complex I disassembly resulted in a mitochondrial cardiomyopathy with marked lactic acidosis. Another patient, a child with a compound heterozygous mutation (c.278A > G; c.247G > A) within exon 2 in the NDUFAF1 gene, was diagnosed with leukodystrophy associated with mitochondrial complex I deficiency. Signs and symptoms included regression of mental and motor development, white matter lesions, peripheral neuropathy with high muscle tension and hyperreflexia of limbs, and high levels of lactate and creatine kinase. The parents were found to be heterozygous carriers for the mutation. A third patient was found to have a mutation in both alleles of the NDUFAF1 gene and was diagnosed with cardioencephalomyopathy and reduced levels and activity of complex I.
# Interactions
In addition to co-complexes, NDUFAF1 has protein-protein interactions with PNLIPRP1, TMEM97, TMEM86B, YIPF6, SLC30A2, ATIC, and MAGEA11. | NDUFAF1
Complex I intermediate-associated protein 30, mitochondrial (CIA30), or NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1 (NDUFAF1), is a protein that in humans is encoded by the NDUFAF1 or CIA30 gene.[1][2][3][4][5] The NDUFAF1 gene encodes a human homolog of a Neurospora crassa protein involved in the assembly of complex I.[3] The NDUFAF1 protein is an assembly factor of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[6] Variants of the NDUFAF1 gene are associated with hypertrophic cardiomyopathy, leukodystrophy, and cardioencephalomyopathy.[7][8][9]
# Structure
NDUFAF1 is located on the q arm of chromosome 15 in position 15.1.[3] The NDUFAF1 gene produces a 37.8 kDa protein composed of 327 amino acids.[10][11] NDUFAF1 is associated to complexes of 600 and 700 kDa.[4] Complex I is structured in a bipartite L-shaped configuration, which is made up of a peripheral matrix arm, consisting of flavoproteins and iron-sulfur proteins involved in electron transfer, and a membrane arm, consisting of mtDNA-encoded subunits involved in ubiquinone reduction and proton pumping.[9] NDUFAF1 has been shown to interact with assembly intermediates and may play roles in the correct assembly and combination of the peripheral arm to the complete membrane arm as well as in the stabilization and scaffolding of those intermediates through those close interactions.[4]
# Function
NDUFAF1 is an assembly factor that is important for the correct assembly of NADH dehydrogenase (ubiquinone). It ensures the correct combination of complex intermediates and is necessary for the correct functioning of NADH dehydrogenase (ubiquinone). Specifically, NDUFAF1 binds to the large membrane arm intermediate and is involved in the combination of the small and large membrane arm intermediates of complex I. It has also been suggested that NDUFAF1 is involved in the stabilization and scaffolding of assembly intermediates and that this role may be more prominent than its part in intermediate combination.[4]
# Clinical Significance
Mutations in NDUFAF1 can result in mitochondrial deficiencies and associated disorders. A disorder of the mitochondrial respiratory chain can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[12]
In a patient with missense mutations in NDUFAF1, fatal infantile hypertrophic cardiomyopathy was diagnosed. In this case, complex I disassembly resulted in a mitochondrial cardiomyopathy with marked lactic acidosis.[7] Another patient, a child with a compound heterozygous mutation (c.278A > G; c.247G > A) within exon 2 in the NDUFAF1 gene, was diagnosed with leukodystrophy associated with mitochondrial complex I deficiency. Signs and symptoms included regression of mental and motor development, white matter lesions, peripheral neuropathy with high muscle tension and hyperreflexia of limbs, and high levels of lactate and creatine kinase. The parents were found to be heterozygous carriers for the mutation.[8] A third patient was found to have a mutation in both alleles of the NDUFAF1 gene and was diagnosed with cardioencephalomyopathy and reduced levels and activity of complex I.[9]
# Interactions
In addition to co-complexes, NDUFAF1 has protein-protein interactions with PNLIPRP1,[13] TMEM97,[14] TMEM86B,[15] YIPF6,[16] SLC30A2,[17] ATIC,[18] and MAGEA11.[19] | https://www.wikidoc.org/index.php/NDUFAF1 | |
9fe2f1ac1d21fd8d4d39d7dbfb0fe27592eb6f27 | wikidoc | NDUFAF2 | NDUFAF2
NADH:ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2), also known as B17.2L or NDUFA12L is a protein that in humans is encoded by the NDUFAF2, or B17.2L, gene. The NDUFAF2 protein is a chaperone involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.
# Structure
NDUFAF2 is located on the q arm of chromosome 5 in position 12.1. The NDUFAF2 gene produces a 20 kDa protein composed of 169 amino acids. The protein is a chaperone of the complex I NDUFA12 subunit family.
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The NDUFAF2 gene encodes a complex I assembly factor, B17.2L, that is important for the correct function of the mitochondrial respiratory chain. Specifically, B17.2L acts as a molecular chaperone, associating with an 830 kDa subassembly in the late stages of complex I assembly.
# Clinical significance
Mutations in NDUFAF2 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Clinically, NDUFAF2 mutations have been associated with progressive encephalopathy and Leigh disease.
# Interactions
In addition to co-complexes, NDUFAF2 has protein-protein interactions with CYB5B SEC22B, TMEM97, TMEM201, SPG21, LPAR3, STX8,OPTN. | NDUFAF2
NADH:ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2), also known as B17.2L or NDUFA12L is a protein that in humans is encoded by the NDUFAF2, or B17.2L, gene.[1] The NDUFAF2 protein is a chaperone involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2][3] Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.[1]
# Structure
NDUFAF2 is located on the q arm of chromosome 5 in position 12.1.[1] The NDUFAF2 gene produces a 20 kDa protein composed of 169 amino acids.[4][5] The protein is a chaperone of the complex I NDUFA12 subunit family.[6][7]
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The NDUFAF2 gene encodes a complex I assembly factor, B17.2L, that is important for the correct function of the mitochondrial respiratory chain.[1] Specifically, B17.2L acts as a molecular chaperone, associating with an 830 kDa subassembly in the late stages of complex I assembly.[3]
# Clinical significance
Mutations in NDUFAF2 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[6][7] Clinically, NDUFAF2 mutations have been associated with progressive encephalopathy[3] and Leigh disease.[8][9]
# Interactions
In addition to co-complexes, NDUFAF2 has protein-protein interactions with CYB5B SEC22B, TMEM97, TMEM201, SPG21, LPAR3, STX8,OPTN.[10] | https://www.wikidoc.org/index.php/NDUFAF2 | |
6051fb17b7694e67feaaff6ed6ea9219706a4eff | wikidoc | NDUFAF3 | NDUFAF3
NADH dehydrogenase 1 alpha subcomplex assembly factor 3, also known as 2P1, E3-3, or C3orf60, is a protein that in humans is encoded by the NDUFAF3 gene. NDUFAF3 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated severe complex I deficiency and Leigh syndrome.
# Structure
NDUFAF3 is located on the p arm of chromosome 3 in position 21.31 and has 7 exons. The NDUFAF3 gene produces a 20.4 kDa protein composed of 184 amino acids. NDUFAF3 encodes two isoforms which have a common DUF498 domain. Predictions indicate that isoform A contains an additional 35 amino acid N-terminal sequence and is thus longer than isoform B. The extra sequence may be involved in mitochondrial targeting, supporting NDUFAF3's function in mitochondrial assembly.
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the mitochondrial inner membrane. The NDUFAF3 gene encodes a mitochondrial complex I assembly protein that localizes to the mitochondrial inner membrane and interacts with complex I subunits and is important for the correct function of the mitochondrial respiratory chain.
NDUFAF3 colocalizes, comigrates to several assembly intermediates, and is codependent with NDUFAF4 from the early to late stages of complex I assembly. In addition to their close interactions with each other, NDUFAF3 and NDUFAF4 interact with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in a translation-dependent early assembly mechanism. It is also suggested that NDUFAF3 is involved in coupling mitochondrial translation with membrane insertion in the process of complex I assembly.
# Clinical Significance
Mutations in NDUFAF3 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Mutations have included the homozygous variants c.494C > T; p.(Ala165Val), c.365 G→C resulting in R122P, and c.2 T→C resulting in M1T. Clinically, NDUFAF3 mutations have been associated with Leigh syndrome and severe complex I deficiency. Some common signs and symptoms include lactic acidosis, nystagmus, hypotonia, and cerebral lesions.
# Interactions
In addition to co-complexes, NDUFAF3 has protein-protein interactions with NDUFAF4 and SNRPA. | NDUFAF3
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3, also known as 2P1, E3-3, or C3orf60, is a protein that in humans is encoded by the NDUFAF3 gene.[1][2][3] NDUFAF3 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[4][5] Mutations in this gene have been associated severe complex I deficiency and Leigh syndrome.[1][5][6]
# Structure
NDUFAF3 is located on the p arm of chromosome 3 in position 21.31 and has 7 exons.[1] The NDUFAF3 gene produces a 20.4 kDa protein composed of 184 amino acids.[7][8] NDUFAF3 encodes two isoforms which have a common DUF498 domain. Predictions indicate that isoform A contains an additional 35 amino acid N-terminal sequence and is thus longer than isoform B. The extra sequence may be involved in mitochondrial targeting, supporting NDUFAF3's function in mitochondrial assembly.[5]
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the mitochondrial inner membrane.[9] The NDUFAF3 gene encodes a mitochondrial complex I assembly protein that localizes to the mitochondrial inner membrane and interacts with complex I subunits and is important for the correct function of the mitochondrial respiratory chain.[1][5]
NDUFAF3 colocalizes, comigrates to several assembly intermediates, and is codependent with NDUFAF4 from the early to late stages of complex I assembly. In addition to their close interactions with each other, NDUFAF3 and NDUFAF4 interact with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in a translation-dependent early assembly mechanism. It is also suggested that NDUFAF3 is involved in coupling mitochondrial translation with membrane insertion in the process of complex I assembly.[5]
# Clinical Significance
Mutations in NDUFAF3 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[2][3] Mutations have included the homozygous variants c.494C > T; p.(Ala165Val),[6] c.365 G→C resulting in R122P, and c.2 T→C resulting in M1T.[5] Clinically, NDUFAF3 mutations have been associated with Leigh syndrome[6] and severe complex I deficiency.[5] Some common signs and symptoms include lactic acidosis, nystagmus, hypotonia, and cerebral lesions.[5][6]
# Interactions
In addition to co-complexes, NDUFAF3 has protein-protein interactions with NDUFAF4[10] and SNRPA.[11] | https://www.wikidoc.org/index.php/NDUFAF3 | |
c765ccbe203a38617ff4fb7e00c7ef2dd0d13d07 | wikidoc | NDUFAF4 | NDUFAF4
NADH:ubiquinone oxidoreductase complex assembly factor 4, (NDUFAF4) also known as Hormone-regulated proliferation-associated protein of 20 kDa, (HRPAP20) or C6orf66 is a protein that in humans is encoded by the NDUFAF4 gene. NDUFAF4 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with complex I deficiency and infantile mitochondrial encephalomyopathy. Elevations in HRPAP20 have also been implicated in breast cancer.
# Structure
NDUFAF4 is located on the q arm of chromosome 6 in position 16.1 and has 3 exons. The NDUFAF4 gene produces a 23.7 kDa protein composed of 203 amino acids. HRPAP20 is a phosphoprotein, containing a phosphate group attachment and, potentially, multiple kinase recognition sequences. Additionally, it has a CaM-binding sequence that allows it to interact with calmodulin (CaM), which itself is involved in numerous cellular processes.
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. NDUFAF4 encodes a complex I assembly factor that is important for the correct assembly and function of complex I. NDUFAF4 colocalizes, comigrates to several assembly intermediates, and is codependent with NDUFAF3 from the early to late stages of complex I assembly. In addition to their close interactions with each other, NDUFAF4 and NDUFAF3 interact with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in a translation-dependent early assembly mechanism. NDUFAF4 has also been shown to play a role in growth and apoptosis regulation through a CaM-mediated mechanism involving MMP-9 secretion.
# Clinical Significance
Mutations in NDUFAF4 (HRPAP20) have been associated with mitochondrial complex I deficiency, infantile mitochondrial encephalomyopathy. Additionally, research analyzing HRPAP20's effect on human cancer cells have suggested that it plays a role in tumor metastasis, malignant progression, and breast cancer.
Mitochondrial diseases are disorders that are the result of the dysfunction of the mitochondrial respiratory chain. They can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Pathogenic mutations have been linked to changes in a 2.6 Mb critical region (97.17–99.77 Mb) on chromosome 6 and have included a T→C substitution at p. 194 in exon 2 that predicts a Leu65Pro variant. Clinically, NDUFAF4 mutations have been associated with infantile mitochondrial encephalomyopathy, with lactic acidosis, nystagmus, hypotonia, cardiomyopathy, cerebral atrophy, and generalized tonic-clonic convulsions as some possible symptoms.
HRPAP20 was found to be significantly elevated in patient breast tumors as compared to normal tissue. Further analysis using tumor cell lines with constitutively expressed HRPAP20 suggests that it increases the invasiveness, proliferation, and apoptotic suppression of breast cancer cells. This is often indicative of tumor metastasis and malignant progression.
# Interactions
NDUFAF4 (HRPAP20) has been shown to interact closely with NDUFAF3 as well as with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in the mitochondrial inner membrane. HRPAP20 also interacts with calmodulin (CaM) in a mechanism that results in increased MMP-9 secretion, associated with increased invasiveness in breast cancer cells. In addition to co-complexes, NDUFAF4 has protein-protein interactions with WDR26. | NDUFAF4
NADH:ubiquinone oxidoreductase complex assembly factor 4, (NDUFAF4) also known as Hormone-regulated proliferation-associated protein of 20 kDa, (HRPAP20) or C6orf66 is a protein that in humans is encoded by the NDUFAF4 gene.[1][2] NDUFAF4 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[3][4] Mutations in this gene have been associated with complex I deficiency and infantile mitochondrial encephalomyopathy.[1][2][4] Elevations in HRPAP20 have also been implicated in breast cancer.[5]
# Structure
NDUFAF4 is located on the q arm of chromosome 6 in position 16.1 and has 3 exons.[1] The NDUFAF4 gene produces a 23.7 kDa protein composed of 203 amino acids.[6][7] HRPAP20 is a phosphoprotein, containing a phosphate group attachment and, potentially, multiple kinase recognition sequences. Additionally, it has a CaM-binding sequence that allows it to interact with calmodulin (CaM), which itself is involved in numerous cellular processes.[5]
# Function
NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. NDUFAF4 encodes a complex I assembly factor that is important for the correct assembly and function of complex I.[1] NDUFAF4 colocalizes, comigrates to several assembly intermediates, and is codependent with NDUFAF3 from the early to late stages of complex I assembly. In addition to their close interactions with each other, NDUFAF4 and NDUFAF3 interact with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in a translation-dependent early assembly mechanism.[8] NDUFAF4 has also been shown to play a role in growth and apoptosis regulation through a CaM-mediated mechanism involving MMP-9 secretion.[5]
# Clinical Significance
Mutations in NDUFAF4 (HRPAP20) have been associated with mitochondrial complex I deficiency,[1] infantile mitochondrial encephalomyopathy.[4] Additionally, research analyzing HRPAP20's effect on human cancer cells have suggested that it plays a role in tumor metastasis, malignant progression, and breast cancer.[5]
Mitochondrial diseases are disorders that are the result of the dysfunction of the mitochondrial respiratory chain. They can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[2][9] Pathogenic mutations have been linked to changes in a 2.6 Mb critical region (97.17–99.77 Mb) on chromosome 6 and have included a T→C substitution at p. 194 in exon 2 that predicts a Leu65Pro variant. Clinically, NDUFAF4 mutations have been associated with infantile mitochondrial encephalomyopathy, with lactic acidosis, nystagmus, hypotonia, cardiomyopathy, cerebral atrophy, and generalized tonic-clonic convulsions as some possible symptoms.[4]
HRPAP20 was found to be significantly elevated in patient breast tumors as compared to normal tissue. Further analysis using tumor cell lines with constitutively expressed HRPAP20 suggests that it increases the invasiveness, proliferation, and apoptotic suppression of breast cancer cells. This is often indicative of tumor metastasis and malignant progression.[5]
# Interactions
NDUFAF4 (HRPAP20) has been shown to interact closely with NDUFAF3 as well as with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in the mitochondrial inner membrane.[8] HRPAP20 also interacts with calmodulin (CaM) in a mechanism that results in increased MMP-9 secretion, associated with increased invasiveness in breast cancer cells.[5] In addition to co-complexes, NDUFAF4 has protein-protein interactions with WDR26.[10] | https://www.wikidoc.org/index.php/NDUFAF4 | |
69e532a0d869b569ba93c9240c25686cefae1028 | wikidoc | NDUFAF5 | NDUFAF5
NADH:ubiquinone oxidoreductase complex assembly factor 5, also known as Arginine-hydroxylase NDUFAF5, or Putative methyltransferase NDUFAF5, is a protein that in humans is encoded by the NDUFAF5 gene. The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene.
# Structure
NDUFAF5 is located on the p arm of Chromosome 20 in position 12.1 and spans 36,554 base pairs. The NDUFAF5 gene produces a 30 kDa protein composed of 267 amino acids. The presumed structure of the c-terminal of the protein has been found to resemble that of the known secondary structure of RdmB. NDUFAF5 contains the S-adenosylmethionine dependent methyltransferase domain, which contains the GxGxG signature sequence, and the S-adenosylmethionine-binding motif which are common in most SAM-dependent methyltransferases. This arginine-hydroxylase is involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages. Complex I is composed of 45 evolutionally conserved core subunits, including both mitochondrial DNA and nuclear encoded subunits. One of its arms is embedded in the inner membrane of the mitochondria, and the other is embedded in the organelle. The two arms are arranged in an L-shaped manner. The total molecular weight of the complex is 1MDa.
# Function
The NDUFAF5 gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. Their role is integral to co-factor insertions and in utilizing sub-assemblies for building complex I. It does so by catalyzing the hydroxylation of Arg-73 in the NDUFS7 subunit of human complex I, which occurs before the peripheral and membrane arm juncture formation in the beginning stages of complex I assembly. The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. Though the exact biochemical function of NDUFAF5 is not yet known, mutations in this gene results in mitochondrial complex I deficiency. NDUFAF5 is also known to be a member of the 7β-strand family of SAM-dependent methyltransferases.
# Clinical significance
Mutations in NDUFAF5 is known to result in mitochondrial diseases and associated disorders. It is majorly associated with a complex I deficiency, a deficiency in the first complex of the mitochondrial respiratory chain. Suppression of the NDUFAF5 gene has been found to lead to the loss of both peripheral and membrane arms of complex I associated with NDUFS7 and ND1. This then leads to the progressive loss of complex I, causing the deficiency. Such disorders involving the dysfunction of the mitochondrial respiratory chain may cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Mutations in NDUFAF5 has also been common patients with Leigh syndrome, an early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions.
# Interactions
In addition to co-subunits for complex I, NDUFAF5 has protein-protein interactions with NDUFAF8 (for stabilization), and NDUFS7. | NDUFAF5
NADH:ubiquinone oxidoreductase complex assembly factor 5, also known as Arginine-hydroxylase NDUFAF5, or Putative methyltransferase NDUFAF5, is a protein that in humans is encoded by the NDUFAF5 gene.[1] The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene.[1]
# Structure
NDUFAF5 is located on the p arm of Chromosome 20 in position 12.1 and spans 36,554 base pairs.[1] The NDUFAF5 gene produces a 30 kDa protein composed of 267 amino acids.[2][3] The presumed structure of the c-terminal of the protein has been found to resemble that of the known secondary structure of RdmB. NDUFAF5 contains the S-adenosylmethionine dependent methyltransferase domain, which contains the GxGxG signature sequence, and the S-adenosylmethionine-binding motif which are common in most SAM-dependent methyltransferases.[4][5] This arginine-hydroxylase is involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages.[6] Complex I is composed of 45 evolutionally conserved core subunits, including both mitochondrial DNA and nuclear encoded subunits. One of its arms is embedded in the inner membrane of the mitochondria, and the other is embedded in the organelle. The two arms are arranged in an L-shaped manner. The total molecular weight of the complex is 1MDa.[4]
# Function
The NDUFAF5 gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly.[4] Their role is integral to co-factor insertions and in utilizing sub-assemblies for building complex I. It does so by catalyzing the hydroxylation of Arg-73 in the NDUFS7 subunit of human complex I, which occurs before the peripheral and membrane arm juncture formation in the beginning stages of complex I assembly.[4] The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. Though the exact biochemical function of NDUFAF5 is not yet known, mutations in this gene results in mitochondrial complex I deficiency. NDUFAF5 is also known to be a member of the 7β-strand family of SAM-dependent methyltransferases.[1][6]
# Clinical significance
Mutations in NDUFAF5 is known to result in mitochondrial diseases and associated disorders. It is majorly associated with a complex I deficiency, a deficiency in the first complex of the mitochondrial respiratory chain.[7] Suppression of the NDUFAF5 gene has been found to lead to the loss of both peripheral and membrane arms of complex I associated with NDUFS7 and ND1. This then leads to the progressive loss of complex I, causing the deficiency.[4] Such disorders involving the dysfunction of the mitochondrial respiratory chain may cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Mutations in NDUFAF5 has also been common patients with Leigh syndrome, an early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions.[4][6]
# Interactions
In addition to co-subunits for complex I, NDUFAF5 has protein-protein interactions with NDUFAF8 (for stabilization), and NDUFS7.[6] | https://www.wikidoc.org/index.php/NDUFAF5 | |
26a7019a116bfd5bc28eb6c7e324ddebc9a69be8 | wikidoc | NDUFAF7 | NDUFAF7
Protein arginine methyltransferase NDUFAF7, mitochondrial, also known as NADH:ubiquinone oxidoreductase complex assembly factor 7 (NDUFAF7), MidA, C2orf56, or PRO1853, is a protein that in humans is encoded by the NDUFAF7 gene. NDUFAF7 is a methyltransferase mitochondrial assembly enzyme involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in NDUFAF7 have been associated with pathologic myopia and complex I deficiency.
# Structure
NDUFAF7 is located on the p arm of chromosome 2 in position 22.2 and has 14 exons. The NDUFAF7 gene produces a 49.2 kDa protein composed of 441 amino acids. NDUFAF7 is believed to be a part of the S-adenosylmethionine-dependent methyltransferase family. This family has a characteristic seven-β-strand protein fold. NDUFAF7 is a type II arginine methyltransferase, meaning that its enzymatic activity produces a symmetrical ω-NG,NG′-dimethylarginine. It has a methyltransferase domain and an N-terminal sequence that corresponds to the recognized mitochondrial-targeting peptide. NDUFAF7's stoichometry is disputed with some findings indicating that it is a homodimer, while others denote it to be monomeric.
# Function
The NDUFAF7 gene encodes an assembly factor protein that is localized in the mitochondria and which helps in the assembly and stabilization of complex I, a large multi-subunit enzyme in the mitochondrial respiratory chain. NADH:ubiquinone oxidoreductase (complex I) is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein of NDUFAF7 is a methyltransferase that symmetrically dimethylates the ω-NG,NG′ atoms of Arg85 of subunit NDUFS2 of complex I in the early stages of its assembly. This interaction between NDUFAF7 and NDUFS2 is believed to be transient and it is suggested that this methylation stabilizes a 400 kDa subcomplex primarily associated with the peripheral arm of complex I. Without this methylation, the amount of intact complex I is significantly reduced, illustrating NDUFAF7's importance to the mitochondrial respiratory chain. A pseudogene related to this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants.
# Clinical significance
Defects in NDUFAF7 may be a cause of susceptibility to pathologic myopia, a genetically heterogeneous disorder characterized by extreme, familial, early-onset vision loss and described as myopia accompanied by severe deformation of the eye besides excessive elongation of the eye. This defect, a heterozygous D266E missense mutation, also resulted in reduced complex I activity. Due to is role in early assembly of complex I, it has been suggested that mutations affecting NDUFAF7 may be lethal.
# Interactions
NDUFAF7 interacts transiently with NDUFS2, dimethylating Arg85 on the subunit. A correlation between the presence of MidA and NDUFS7 was also identified. In addition to co-complexes, NDUFAF4 has protein-protein interactions with LRRK2, q5nfq6_fratt, and q5ngw2_fratt. | NDUFAF7
Protein arginine methyltransferase NDUFAF7, mitochondrial, also known as NADH:ubiquinone oxidoreductase complex assembly factor 7 (NDUFAF7), MidA, C2orf56, or PRO1853, is a protein that in humans is encoded by the NDUFAF7 gene. NDUFAF7 is a methyltransferase mitochondrial assembly enzyme involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[1][2][3] Mutations in NDUFAF7 have been associated with pathologic myopia and complex I deficiency.[2][4]
# Structure
NDUFAF7 is located on the p arm of chromosome 2 in position 22.2 and has 14 exons.[1] The NDUFAF7 gene produces a 49.2 kDa protein composed of 441 amino acids.[5][6] NDUFAF7 is believed to be a part of the S-adenosylmethionine-dependent methyltransferase family. This family has a characteristic seven-β-strand protein fold. NDUFAF7 is a type II arginine methyltransferase, meaning that its enzymatic activity produces a symmetrical ω-NG,NG′-dimethylarginine.[7] It has a methyltransferase domain and an N-terminal sequence that corresponds to the recognized mitochondrial-targeting peptide.[8] NDUFAF7's stoichometry is disputed with some findings indicating that it is a homodimer,[8] while others denote it to be monomeric.[9][2]
# Function
The NDUFAF7 gene encodes an assembly factor protein that is localized in the mitochondria and which helps in the assembly and stabilization of complex I, a large multi-subunit enzyme in the mitochondrial respiratory chain.[1][8] NADH:ubiquinone oxidoreductase (complex I) is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane.[10] The encoded protein of NDUFAF7 is a methyltransferase that symmetrically dimethylates the ω-NG,NG′ atoms of Arg85 of subunit NDUFS2 of complex I in the early stages of its assembly. This interaction between NDUFAF7 and NDUFS2 is believed to be transient and it is suggested that this methylation stabilizes a 400 kDa subcomplex primarily associated with the peripheral arm of complex I. Without this methylation, the amount of intact complex I is significantly reduced, illustrating NDUFAF7's importance to the mitochondrial respiratory chain. A pseudogene related to this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants.[1][7]
# Clinical significance
Defects in NDUFAF7 may be a cause of susceptibility to pathologic myopia, a genetically heterogeneous disorder characterized by extreme, familial, early-onset vision loss and described as myopia accompanied by severe deformation of the eye besides excessive elongation of the eye. This defect, a heterozygous D266E missense mutation, also resulted in reduced complex I activity.[2][4] Due to is role in early assembly of complex I, it has been suggested that mutations affecting NDUFAF7 may be lethal.[7]
# Interactions
NDUFAF7 interacts transiently with NDUFS2, dimethylating Arg85 on the subunit.[7] A correlation between the presence of MidA and NDUFS7 was also identified.[8] In addition to co-complexes, NDUFAF4 has protein-protein interactions with LRRK2, q5nfq6_fratt, and q5ngw2_fratt.[11] | https://www.wikidoc.org/index.php/NDUFAF7 | |
8854bb54f302adac0bfec0809e2ac10e02c96920 | wikidoc | NDUFB10 | NDUFB10
NADH dehydrogenase 1 beta subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFB10 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 10 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.
# Gene
The NDUFB10 gene is located on the p arm of chromosome 16 in position 13.3 and is 2,459 base pairs long.
# Structure
The NDUFB10 protein weighs 21 kDa and is composed of 172 amino acids. NDUFB10 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.
# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix. | NDUFB10
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 is an enzyme that in humans is encoded by the NDUFB10 gene.[1][2][3] NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 10 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.[4]
# Gene
The NDUFB10 gene is located on the p arm of chromosome 16 in position 13.3 and is 2,459 base pairs long.[5][6]
# Structure
The NDUFB10 protein weighs 21 kDa and is composed of 172 amino acids.[5][6] NDUFB10 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[4] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[3]
# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.[3] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[4] | https://www.wikidoc.org/index.php/NDUFB10 | |
ae5a69966cc0c1248ea22c46ae9c6bd5776ead11 | wikidoc | NDUFB11 | NDUFB11
NADH dehydrogenase 1 beta subcomplex subunit 11, mitochondrial (NADH-ubiquinone oxidoreductase ESSS subunit) is an enzyme that in humans is encoded by the NDUFB11 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain. NDUFB11 mutations have been associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency.
# Gene
The NDUFB11 gene is located on the p arm of chromosome X in position 11.23 and is 2,994 base pairs long.
# Protein
The NDUFB11 protein weighs 17 kDa and is composed of 153 amino acids. NDUFB11 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes.
# Structure
The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.
# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.
# Clinical significance
Mutations in the human gene are associated with linear skin defects with mitochondrial complex I deficiency and microphthalmia with linear skin defects syndrome. Mitochondrial complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. In cases of pathogenic NDUFB11 mutations, complex I deficiency with lactic acidosis and sideroblastic anemia has been found to occur. Mutations in NDUFB11 have also been linked to microphthalmia with linear skin defects syndrome with neurological and cardiac abnormalities.
# Interactions
NDUFB11 has been shown to have 55 binary protein-protein interactions including 32 co-complex interactions. NDUFB11 appears to interact with FATE1, GPR42, CLDN7, GJB1, HIBADH, EBP, GPR152, GPR101, TIMMDC1, TIMMDC1, PPBP, and CRELD2. | NDUFB11
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial (NADH-ubiquinone oxidoreductase ESSS subunit) is an enzyme that in humans is encoded by the NDUFB11 gene.[1][2][3] NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.[4] NDUFB11 mutations have been associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency.[3]
# Gene
The NDUFB11 gene is located on the p arm of chromosome X in position 11.23 and is 2,994 base pairs long.[5][6]
# Protein
The NDUFB11 protein weighs 17 kDa and is composed of 153 amino acids.[5][6] NDUFB11 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes.
# Structure
The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[4] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[3]
# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.[3] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[4]
# Clinical significance
Mutations in the human gene are associated with linear skin defects with mitochondrial complex I deficiency and microphthalmia with linear skin defects syndrome.[3] Mitochondrial complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders.[7][8] In cases of pathogenic NDUFB11 mutations, complex I deficiency with lactic acidosis and sideroblastic anemia has been found to occur.[9] Mutations in NDUFB11 have also been linked to microphthalmia with linear skin defects syndrome with neurological and cardiac abnormalities.[10]
# Interactions
NDUFB11 has been shown to have 55 binary protein-protein interactions including 32 co-complex interactions. NDUFB11 appears to interact with FATE1, GPR42, CLDN7, GJB1, HIBADH, EBP, GPR152, GPR101, TIMMDC1, TIMMDC1, PPBP, and CRELD2.[11] | https://www.wikidoc.org/index.php/NDUFB11 | |
3841d9f7a3610c31ff2a5108ebb06b4ee1220846 | wikidoc | NEUROD1 | NEUROD1
Neurogenic differentiation 1 (NeuroD1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.
It is a member of the NeuroD family of basic helix-loop-helix (bHLH) transcription factors. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus.
NeuroD1 is found to convert reactive glial cells into functional neurons in the mouse brain in vivo
# Interactions
NEUROD1 has been shown to interact with MAP3K10, MAFA and Cyclin D1. | NEUROD1
Neurogenic differentiation 1 (NeuroD1), also called β2,[1] is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.
It is a member of the NeuroD family of basic helix-loop-helix (bHLH) transcription factors. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus.[2]
NeuroD1 is found to convert reactive glial cells into functional neurons in the mouse brain in vivo[3]
# Interactions
NEUROD1 has been shown to interact with MAP3K10,[4] MAFA[5] and Cyclin D1.[6] | https://www.wikidoc.org/index.php/NEUROD1 | |
a41243ba65609236f4a0148bedab2fe04afd84a3 | wikidoc | NFKBIL1 | NFKBIL1
NF-kappa-B inhibitor-like protein 1 is a protein that in humans is encoded by the NFKBIL1 gene.
# Function
This gene encodes a divergent member of the I-kappa-B family of proteins. Its function is unclear. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6.
# Model organisms
Model organisms have been used in the study of NFKBIL1 function. A conditional knockout mouse line called Nfkbil1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | NFKBIL1
NF-kappa-B inhibitor-like protein 1 is a protein that in humans is encoded by the NFKBIL1 gene.[1][2]
# Function
This gene encodes a divergent member of the I-kappa-B family of proteins. Its function is unclear. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6.[2]
# Model organisms
Model organisms have been used in the study of NFKBIL1 function. A conditional knockout mouse line called Nfkbil1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9] | https://www.wikidoc.org/index.php/NFKBIL1 | |
4a61a8a4e3a49ac3f2d88fd290ab7dfac20afc47 | wikidoc | NKIRAS2 | NKIRAS2
NF-κB inhibitor interacting Ras-like 2 is a protein that in humans is encoded by the NKIRAS2 gene.
# Model organisms
Model organisms have been used in the study of NKIRAS2 function. A conditional knockout mouse line, called Nkiras2tm1a(EUCOMM)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 one tests were carried out, but no significant abnormalities were observed. | NKIRAS2
NF-κB inhibitor interacting Ras-like 2 is a protein that in humans is encoded by the NKIRAS2 gene.[1]
# Model organisms
Model organisms have been used in the study of NKIRAS2 function. A conditional knockout mouse line, called Nkiras2tm1a(EUCOMM)Wtsi[4][5] 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.[6][7][8]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[3][9] Twenty one tests were carried out, but no significant abnormalities were observed.[3] | https://www.wikidoc.org/index.php/NKIRAS2 | |
ce22f91adc6cb55cfe64e10d3cf9a3f7c634eb1b | wikidoc | Notch 3 | Notch 3
Neurogenic locus notch homolog protein 3 is a protein that in humans is encoded by the NOTCH3 gene.
# Function
This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined.
# Pathology
Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mutations in NOTCH3 have also been identified in a Turkish family with Alzheimer's disease. Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.
Mutations in NOTCH3 are associated to lateral meningocele syndrome .
# Pharmaceutical target
Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers. Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors. | Notch 3
Neurogenic locus notch homolog protein 3 is a protein that in humans is encoded by the NOTCH3 gene.[1][2]
# Function
This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined.
# Pathology
Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).[2] Mutations in NOTCH3 have also been identified in a Turkish family with Alzheimer's disease.[3] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.[4]
Mutations in NOTCH3 are associated to lateral meningocele syndrome .[5]
# Pharmaceutical target
Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers.[6] Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.[7] | https://www.wikidoc.org/index.php/NOTCH3 | |
39c3d52d0ef984aefa1e1c32fa3532a3b1db3f92 | wikidoc | Nebulin | Nebulin
Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. It is a very large protein (600–900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during sarcomere assembly. Other functions of nebulin, such as a role in cell signaling, remain uncertain.
Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a calcium-calmodulin sensitive manner.
Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.
A smaller member of the nebulin protein family, termed nebulette, is expressed in cardiac muscle.
# Structure
The structure of the SH3 domain of nebulin was determined by NMR. The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).
# Knockout phenotype
As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as animal models of nemaline myopathy. | Nebulin
Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. It is a very large protein (600–900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during sarcomere assembly.[1] Other functions of nebulin, such as a role in cell signaling, remain uncertain.
Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a calcium-calmodulin sensitive manner.[2]
Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.[3]
A smaller member of the nebulin protein family, termed nebulette, is expressed in cardiac muscle.
# Structure
The structure of the SH3 domain of nebulin was determined by NMR.[4] The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).
# Knockout phenotype
As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues[5] demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues[6] had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as animal models of nemaline myopathy. | https://www.wikidoc.org/index.php/Nebulin | |
794620889ecb867af1a3a4be34da640bc8c0f55f | wikidoc | Nefopam | Nefopam
# Overview
Nefopam (brand names: Acupan, Silentan, Nefadol and Ajan) is a centrally-acting but non-opioid analgesic drug of the benzoxazocine chemical class which was developed by Riker Laboratories in the 1960s. It is widely used, mainly in European countries, for the relief of moderate to severe pain as an alternative to opioid analgesic drugs. Animal studies have shown that nefopam has a potentiating (analgesic-sparing) effect on morphine and other opioids by broadening the antinociceptive action of the opioid and possibly other mechanisms, generally lowering the dose requirements of both when they are used concomitantly.
# Use
Nefopam has additional action in the prevention of shivering, which may be a side effect of other drugs used in surgery. Nefopam was significantly more effective than aspirin as an analgesic in one clinical trial, although with a greater incidence of side effects such as sweating, dizziness and nausea, especially at higher doses. Nefopam is around a third to half the potency and slightly less effective as an analgesic compared to morphine, or oxycodone, but tends to produce fewer side effects, does not produce respiratory depression, and has much less abuse potential, and so is useful either as an alternative to opioids, or as an adjunctive treatment for use alongside opioid(s) or other analgesics. Nefopam is also used to combat severe hiccups.
# Side effects
Common side effects include nausea, nervousness, dry mouth, light-headedness and urinary retention. Less common side effects include vomiting, blurred vision, drowsiness, sweating, insomnia, headache, confusion, hallucinations, tachycardia, aggravation of angina and rarely a temporary and benign pink discolouration of the skin or erythema multiforme.
## Contraindications
It is contraindicated in people with convulsive disorders, those that have received treatment with irreversible monoamine oxidase inhibitors such as phenelzine, tranylcypromine or isocarboxazid within the past 30 days and those with myocardial infarction pain, mostly due to a lack of safety data in these conditions.
## Interactions
It has additive anticholinergic and sympathomimetic effects with other agents with these properties. Its use should be avoided in people receiving some types of antidepressants (tricyclic antidepressants or monoamine oxidase inhibitors) as there is the potential for serotonin syndrome or hypertensive crises to result.
## Recreational use and overdose
Recreational use of nefopam and death from overdose have both been reported, although these events are less common with nefopam than with opioid analgesic drugs. Overdose usually manifests with convulsions, hallucinations, tachycardia and hyperdynamic circulation. Treatment is usually supportive, managing cardiovascular complications with beta-blockers and limiting absorption with activated charcoal.
# Pharmacology
The mechanism of action of nefopam is not well understood, although inhibition of serotonin, dopamine and noradrenaline reuptake is thought to be involved in its analgesic effects, and there may be other modes of action such as through histamine H3 receptors and glutamate. Recently, like its analogue orphenadrine which also has analgesic effects, nefopam has been found to act as a voltage-gated sodium channel blocker, and this may in part or fully mediate its antinociceptive effects. | Nefopam
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Nefopam (brand names: Acupan, Silentan, Nefadol and Ajan) is a centrally-acting but non-opioid analgesic drug of the benzoxazocine chemical class which was developed by Riker Laboratories in the 1960s.[1] It is widely used, mainly in European countries, for the relief of moderate to severe pain as an alternative to opioid analgesic drugs. Animal studies have shown that nefopam has a potentiating (analgesic-sparing) effect on morphine and other opioids by broadening the antinociceptive action of the opioid and possibly other mechanisms, generally lowering the dose requirements of both when they are used concomitantly.[2]
# Use
Nefopam has additional action in the prevention of shivering, which may be a side effect of other drugs used in surgery.[3] Nefopam was significantly more effective than aspirin as an analgesic in one clinical trial,[4] although with a greater incidence of side effects such as sweating, dizziness and nausea, especially at higher doses.[5][6] Nefopam is around a third to half the potency and slightly less effective as an analgesic compared to morphine,[7][8][9] or oxycodone,[10] but tends to produce fewer side effects, does not produce respiratory depression,[11] and has much less abuse potential, and so is useful either as an alternative to opioids, or as an adjunctive treatment for use alongside opioid(s) or other analgesics.[9][12] Nefopam is also used to combat severe hiccups.[13]
# Side effects
Common side effects include nausea, nervousness, dry mouth, light-headedness and urinary retention.[14] Less common side effects include vomiting, blurred vision, drowsiness, sweating, insomnia, headache, confusion, hallucinations, tachycardia, aggravation of angina and rarely a temporary and benign pink discolouration of the skin or erythema multiforme.[14]
## Contraindications
It is contraindicated in people with convulsive disorders, those that have received treatment with irreversible monoamine oxidase inhibitors such as phenelzine, tranylcypromine or isocarboxazid within the past 30 days and those with myocardial infarction pain, mostly due to a lack of safety data in these conditions.[14]
## Interactions
It has additive anticholinergic and sympathomimetic effects with other agents with these properties.[14] Its use should be avoided in people receiving some types of antidepressants (tricyclic antidepressants or monoamine oxidase inhibitors) as there is the potential for serotonin syndrome or hypertensive crises to result.[14]
## Recreational use and overdose
Recreational use of nefopam and death from overdose have both been reported,[15] although these events are less common with nefopam than with opioid analgesic drugs.[16] Overdose usually manifests with convulsions, hallucinations, tachycardia and hyperdynamic circulation.[14] Treatment is usually supportive, managing cardiovascular complications with beta-blockers and limiting absorption with activated charcoal.[14]
# Pharmacology
The mechanism of action of nefopam is not well understood, although inhibition of serotonin, dopamine and noradrenaline reuptake is thought to be involved in its analgesic effects,[17][18][19] and there may be other modes of action such as through histamine H3 receptors[20] and glutamate.[21] Recently, like its analogue orphenadrine which also has analgesic effects, nefopam has been found to act as a voltage-gated sodium channel blocker, and this may in part or fully mediate its antinociceptive effects.[22] | https://www.wikidoc.org/index.php/Nefopam | |
fbf212037e42b9beb724761527497e50aff9eea2 | wikidoc | Neoteny | Neoteny
Neoteny (Template:IPA) is the retention, by adults in a species, of traits previously seen only in juveniles (pedomorphosis/paedomorphosis), and is a subject studied in the field of developmental biology. In neoteny, the physiological (or somatic) development of an animal or organism is slowed or delayed. Ultimately this process results in the retention, in the adults of a species, of juvenile physical characteristics well into maturity. The English word neoteny is borrowed from the German Neotenie, the latter constructed from the Greek νέος (young) and τείνειν (to extend). The standard adjectival form is "neotenous", although "neotenic" is often used.
In vertebrate biology, neoteny is most easily identified when sexually mature, completely viable juveniles or larvae are found.
Specific individual traits that differ in descendant organisms, when compared to ancestors, are sometimes called neotenies; humans, for example, appear to have several neotenies in comparison to chimpanzees.
# Neoteny in evolution
Neoteny plays a role in evolution, as a means by which, over generations, a species can undergo a significant physical change. In such cases, a species’ neotenous form becomes its “normal” mature form, no longer dependent upon environmental triggers to inhibit maturity. The mechanism for this could be a mutation in, or interactions between: genes involved in maturation, changing their function to impede this process.
Neoteny is not the only contributing factor affecting maturation in species that may have undergone neotenous changes over the course of their evolution, and its actual involvement in the following examples is not well understood:
- flightless birds—physical proportions resemble those of the chicks of flighted birds;
- humans—with traits such as sparse body hair and enlarged heads reminiscent of baby primates. Lactose tolerance in adults is a form of neoteny now considered normal in some European populations and their descendants while most other humans are lactose intolerant as adults. It corresponds to a mutation that permits the digestion of lactose beyond the lactation period.
- pets, such as dogs—which share many physical features with the immature wolf (these same traits were found during the development of the tame silver fox). Such puppy-like traits may have made early dogs seem "cute" and less threatening than wolves, leading to both natural and artificial selection of such dogs.
It is possible that the origin of the chordates (the phylum including all vertebrates) was the result of an instance of neoteny. Molecular evidence suggests that the nearest relatives of the chordates are the tunicates, marine filter feeders. Although sessile in their adult, sexually mature form, tunicates have a motile larval dispersal form, which has a notochord similar to that found in chordates. At some point, the motile larvae of the tunicate became sexually mature before metamorphosis. As a sexually active pelagic organism it had considerable feeding and habitat colonization advantages over the sessile form, so was at an evolutionary advantage. However, the alternative - that the sessile form developed later and the pelagic form was ancestral - is also thought possible.
# Neoteny in humans
Neoteny in humans can be seen in different aspects. It can be compared with other great ape species, between the sexes and between individuals.
## Other species
There is controversy over whether adult humans exhibit certain neotenous features, or juvenile characteristics, that are not evidenced in other great ape species. Stephen Jay Gould was an advocate of the view that humans are a neotenous species of chimpanzee; the argument being that juvenile chimpanzees have an almost-identical bone structure to humans, and that the chimpanzee’s ability to learn seems to be cut off upon reaching maturity.
## Sexes
While neoteny is not necessarily a physical state experienced by humans, paedomorphic characteristics in women are widely acknowledged as desirable by men . For instance, vellus hair is a juvenile characteristic. However, while men develop longer, coarser, thicker, and darker terminal hair through sexual differentiation, women do not, leaving their vellus hair visible.
Desmond Morris discusses the importance of neoteny in human biology in The Naked Ape, The Human Animal, and The Human Zoo.
## Individuals
Paedomorphic variations not only exist between the sexes, but also between individuals, with some people displaying more characteristics of neoteny than others. This trend carries over to variations among ethnic groups as well.
Bruce Charlton, Reader in evolutionary psychiatry at Newcastle University U.K., suggests that there may be such a thing as "psychological neoteny." Due to recent changes in culture, he says, “In a psychological sense, some contemporary individuals never actually become adults.” Delayed maturity may be a consequence of later parenthood, itself caused by more prolonged formal education - especially among women
# Animal kingdom
One example of a neotenic trait in vertebrates is the salamander species axolotl, which usually remains fully aquatic as it matures. Other salamanders, such as the widespread tiger salamander of North America, may retain the external gills usually only present in immature individuals, as adults in some populations in marginal habitats.
# Neoteny and progenesis
Neoteny and progenesis are both mechanisms that result in paedomorphosis. Neoteny delays physiological, but not sexual, maturity. Comparatively, progenesis speeds up sexual, but not physiological, maturity. Progenetic organisms achieve sexual maturity in their juvenile state. This is most commonly found among certain amphibians and insects. | Neoteny
Neoteny (Template:IPA) is the retention, by adults in a species, of traits previously seen only in juveniles (pedomorphosis/paedomorphosis), and is a subject studied in the field of developmental biology. In neoteny, the physiological (or somatic) development of an animal or organism is slowed or delayed. Ultimately this process results in the retention, in the adults of a species, of juvenile physical characteristics well into maturity. The English word neoteny is borrowed from the German Neotenie, the latter constructed from the Greek νέος (young) and τείνειν (to extend). The standard adjectival form is "neotenous", although "neotenic" is often used.
In vertebrate biology, neoteny is most easily identified when sexually mature, completely viable juveniles or larvae are found.
Specific individual traits that differ in descendant organisms, when compared to ancestors, are sometimes called neotenies; humans, for example, appear to have several neotenies in comparison to chimpanzees.
# Neoteny in evolution
Neoteny plays a role in evolution, as a means by which, over generations, a species can undergo a significant physical change. In such cases, a species’ neotenous form becomes its “normal” mature form, no longer dependent upon environmental triggers to inhibit maturity. The mechanism for this could be a mutation in, or interactions between: genes involved in maturation, changing their function to impede this process.
Neoteny is not the only contributing factor affecting maturation in species that may have undergone neotenous changes over the course of their evolution, and its actual involvement in the following examples is not well understood:
- flightless birds—physical proportions resemble those of the chicks of flighted birds;
- humans—with traits such as sparse body hair and enlarged heads reminiscent of baby primates. Lactose tolerance in adults is a form of neoteny now considered normal in some European populations and their descendants while most other humans are lactose intolerant as adults. It corresponds to a mutation that permits the digestion of lactose beyond the lactation period.
- pets, such as dogs—which share many physical features with the immature wolf (these same traits were found during the development of the tame silver fox). Such puppy-like traits may have made early dogs seem "cute" and less threatening than wolves, leading to both natural and artificial selection of such dogs.
It is possible that the origin of the chordates (the phylum including all vertebrates) was the result of an instance of neoteny. Molecular evidence suggests that the nearest relatives of the chordates are the tunicates, marine filter feeders. Although sessile in their adult, sexually mature form, tunicates have a motile larval dispersal form, which has a notochord similar to that found in chordates. At some point, the motile larvae of the tunicate became sexually mature before metamorphosis. As a sexually active pelagic organism it had considerable feeding and habitat colonization advantages over the sessile form, so was at an evolutionary advantage. However, the alternative - that the sessile form developed later and the pelagic form was ancestral - is also thought possible.[citation needed]
# Neoteny in humans
Neoteny in humans can be seen in different aspects. It can be compared with other great ape species, between the sexes and between individuals.
## Other species
There is controversy over whether adult humans exhibit certain neotenous features, or juvenile characteristics, that are not evidenced in other great ape species. Stephen Jay Gould was an advocate of the view that humans are a neotenous species of chimpanzee; the argument being that juvenile chimpanzees have an almost-identical bone structure to humans, and that the chimpanzee’s ability to learn seems to be cut off upon reaching maturity.
## Sexes
While neoteny is not necessarily a physical state experienced by humans, paedomorphic characteristics in women are widely acknowledged as desirable by men [1]. For instance, vellus hair is a juvenile characteristic. However, while men develop longer, coarser, thicker, and darker terminal hair through sexual differentiation, women do not, leaving their vellus hair visible.
Desmond Morris discusses the importance of neoteny in human biology in The Naked Ape, The Human Animal, and The Human Zoo.
## Individuals
Paedomorphic variations not only exist between the sexes, but also between individuals, with some people displaying more characteristics of neoteny than others. This trend carries over to variations among ethnic groups as well.
Bruce Charlton, Reader in evolutionary psychiatry at Newcastle University U.K., suggests that there may be such a thing as "psychological neoteny." [1] Due to recent changes in culture, he says, “In a psychological sense, some contemporary individuals never actually become adults.” Delayed maturity may be a consequence of later parenthood, itself caused by more prolonged formal education - especially among women [2]
# Animal kingdom
One example of a neotenic trait in vertebrates is the salamander species axolotl, which usually remains fully aquatic as it matures. Other salamanders, such as the widespread tiger salamander of North America, may retain the external gills usually only present in immature individuals, as adults in some populations in marginal habitats.
# Neoteny and progenesis
Neoteny and progenesis are both mechanisms that result in paedomorphosis. Neoteny delays physiological, but not sexual, maturity. Comparatively, progenesis speeds up sexual, but not physiological, maturity. Progenetic organisms achieve sexual maturity in their juvenile state. This is most commonly found among certain amphibians and insects. | https://www.wikidoc.org/index.php/Neoteny | |
6ddcaf4f03ea2db28dcdd1e75ea136c01a9ad868 | wikidoc | Nephron | Nephron
Steven C. Campbell, M.D., Ph.D.
# Overview
A nephron (from Greek νεφρός (nephros) meaning "kidney") is the basic structural and functional unit of the kidney. Its chief function is to regulate water and soluble substances like Sodium salts by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.
# Types of nephrons
Two general classes of nephrons are cortical nephrons and juxtamedullary nephrons, both of which are classified according to the location of their associated renal corpuscle. Cortical nephrons have their renal corpuscle in the superficial renal cortex, while the renal corpuscles of juxtamedullary nephrons are located near the renal medulla. The nomenclature for cortical nephrons varies, with some sources distinguishing between superficial cortical nephrons and midcortical nephrons; other sources simply call all non-juxtamedullary nephrons superficial nephrons.
Functionally, cortical and juxtamedullary nephrons have distinct roles. Cortical nephrons (85% of all nephrons) mainly perform excretory and regulatory functions, while juxtamedullary nephrons (15% of nephrons) concentrate and dilute urine.
# Anatomy
Each nephron is composed of an initial filtering component (the "renal corpuscle") and a tubule specialized for reabsorption and secretion (the "renal tubule"). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification.
## Renal corpuscle
Composed of a glomerulus and Bowman's capsule, the renal corpuscle (or "Malphigian corpuscle") is the beginning of the nephron. It is the nephron's initial filtering component.
## Renal tubule
The flow of the renal tubule is as follows:
After traveling the length of the distal convoluted tubule, only about 1% of water remains, and the remaining salt content is negligible.
## Collecting duct system
Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the collecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's countercurrent multiplier system.
Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). As much as three-fourths of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or diluted. An increase in ADH is an indication of dehydration, while water sufficiency results in low ADH allowing for diluted urine.
Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron).
Urine leaves the medullary collecting ducts through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter.
Because it has a different origin during the development of the urinary and reproductive organs than the rest of the nephron, the collecting duct is sometimes not considered a part of the nephron. Instead of originating from the metanephrogenic blastema, the collecting duct originates from the ureteric bud.
## Juxtaglomerular apparatus
The juxtaglomerular apparatus occurs near the site of contact between the thick ascending limb and the afferent arteriole. It contains three components:
Juxtaglomerular cells are the site of renin synthesis and secretion and thus play a critical role in the renin-angiotensin system.
# Clinical relevance
Because of its importance in body fluid regulation, the nephron is a common target of drugs that treat high blood pressure and edema. These drugs, called diuretics, inhibit the ability of the nephron to retain water, thereby increasing the amount of urine produced. | Nephron
Template:Infobox Anatomy
Template:Search infobox
Steven C. Campbell, M.D., Ph.D.
# Overview
A nephron (from Greek νεφρός (nephros) meaning "kidney") is the basic structural and functional unit of the kidney. Its chief function is to regulate water and soluble substances like Sodium salts by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.
# Types of nephrons
Two general classes of nephrons are cortical nephrons and juxtamedullary nephrons, both of which are classified according to the location of their associated renal corpuscle. Cortical nephrons have their renal corpuscle in the superficial renal cortex, while the renal corpuscles of juxtamedullary nephrons are located near the renal medulla. The nomenclature for cortical nephrons varies, with some sources distinguishing between superficial cortical nephrons and midcortical nephrons;[1] other sources simply call all non-juxtamedullary nephrons superficial nephrons.[2]
Functionally, cortical and juxtamedullary nephrons have distinct roles. Cortical nephrons (85% of all nephrons) mainly perform excretory and regulatory functions, while juxtamedullary nephrons (15% of nephrons) concentrate and dilute urine.[2]
# Anatomy
Each nephron is composed of an initial filtering component (the "renal corpuscle") and a tubule specialized for reabsorption and secretion (the "renal tubule"). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification.
## Renal corpuscle
Composed of a glomerulus and Bowman's capsule, the renal corpuscle (or "Malphigian corpuscle") is the beginning of the nephron. It is the nephron's initial filtering component.
## Renal tubule
The flow of the renal tubule is as follows:
After traveling the length of the distal convoluted tubule, only about 1% of water remains, and the remaining salt content is negligible.
## Collecting duct system
Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the collecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's countercurrent multiplier system.
Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). As much as three-fourths of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or diluted. An increase in ADH is an indication of dehydration, while water sufficiency results in low ADH allowing for diluted urine.
Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron).
Urine leaves the medullary collecting ducts through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter.
Because it has a different origin during the development of the urinary and reproductive organs than the rest of the nephron, the collecting duct is sometimes not considered a part of the nephron. Instead of originating from the metanephrogenic blastema, the collecting duct originates from the ureteric bud.
## Juxtaglomerular apparatus
The juxtaglomerular apparatus occurs near the site of contact between the thick ascending limb and the afferent arteriole. It contains three components:
Juxtaglomerular cells are the site of renin synthesis and secretion and thus play a critical role in the renin-angiotensin system.
# Clinical relevance
Because of its importance in body fluid regulation, the nephron is a common target of drugs that treat high blood pressure and edema. These drugs, called diuretics, inhibit the ability of the nephron to retain water, thereby increasing the amount of urine produced. | https://www.wikidoc.org/index.php/Nephron | |
d44257465c565782d8d12520aa9258d45fdae49f | wikidoc | Neutron | Neutron
# Overview
In physics, the neutron is a subatomic particle with no net electric charge and a mass of 939.573 MeV/c² or 1.008 664 915 (78) u (1.6749 × 10−27 kg, slightly more than a proton). Its spin is ½. Its antiparticle is called the antineutron. The neutron, along with the proton, is a nucleon.
The nuclei of all atoms consist of protons and neutrons, except the lightest isotope of hydrogen which has only a single proton. The number of protons defines the type of element the atom forms. The number of neutrons determines the isotope of an element, therefore isotopes are atoms of the same element (i.e. atomic number) but differing atomic masses due to a different number of neutrons. For example, the carbon-12 isotope has 6 protons and 6 neutrons, while the carbon-14 isotope has 6 protons and 8 neutrons.
A neutron consists of two down quarks and one up quark. Since it has three quarks, it is classified as a baryon.
# Neutron stability and beta decay
Outside the nucleus, free neutrons are unstable and have a mean lifetime of 885.7±0.8 seconds (about 15 minutes), decaying by emission of a negative electron and antineutrino to become a proton:
\hbox{n}\to\hbox{p}+\hbox{e}^-+\overline{\nu}_{\mathrm{e}}. This decay mode, known as beta decay, can also transform the character of neutrons within unstable nuclei.
Inside of a bound nucleus, protons can also transform via beta decay into neutrons. In this case, the transformation may occur by emission of a positron (antielectron) and neutrino (instead of an antineutrino): \hbox{p}\to\hbox{n}+\hbox{e}^{+}+{\nu}_{\mathrm{e}}. The transformation of a proton to a neutron inside of a nucleus is also possible through electron capture: \hbox{p}+\hbox{e}^{-}\to\hbox{n}+{\nu}_{\mathrm{e}} . Positron capture by neutrons in nuclei that contain an excess of neutrons is also possible, but is hindered due to the fact positrons are repelled by the nucleus, and furthermore, quickly annihilate when they encounter negative electrons.
When bound inside of a nucleus, the instability of a single neutron to beta decay is balanced against the instability that would be acquired by the nucleus as a whole if an additional proton were to participate in repulsive interactions with the other protons that are already present in the nucleus. As such, although free neutrons are unstable, bound neutrons are not necessarily so. The same reasoning explains why protons, which are stable in empty space, may transform into neutrons when bound inside of a nucleus.
Beta decay and electron capture are types of radioactive decay and are both governed by the weak interaction.
# Interactions
The neutron interacts through all four fundamental interactions: the electromagnetic, weak nuclear, strong nuclear and gravitational interactions.
Although the neutron has zero net charge, it may interact electromagnetically in two ways: first, the neutron has a magnetic moment of the same order as the proton (see neutron magnetic moment); second, it is composed of electrically charged quarks. Thus, the electromagnetic interaction is primarily important to the neutron in deep inelastic scattering and in magnetic interactions.
The neutron experiences the weak interaction through beta decay into a proton, electron and electron antineutrino. It experiences the gravitational force as does any energetic body; however, gravity is so weak that it may be neglected in particle physics experiments.
The most important force to neutrons is the strong interaction. This interaction is responsible for the binding of the neutron's three quarks into a single particle. The residual strong force is responsible for the binding of neutrons and protons together into nuclei. This nuclear force plays the leading role when neutrons pass through matter. Unlike charged particles or photons, the neutron cannot lose energy by ionizing atoms. Rather, the neutron goes on its way unchecked until it makes a head-on collision with an atomic nucleus. For this reason, neutron radiation is extremely penetrating.
# Detection
The common means of detecting a charged particle by looking for a track of ionization (such as in a cloud chamber) does not work for neutrons directly. Neutrons that elastically scatter off atoms can create an ionization track that is detectable, but the experiments are not as simple to carry out; other means for detecting neutrons, consisting of allowing them to interact with atomic nuclei, are more commonly used.
A common method for detecting neutrons involves converting the energy released from such reactions into electrical signals. The nuclides 3He, 6Li, 10B, 233U, 235U, 237Np and 239Pu are useful for this purpose. A good discussion on neutron detection is found in chapter 14 of the book Radiation Detection and Measurement by Glenn F. Knoll (John Wiley & Sons, 1979).
# Uses
The neutron plays an important role in many nuclear reactions. For example, neutron capture often results in neutron activation, inducing radioactivity. In particular, knowledge of neutrons and their behavior has been important in the development of nuclear reactors and nuclear weapons.
Cold, thermal and hot neutron radiation is commonly employed in neutron scattering facilities, where the radiation is used in a similar way one uses X-rays for the analysis of condensed matter. Neutrons are complementary to the latter in terms of atomic contrasts by different scattering cross sections; sensitivity to magnetism; energy range for inelastic neutron spectroscopy; and deep penetration into matter.
The development of "neutron lenses" based on total internal reflection within hollow glass capillary tubes or by reflection from dimpled aluminum plates has driven ongoing research into neutron microscopy and neutron/gamma ray tomography.
One use of neutron emitters is the detection of light nuclei, particularly the hydrogen found in water molecules. When a fast neutron collides with a light nucleus, it loses a large fraction of its energy. By measuring the rate at which slow neutrons return to the probe after reflecting off of hydrogen nuclei, a neutron probe may determine the water content in soil.
# Sources
Due to the fact that free neutrons are unstable, they can be obtained only from nuclear disintegrations, nuclear reactions, and high-energy reactions (such as in cosmic radiation showers or accelerator collisions). Free neutron beams are obtained from neutron sources by neutron transport. For access to intense neutron sources, researchers must go to specialist facilities, such as the ISIS facility in the UK, which is currently the world's most intense pulsed neutron and muon source.
Neutrons' lack of total electric charge prevents engineers or experimentalists from being able to steer or accelerate them. Charged particles can be accelerated, decelerated, or deflected by electric or magnetic fields. However, these methods have no effect on neutrons except for a small effect of a magnetic field because of the neutron's magnetic moment.
# Discovery
In 1930 Walther Bothe and H. Becker in Germany found that if the very energetic alpha particles emitted from polonium fell on certain light elements, specifically beryllium, boron, or lithium, an unusually penetrating radiation was produced. At first this radiation was thought to be gamma radiation, although it was more penetrating than any gamma rays known, and the details of experimental results were very difficult to interpret on this basis. The next important contribution was reported in 1932 by Irène Joliot-Curie and Frédéric Joliot in Paris. They showed that if this unknown radiation fell on paraffin or any other hydrogen-containing compound it ejected protons of very high energy. This was not in itself inconsistent with the assumed gamma ray nature of the new radiation, but detailed quantitative analysis of the data became increasingly difficult to reconcile with such a hypothesis. Finally, in 1932 the physicist James Chadwick in England performed a series of experiments showing that the gamma ray hypothesis was untenable. He suggested that in fact the new radiation consisted of uncharged particles of approximately the mass of the proton, and he performed a series of experiments verifying his suggestion. Such uncharged particles were eventually called neutrons, apparently from the Latin root for neutral and the Greek ending -on (by imitation of electron and proton).
# Anti-neutron
The antineutron is the antiparticle of the neutron. It was discovered by Bruce Cork in the year 1956, a year after the antiproton was discovered.
CPT-symmetry puts strong constraints on the relative properties of particles and antiparticles and, therefore, is open to stringent tests. The fractional difference in the masses of the neutron and antineutron is (9±5)×10−5. Since the difference is only about 2 standard deviations away from zero, this does not give any convincing evidence of CPT-violation.
# Current developments
## Electric dipole moment
An experiment at the Institut Laue-Langevin has attempted to measure an electric dipole, or separation of charges, within the neutron, and is consistent with an electric dipole moment of zero. These results are important in developing theories that go beyond the Standard Model, but are inconsistent with it due to the lack of explanation of the fundamental interactions.
## Tetraneutrons
The existence of stable clusters of four neutrons, or tetraneutrons, has been hypothesised by a team led by Francisco-Miguel Marqués at the CNRS Laboratory for Nuclear Physics based on observations of the disintegration of beryllium-14 nuclei. This is particularly interesting, because current theory suggests that these clusters should not be stable.
# Protection
Exposure to neutrons can be hazardous, since the interaction of neutrons with molecules in the body can cause disruption to molecules and atoms, and can also cause reactions which give rise to other forms of radiation (such as protons). The normal precautions of radiation protection apply: avoid exposure, stay as far from the source as possible, and keep exposure time to a minimum. Some particular thought must be given to how to protect from neutron exposure, however. For other types of radiation, e.g. alpha particles, beta particles, or gamma rays, material of a high atomic number and with high density make for good shielding; frequently lead is used. However, this approach will not work with neutrons, since the absorption of neutrons does not increase straightforwardly with atomic number, as it does with alpha, beta, and gamma radiation. Instead one needs to look at the particular interactions neutrons have with matter (see the section on detection above). For example, hydrogen rich materials are often used to shield against neutrons, since ordinary hydrogen both scatters and slows neutrons. This often means that simple concrete blocks or even paraffin-loaded plastic blocks afford better protection from neutrons than do far more dense materials. After slowing, neutrons may then be absorbed with an isotope which has high affinity for slow neutrons without causing secondary capture-radiation, such as lithium-6.
Hydrogen-rich ordinary water effects neutron absorption in nuclear fission reactors: usually neutrons are so strongly absorbed by normal water that fuel-enrichement with fissionable isotope, is required. The deuterium in heavy water has a very much lower absorption affinity for neutrons than does protium (normal light hydrogen). Deuterium is therefore used in CANDU-type reactors, in order to slow ("moderate") neutron velocity, so that they are more effective at causing nuclear fission, without capturing them. | Neutron
Template:Infobox Particle
# Overview
In physics, the neutron is a subatomic particle with no net electric charge and a mass of 939.573 MeV/c² or 1.008 664 915 (78) u (1.6749 × 10−27 kg, slightly more than a proton). Its spin is ½. Its antiparticle is called the antineutron. The neutron, along with the proton, is a nucleon.
The nuclei of all atoms consist of protons and neutrons, except the lightest isotope of hydrogen which has only a single proton. The number of protons defines the type of element the atom forms. The number of neutrons determines the isotope of an element, therefore isotopes are atoms of the same element (i.e. atomic number) but differing atomic masses due to a different number of neutrons. For example, the carbon-12 isotope has 6 protons and 6 neutrons, while the carbon-14 isotope has 6 protons and 8 neutrons.
A neutron consists of two down quarks and one up quark. Since it has three quarks, it is classified as a baryon.
# Neutron stability and beta decay
Outside the nucleus, free neutrons are unstable and have a mean lifetime of 885.7±0.8 seconds (about 15 minutes), decaying by emission of a negative electron and antineutrino to become a proton:[1]
<math>\hbox{n}\to\hbox{p}+\hbox{e}^-+\overline{\nu}_{\mathrm{e}}</math>. This decay mode, known as beta decay, can also transform the character of neutrons within unstable nuclei.
Inside of a bound nucleus, protons can also transform via beta decay into neutrons. In this case, the transformation may occur by emission of a positron (antielectron) and neutrino (instead of an antineutrino): <math>\hbox{p}\to\hbox{n}+\hbox{e}^{+}+{\nu}_{\mathrm{e}}</math>. The transformation of a proton to a neutron inside of a nucleus is also possible through electron capture: <math>\hbox{p}+\hbox{e}^{-}\to\hbox{n}+{\nu}_{\mathrm{e}}</math> . Positron capture by neutrons in nuclei that contain an excess of neutrons is also possible, but is hindered due to the fact positrons are repelled by the nucleus, and furthermore, quickly annihilate when they encounter negative electrons.
When bound inside of a nucleus, the instability of a single neutron to beta decay is balanced against the instability that would be acquired by the nucleus as a whole if an additional proton were to participate in repulsive interactions with the other protons that are already present in the nucleus. As such, although free neutrons are unstable, bound neutrons are not necessarily so. The same reasoning explains why protons, which are stable in empty space, may transform into neutrons when bound inside of a nucleus.
Beta decay and electron capture are types of radioactive decay and are both governed by the weak interaction.
# Interactions
The neutron interacts through all four fundamental interactions: the electromagnetic, weak nuclear, strong nuclear and gravitational interactions.
Although the neutron has zero net charge, it may interact electromagnetically in two ways: first, the neutron has a magnetic moment of the same order as the proton (see neutron magnetic moment);[2] second, it is composed of electrically charged quarks. Thus, the electromagnetic interaction is primarily important to the neutron in deep inelastic scattering and in magnetic interactions.
The neutron experiences the weak interaction through beta decay into a proton, electron and electron antineutrino. It experiences the gravitational force as does any energetic body; however, gravity is so weak that it may be neglected in particle physics experiments.
The most important force to neutrons is the strong interaction. This interaction is responsible for the binding of the neutron's three quarks into a single particle. The residual strong force is responsible for the binding of neutrons and protons together into nuclei. This nuclear force plays the leading role when neutrons pass through matter. Unlike charged particles or photons, the neutron cannot lose energy by ionizing atoms. Rather, the neutron goes on its way unchecked until it makes a head-on collision with an atomic nucleus. For this reason, neutron radiation is extremely penetrating.
# Detection
The common means of detecting a charged particle by looking for a track of ionization (such as in a cloud chamber) does not work for neutrons directly. Neutrons that elastically scatter off atoms can create an ionization track that is detectable, but the experiments are not as simple to carry out; other means for detecting neutrons, consisting of allowing them to interact with atomic nuclei, are more commonly used.
A common method for detecting neutrons involves converting the energy released from such reactions into electrical signals. The nuclides 3He, 6Li, 10B, 233U, 235U, 237Np and 239Pu are useful for this purpose. A good discussion on neutron detection is found in chapter 14 of the book Radiation Detection and Measurement by Glenn F. Knoll (John Wiley & Sons, 1979).
# Uses
The neutron plays an important role in many nuclear reactions. For example, neutron capture often results in neutron activation, inducing radioactivity. In particular, knowledge of neutrons and their behavior has been important in the development of nuclear reactors and nuclear weapons.
Cold, thermal and hot neutron radiation is commonly employed in neutron scattering facilities, where the radiation is used in a similar way one uses X-rays for the analysis of condensed matter. Neutrons are complementary to the latter in terms of atomic contrasts by different scattering cross sections; sensitivity to magnetism; energy range for inelastic neutron spectroscopy; and deep penetration into matter.
The development of "neutron lenses" based on total internal reflection within hollow glass capillary tubes or by reflection from dimpled aluminum plates has driven ongoing research into neutron microscopy and neutron/gamma ray tomography.[3][4][5]
One use of neutron emitters is the detection of light nuclei, particularly the hydrogen found in water molecules. When a fast neutron collides with a light nucleus, it loses a large fraction of its energy. By measuring the rate at which slow neutrons return to the probe after reflecting off of hydrogen nuclei, a neutron probe may determine the water content in soil.
# Sources
Due to the fact that free neutrons are unstable, they can be obtained only from nuclear disintegrations, nuclear reactions, and high-energy reactions (such as in cosmic radiation showers or accelerator collisions). Free neutron beams are obtained from neutron sources by neutron transport. For access to intense neutron sources, researchers must go to specialist facilities, such as the ISIS facility in the UK, which is currently the world's most intense pulsed neutron and muon source.
Neutrons' lack of total electric charge prevents engineers or experimentalists from being able to steer or accelerate them. Charged particles can be accelerated, decelerated, or deflected by electric or magnetic fields. However, these methods have no effect on neutrons except for a small effect of a magnetic field because of the neutron's magnetic moment.
# Discovery
In 1930 Walther Bothe and H. Becker in Germany found that if the very energetic alpha particles emitted from polonium fell on certain light elements, specifically beryllium, boron, or lithium, an unusually penetrating radiation was produced. At first this radiation was thought to be gamma radiation, although it was more penetrating than any gamma rays known, and the details of experimental results were very difficult to interpret on this basis. The next important contribution was reported in 1932 by Irène Joliot-Curie and Frédéric Joliot in Paris. They showed that if this unknown radiation fell on paraffin or any other hydrogen-containing compound it ejected protons of very high energy. This was not in itself inconsistent with the assumed gamma ray nature of the new radiation, but detailed quantitative analysis of the data became increasingly difficult to reconcile with such a hypothesis. Finally, in 1932 the physicist James Chadwick in England performed a series of experiments showing that the gamma ray hypothesis was untenable. He suggested that in fact the new radiation consisted of uncharged particles of approximately the mass of the proton, and he performed a series of experiments verifying his suggestion. Such uncharged particles were eventually called neutrons, apparently from the Latin root for neutral and the Greek ending -on (by imitation of electron and proton).
# Anti-neutron
The antineutron is the antiparticle of the neutron. It was discovered by Bruce Cork in the year 1956, a year after the antiproton was discovered.
CPT-symmetry puts strong constraints on the relative properties of particles and antiparticles and, therefore, is open to stringent tests. The fractional difference in the masses of the neutron and antineutron is (9±5)×10−5. Since the difference is only about 2 standard deviations away from zero, this does not give any convincing evidence of CPT-violation.[2]
# Current developments
## Electric dipole moment
An experiment at the Institut Laue-Langevin has attempted to measure an electric dipole, or separation of charges, within the neutron, and is consistent with an electric dipole moment of zero. These results are important in developing theories that go beyond the Standard Model, but are inconsistent with it due to the lack of explanation of the fundamental interactions.[6][7]
## Tetraneutrons
The existence of stable clusters of four neutrons, or tetraneutrons, has been hypothesised by a team led by Francisco-Miguel Marqués at the CNRS Laboratory for Nuclear Physics based on observations of the disintegration of beryllium-14 nuclei. This is particularly interesting, because current theory suggests that these clusters should not be stable.
# Protection
Exposure to neutrons can be hazardous, since the interaction of neutrons with molecules in the body can cause disruption to molecules and atoms, and can also cause reactions which give rise to other forms of radiation (such as protons). The normal precautions of radiation protection apply: avoid exposure, stay as far from the source as possible, and keep exposure time to a minimum. Some particular thought must be given to how to protect from neutron exposure, however. For other types of radiation, e.g. alpha particles, beta particles, or gamma rays, material of a high atomic number and with high density make for good shielding; frequently lead is used. However, this approach will not work with neutrons, since the absorption of neutrons does not increase straightforwardly with atomic number, as it does with alpha, beta, and gamma radiation. Instead one needs to look at the particular interactions neutrons have with matter (see the section on detection above). For example, hydrogen rich materials are often used to shield against neutrons, since ordinary hydrogen both scatters and slows neutrons. This often means that simple concrete blocks or even paraffin-loaded plastic blocks afford better protection from neutrons than do far more dense materials. After slowing, neutrons may then be absorbed with an isotope which has high affinity for slow neutrons without causing secondary capture-radiation, such as lithium-6.
Hydrogen-rich ordinary water effects neutron absorption in nuclear fission reactors: usually neutrons are so strongly absorbed by normal water that fuel-enrichement with fissionable isotope, is required. The deuterium in heavy water has a very much lower absorption affinity for neutrons than does protium (normal light hydrogen). Deuterium is therefore used in CANDU-type reactors, in order to slow ("moderate") neutron velocity, so that they are more effective at causing nuclear fission, without capturing them. | https://www.wikidoc.org/index.php/Neutron | |
8d25a7f617be6208ae5a7cd994580b7cf011e3ce | wikidoc | Nicogel | Nicogel
Nicogel™ is a "tobacco gel", applied to skin as a substitute for cigarette use. Nicogel is a tobacco product, and is not a smoking cessation product.
# Usage
Nicogel claims to be a cigarette substitute designed so tobacco users can continue using "tobacco" in a discreet form. Nicogel is sold as 50ml dispensers (containing "50 cigarette-equivalents") and as boxes of individually wrapped, single-use packets (containing either 10 or 120 cigarette-equivalents). Nicogel is "a water soluble gel containing liquefied tobacco."
Because many public places have placed bans on smoking, Nicogel touts itself as a more convenient tobacco product. However Nicogel does
# Consumer Issues
There is concern that this product may deceive consumers, as its name implies that it is a nicotine substitute. However exploration of Nicogel.net contradicts this perception. Furhermore, the product advertises itself as an alternative to smoking but does not ostensibly provide address any of the factors behind cigarette cravings (nicotine withdrawal, oral fixation, etc).
# Health Effects
Nicogel claims that the product has 1/10th of the tobacco of a cigarette. American Cancer Society's director, Thomas J. Glynn, Ph.D., warns that "no independent research has been conducted to validate whether it's effective and safe," and that there is "no indication of toxicity or level of nicotine it delivers."
Nicogel may irritate sensitive skin and cause rashes, allergies, or red and swollen skin. The makers advise pregnant or breast-feeding women to avoid Nicogel, and assert that drinking alcohol in moderation is safe while using Nicogel. | Nicogel
Nicogel™ is a "tobacco gel", applied to skin as a substitute for cigarette use. Nicogel is a tobacco product, and is not a smoking cessation product.
# Usage
Nicogel claims to be a cigarette substitute designed so tobacco users can continue using "tobacco" in a discreet form.[1] Nicogel is sold as 50ml dispensers (containing "50 cigarette-equivalents") and as boxes of individually wrapped, single-use packets (containing either 10 or 120 cigarette-equivalents).[2] Nicogel is "a water soluble gel containing liquefied tobacco."[1]
Because many public places have placed bans on smoking, Nicogel touts itself as a more convenient tobacco product.[2] However Nicogel does
# Consumer Issues
There is concern that this product may deceive consumers[citation needed], as its name implies that it is a nicotine substitute[citation needed]. However exploration of Nicogel.net contradicts this perception[citation needed]. Furhermore, the product advertises itself as an alternative to smoking but does not ostensibly provide address any of the factors behind cigarette cravings (nicotine withdrawal, oral fixation, etc)[citation needed].
# Health Effects
Nicogel claims that the product has 1/10th of the tobacco of a cigarette.[1] American Cancer Society's director, Thomas J. Glynn, Ph.D., warns that "no independent research has been conducted to validate whether it's effective and safe," and that there is "no indication of [the] toxicity or level of nicotine it delivers."[3]
Nicogel may irritate sensitive skin and cause rashes, allergies, or red and swollen skin.[3] The makers advise pregnant or breast-feeding women to avoid Nicogel,[4] and assert that drinking alcohol in moderation is safe while using Nicogel.[5] | https://www.wikidoc.org/index.php/Nicogel | |
826dc6cf64019a435d34142f21d02094eddb0e62 | wikidoc | Nitrate | Nitrate
In inorganic chemistry, a nitrate is a salt of nitric acid with an ion composed of one nitrogen and three oxygen atoms (NO3−). In organic chemistry the esters of nitric acid and various alcohols are called nitrates.
# Chemical properties
The nitrate ion is a polyatomic ion with the empirical formula NO3− and a molecular mass of 62.0049. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identical oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a formal charge of negative one, where each oxygen carries a −2/3 charge while the nitrogen carries a +1 charge, and is commonly used as an example of resonance. The three canonical structures of the nitrate ion are shown resonating below:
Almost all inorganic nitrate salts are soluble in water at standard temperature and pressure.
In organic chemistry a nitrate is a functional group with general chemical formula RONO2 where R stands for any organic residue. They are the esters of nitric acid and alcohols formed by nitroxylation. Examples are methyl nitrate formed by reaction of methanol and nitric acid, the nitrate of tartaric acid, and the inappropriately named nitroglycerin.
# Related materials
Nitrates should not be confused with nitrites (NO2−) the salts of nitrous acid. Organic compounds containing the nitro functional group (which has the same formula and structure as the nitrate ion save that one of the O− atoms is replaced by the R group) are known as nitro compounds.
# Effects on aquatic life
In freshwater or estuarine systems close to land, nitrate can reach high levels that can potentially cause the death of fish. While nitrate is much less toxic than ammonia or nitrite, levels over 30 ppm of nitrate can inhibit growth, impair the immune system and cause stress in some aquatic species. However, in light of inherent problems with past protocols on acute nitrate toxicity experiments, the extent of nitrate toxicity has been the subject of recent debate.
In most cases of excess nitrate concentrations in aquatic systems, the primary source is surface runoff from agricultural or landscaped areas which have received excess nitrate fertilizer. These levels of nitrate can also lead to algae blooms, and when nutrients become limiting (such as potassium, phosphate or nitrate) then eutrophication can occur. As well as leading to water anoxia, these blooms may cause other changes to ecosystem function, favouring some groups of organisms over others. Consequently, as nitrates form a component of total dissolved solids, they are widely used as an indicator of water quality.
Nitrates are also a by-product of septic systems. Specifically, they are a naturally occurring chemical that is left after the break down or decomposition of animal or human waste. Water quality may also be affected through ground water resources that have a high number of septic systems in a watershed. Septics leach down into ground water resources or aquifers and supply near by bodies of water. Lakes that rely on ground water are often affected by nitrification through this process. | Nitrate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In inorganic chemistry, a nitrate is a salt of nitric acid with an ion composed of one nitrogen and three oxygen atoms (NO3−). In organic chemistry the esters of nitric acid and various alcohols are called nitrates.
# Chemical properties
The nitrate ion is a polyatomic ion with the empirical formula NO3− and a molecular mass of 62.0049. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identical oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a formal charge of negative one, where each oxygen carries a −2/3 charge while the nitrogen carries a +1 charge, and is commonly used as an example of resonance. The three canonical structures of the nitrate ion are shown resonating below:
Almost all inorganic nitrate salts are soluble in water at standard temperature and pressure.
In organic chemistry a nitrate is a functional group with general chemical formula RONO2 where R stands for any organic residue. They are the esters of nitric acid and alcohols formed by nitroxylation. Examples are methyl nitrate formed by reaction of methanol and nitric acid,[1] the nitrate of tartaric acid,[2] and the inappropriately named nitroglycerin.
# Related materials
Nitrates should not be confused with nitrites (NO2−) the salts of nitrous acid. Organic compounds containing the nitro functional group (which has the same formula and structure as the nitrate ion save that one of the O− atoms is replaced by the R group) are known as nitro compounds.
# Effects on aquatic life
In freshwater or estuarine systems close to land, nitrate can reach high levels that can potentially cause the death of fish. While nitrate is much less toxic than ammonia or nitrite,[3] levels over 30 ppm of nitrate can inhibit growth, impair the immune system and cause stress in some aquatic species.[citation needed] However, in light of inherent problems with past protocols on acute nitrate toxicity experiments, the extent of nitrate toxicity has been the subject of recent debate.[4]
In most cases of excess nitrate concentrations in aquatic systems, the primary source is surface runoff from agricultural or landscaped areas which have received excess nitrate fertilizer. These levels of nitrate can also lead to algae blooms, and when nutrients become limiting (such as potassium, phosphate or nitrate) then eutrophication can occur. As well as leading to water anoxia, these blooms may cause other changes to ecosystem function, favouring some groups of organisms over others. Consequently, as nitrates form a component of total dissolved solids, they are widely used as an indicator of water quality.
Nitrates are also a by-product of septic systems. Specifically, they are a naturally occurring chemical that is left after the break down or decomposition of animal or human waste. Water quality may also be affected through ground water resources that have a high number of septic systems in a watershed. Septics leach down into ground water resources or aquifers and supply near by bodies of water. Lakes that rely on ground water are often affected by nitrification through this process. | https://www.wikidoc.org/index.php/Nitrate | |
c8e6a64244a1f0bb3f36973dbc34c15aa0c620a8 | wikidoc | Nitrene | Nitrene
In chemistry, a nitrene (R-N:) is the nitrogen analogue of a carbene. The nitrogen atom has only 6 electrons available and is therefore considered an electrophile. A nitrene is a reactive intermediate and is involved is many chemical reactions .
# Electron configuration
In the most simple nitrene linear imidogene (:N-H) two of the 6 available electrons form a covalent bond with hydrogen, two other create a free electron pair and the two remaining electrons occupy two degenerate p-orbitals. Consistent with Hund's rule the low energy form of imidogene is a triplet with one electron for each orbital and the high energy form is the singlet state with an electron pair in one filled orbital and one empty orbital.
As with carbenes, a strong correlation exists between the spin density on the nitrogen atom which can be calculated in silico and the zero-field splitting parameter D which can be derived experimentally from electron spin resonance . Small nitrenes such as NH or CF3N have D values around 1.8 cm-1 with spin densities close to a maximum value of 2. At the lower end of the scale are molecules with low D (< 0.4) values and spin density of 1.2 to 1-4 such as 9-anthrylnitrene and 9-phenanthryl.
# Formation
Nitrenes are very reactive and not isolated as such. They are formed as reactive intermediates in the reactions:
- from thermolysis or photolysis of azides with expulsion of nitrogen gas, analogues to the formation of carbenes from diazo compounds.
- from isocyanates, with expulsion of carbon monoxide, analogues to carbene formation from ketenes
# Reactions
Nitrenes reactions are:
- nitrene C-H insertion. A nitrene can easily insert into a carbon to hydrogen covalent bond yielding an amine or amide. A singlet nitrene reacts with retention of configuration. In one study a nitrene, formed by oxidation of a carbamate with potassium persulfate, gives an insertion reaction into the palladium to nitrogen bond of the reaction product of palladium(II) acetate with 2-phenylpyridine to Methyl N-(2-pyridylphenyl)carbamate in a cascade reaction:
- nitrene cycloaddition. With alkenes, nitrenes react to aziridines, very often with nitrenoid precursors such as sulfonyliminoiodinanes (PhI=NT) but the reaction is known to work directly with the sulfonamide in presence of a gold catalyst :
- arylnitrene ring-expansion and ring-contraction. Aryl nitrenes show ring expansion to 7-membered ring cumulenes, ring opening reactions and nitrile formations many times in complex reaction paths. For instance the azide 2 in the scheme sketched below trapped in an argon matrix at 20 K on photolysis expels nitrogen to the triplet nitrene 4 (observed experimentally with ESR and ultraviolet-visible spectroscopy) which is in equilibrium with the ring-expansion product 6. | Nitrene
In chemistry, a nitrene (R-N:) is the nitrogen analogue of a carbene. The nitrogen atom has only 6 electrons available and is therefore considered an electrophile. A nitrene is a reactive intermediate and is involved is many chemical reactions [1] [2].
# Electron configuration
In the most simple nitrene linear imidogene (:N-H) two of the 6 available electrons form a covalent bond with hydrogen, two other create a free electron pair and the two remaining electrons occupy two degenerate p-orbitals. Consistent with Hund's rule the low energy form of imidogene is a triplet with one electron for each orbital and the high energy form is the singlet state with an electron pair in one filled orbital and one empty orbital.
As with carbenes, a strong correlation exists between the spin density on the nitrogen atom which can be calculated in silico and the zero-field splitting parameter D which can be derived experimentally from electron spin resonance [3]. Small nitrenes such as NH or CF3N have D values around 1.8 cm-1 with spin densities close to a maximum value of 2. At the lower end of the scale are molecules with low D (< 0.4) values and spin density of 1.2 to 1-4 such as 9-anthrylnitrene and 9-phenanthryl.
# Formation
Nitrenes are very reactive and not isolated as such. They are formed as reactive intermediates in the reactions:
- from thermolysis or photolysis of azides with expulsion of nitrogen gas, analogues to the formation of carbenes from diazo compounds.
- from isocyanates, with expulsion of carbon monoxide, analogues to carbene formation from ketenes
# Reactions
Nitrenes reactions are:
- nitrene C-H insertion. A nitrene can easily insert into a carbon to hydrogen covalent bond yielding an amine or amide. A singlet nitrene reacts with retention of configuration. In one study [4] a nitrene, formed by oxidation of a carbamate with potassium persulfate, gives an insertion reaction into the palladium to nitrogen bond of the reaction product of palladium(II) acetate with 2-phenylpyridine to Methyl N-(2-pyridylphenyl)carbamate in a cascade reaction:
- nitrene cycloaddition. With alkenes, nitrenes react to aziridines, very often with nitrenoid precursors such as sulfonyliminoiodinanes (PhI=NT) but the reaction is known to work directly with the sulfonamide in presence of a gold catalyst [6] [7]:
- arylnitrene ring-expansion and ring-contraction. Aryl nitrenes show ring expansion to 7-membered ring cumulenes, ring opening reactions and nitrile formations many times in complex reaction paths. For instance the azide 2 in the scheme sketched below [3] trapped in an argon matrix at 20 K on photolysis expels nitrogen to the triplet nitrene 4 (observed experimentally with ESR and ultraviolet-visible spectroscopy) which is in equilibrium with the ring-expansion product 6. | https://www.wikidoc.org/index.php/Nitrene | |
42af1a8dc9b2827908aaeb73544ad5f675436a98 | wikidoc | Nitride | Nitride
In chemistry a nitride is a compound of nitrogen with a less electronegative element where nitrogen has an oxidation state of -3. Note that there are exceptions to this naming convention, the nitrides of hydrogen, NH3 and carbon, (CN)2, are called ammonia and cyanogen respectively and that the nitrides of bromine, iodine are called nitrogen tribromide and nitrogen triiodide. Note that nitrogen also forms pernitrides, that contain N22− and azides, that contain N3−.
Nitrogen has one of the highest electronegativities, only oxygen, fluorine and chlorine are higher. This means that the nitrides are a very large group of compounds. They have wide range of properties and applications.
- refractory materials e.g.
- lubricant e.g. hexagonal boron nitride, BN
- cutting materials e.g. silicon nitride, Si3N4
- insulators e.g. boron nitride, BN, silicon nitride, Si3N4
- semiconductors e.g. gallium nitride, GaN
- metal coatings e.g. titanium nitride, TiN
- hydrogen storage e.g Lithium nitride, Li3N
Classification of such a varied group of compounds is necessarily arbitrary. The following is based around their structure:
- salt like, e.g. lithium nitride, Li3N, beryllium nitride, Be3N2
- covalent
3 dimensional structures e.g. phosphorus nitride, P3N5; boron nitride, BN
diamond like e.g. gallium nitride, GaN
molecular ("volatile") e.g. tetrasulfur tetranitride, S4N4
- 3 dimensional structures e.g. phosphorus nitride, P3N5; boron nitride, BN
- diamond like e.g. gallium nitride, GaN
- molecular ("volatile") e.g. tetrasulfur tetranitride, S4N4
- interstitial e.g. titanium nitride, TiN
- intermediate e.g. iron nitride, Fe2N
## Nitride ion
The nitride ion is N3− (a nitrogen atom plus three electrons). The extra electrons give the nitrogen atom a closed inert gas shell. The nitride ion is isoelectronic with the oxide anion, O2−, and the fluoride anion, F− and has an ionic radius estimated to be 140 pm. The nitride ion is a strong π-donor ligand, stronger than O2−. It forms nitrido complexes which have a short metal nitrogen bond length indicating multiple bonding.
## Salt like nitrides
The salt like nitrides are formed by:
- the alkali metals, Li3N, Na3N and K3N. Li3N is readily formed and has a unique structure. Na3N and K3N have been synthesised by simultaneously depositing metal atoms and nitrogen atoms onto a liquid nitrogen cooled sapphire substrate. Both are unstable compounds.
- the alkaline earth metals Mg3N2, Be3N2 and Ca3N2
- the group 3 metals e.g. scandium nitride, ScN
- the group 11 metals e.g. copper nitride, Cu3N
- the group 12 metals e.g. Zn3N2
Lithium nitride and the alkaline earth nitrides deprotonate hydrogen gas, and are rapidly hydrolysed by water to form ammonia.
## Covalent nitrides
## Interstitial nitrides
The interstitial nitrides are formed by transition metals where there is a sufficient difference in size between the metal atom and the nitrogen to allow the host metal lattice to accommodate the nitrogen atom. This condition is true for the group 4, 5 and 6 transition metals i.e. the Titanium, Vanadium and Chromium groups. The group 4 and 5 nitrides are refractory i.e. high melting and chemically stable.
## Intermediate nitrides
Group 7 and 8 transition metals form nitrides that decompose readily e.g iron nitride, Fe2N melts with decomposition at 200oC. The precious metals are currently being investigated by a number of researchers and thin films of platinum, gold and osmium nitrides have been produced. However there is some discussion as to their structures and their properties. Platinum nitride and osmium nitride for example are now believed to contain N2 units and as such should not be called nitrides.
# General references
- WebElements
- Template:Greenwood&Earnshaw
- H.O Pierson (1996). Handbook of refractory carbides and nitrides, William Andrew Inc. ISBN 0-8155-1392-5
# Footnotes
- ↑ Synthesis and structure of Na3N, Fischer, D., Jansen, M. Angew Chem Intnl 41, 10, 1755 (2002) DOI:10.1002/1521-3773(20020517)41:103.0.CO;2-C
- ↑ Synthesis and structure of K3N, Fischer, D.; Cancarevic, Z.; Schön, J. C.; Jansen, M. Z. fur anorg allgem Chemie, 630, 1, 156, DOI: 10.1002/zaac.200300280
- ↑ Gold film with gold nitride-A conductor but harder than gold, L. Siller, N. Peltekis, S. Krishnamurthy, Y. Chao, S.J. Bull, M.R.C. Hunt, Appl. Phys. Lett. 86, 22, 221912, (2005) DOI: 10.1063/1.1941471
- ↑ OsN2: Crystal structure and electronic properties, J. A. Montoya, A.D Hernandez, C. Sanloup, E Gregoryanz, S Scandolo, Appl. Phys. Lett. 90, 1, 011909 (2007) DOI: 10.1063/1.2430631
de:Nitride
et:Nitriidid
nl:Nitride
uk:Нітриди | Nitride
In chemistry a nitride is a compound of nitrogen with a less electronegative element where nitrogen has an oxidation state of -3. Note that there are exceptions to this naming convention, the nitrides of hydrogen, NH3 and carbon, (CN)2, are called ammonia and cyanogen respectively and that the nitrides of bromine, iodine are called nitrogen tribromide and nitrogen triiodide. Note that nitrogen also forms pernitrides, that contain N22− and azides, that contain N3−.
Nitrogen has one of the highest electronegativities, only oxygen, fluorine and chlorine are higher. This means that the nitrides are a very large group of compounds. They have wide range of properties and applications.
- refractory materials e.g.
- lubricant e.g. hexagonal boron nitride, BN
- cutting materials e.g. silicon nitride, Si3N4
- insulators e.g. boron nitride, BN, silicon nitride, Si3N4
- semiconductors e.g. gallium nitride, GaN
- metal coatings e.g. titanium nitride, TiN
- hydrogen storage e.g Lithium nitride, Li3N
Classification of such a varied group of compounds is necessarily arbitrary. The following is based around their structure:
- salt like, e.g. lithium nitride, Li3N, beryllium nitride, Be3N2
- covalent
3 dimensional structures e.g. phosphorus nitride, P3N5; boron nitride, BN
diamond like e.g. gallium nitride, GaN
molecular ("volatile") e.g. tetrasulfur tetranitride, S4N4
- 3 dimensional structures e.g. phosphorus nitride, P3N5; boron nitride, BN
- diamond like e.g. gallium nitride, GaN
- molecular ("volatile") e.g. tetrasulfur tetranitride, S4N4
- interstitial e.g. titanium nitride, TiN
- intermediate e.g. iron nitride, Fe2N
## Nitride ion
The nitride ion is N3− (a nitrogen atom plus three electrons). The extra electrons give the nitrogen atom a closed inert gas shell. The nitride ion is isoelectronic with the oxide anion, O2−, and the fluoride anion, F− and has an ionic radius estimated to be 140 pm. The nitride ion is a strong π-donor ligand, stronger than O2−. It forms nitrido complexes which have a short metal nitrogen bond length indicating multiple bonding.
## Salt like nitrides
The salt like nitrides are formed by:
- the alkali metals, Li3N, Na3N and K3N. Li3N is readily formed and has a unique structure. Na3N [1] and K3N [2] have been synthesised by simultaneously depositing metal atoms and nitrogen atoms onto a liquid nitrogen cooled sapphire substrate. Both are unstable compounds.
- the alkaline earth metals Mg3N2, Be3N2 and Ca3N2
- the group 3 metals e.g. scandium nitride, ScN
- the group 11 metals e.g. copper nitride, Cu3N
- the group 12 metals e.g. Zn3N2
Lithium nitride and the alkaline earth nitrides deprotonate hydrogen gas, and are rapidly hydrolysed by water to form ammonia.
## Covalent nitrides
## Interstitial nitrides
The interstitial nitrides are formed by transition metals where there is a sufficient difference in size between the metal atom and the nitrogen to allow the host metal lattice to accommodate the nitrogen atom. This condition is true for the group 4, 5 and 6 transition metals i.e. the Titanium, Vanadium and Chromium groups. The group 4 and 5 nitrides are refractory i.e. high melting and chemically stable.
## Intermediate nitrides
Group 7 and 8 transition metals form nitrides that decompose readily e.g iron nitride, Fe2N melts with decomposition at 200oC. The precious metals are currently being investigated by a number of researchers and thin films of platinum, gold and osmium nitrides have been produced. However there is some discussion as to their structures and their properties. Platinum nitride and osmium nitride for example are now believed to contain N2 units and as such should not be called nitrides.
[3]
[4]
# General references
- WebElements
- Template:Greenwood&Earnshaw
- H.O Pierson (1996). Handbook of refractory carbides and nitrides, William Andrew Inc. ISBN 0-8155-1392-5
# Footnotes
- ↑ Synthesis and structure of Na3N, Fischer, D., Jansen, M. Angew Chem Intnl 41, 10, 1755 (2002) DOI:10.1002/1521-3773(20020517)41:10<1755::AID-ANIE1755>3.0.CO;2-C
- ↑ Synthesis and structure of K3N, Fischer, D.; Cancarevic, Z.; Schön, J. C.; Jansen, M. Z. fur anorg allgem Chemie, 630, 1, 156, DOI: 10.1002/zaac.200300280
- ↑ Gold film with gold nitride-A conductor but harder than gold, L. Siller, N. Peltekis, S. Krishnamurthy, Y. Chao, S.J. Bull, M.R.C. Hunt, Appl. Phys. Lett. 86, 22, 221912, (2005) DOI: 10.1063/1.1941471
- ↑ OsN2: Crystal structure and electronic properties, J. A. Montoya, A.D Hernandez, C. Sanloup, E Gregoryanz, S Scandolo, Appl. Phys. Lett. 90, 1, 011909 (2007) DOI: 10.1063/1.2430631
de:Nitride
et:Nitriidid
nl:Nitride
uk:Нітриди
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Nitride | |
66f46f7a99f2ff3081786b2d5f6a2030944ae45d | wikidoc | Poppers | Poppers
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Poppers is a slang term for various alkyl nitrites inhaled for recreational purposes, particularly amyl nitrite, butyl nitrite, isopropyl nitrite and isobutyl nitrite. Amyl nitrite is used medically as an antidote to cyanide poisoning, but the term "poppers" refers specifically to recreational use. Amyl nitrite and several other alkyl nitrites, which are present in products such as air freshener and video head cleaner, are often inhaled with the goal of enhancing sexual pleasure. These products have also been part of the club culture from the 1970s disco scene to the 1980s and 1990s rave scene. Poppers have a long history of use due to the rush of warm sensations and dizziness experienced when the vapours are inhaled.
Although, according to at least one analysis, poppers have a lower risk of harm to society and the individual than do certain other recreational drugs, other cases have shown that serious adverse effects can occur. In a letter to the New England Journal of Medicine, an ophthalmologist described four cases in which recreational users of poppers experienced temporary changes in vision. There is some evidence to indicate that even occasional use of poppers may affect vision. With heavy long-term use there is a potential for neurological damage. Accidentally swallowing or aspirating the liquid, rather than inhaling the vapours, is certainly dangerous and can prove fatal.
# History
Sir Thomas Lauder Brunton (March 14, 1844–September 16, 1916), a Scottish physician, famously pioneered the use of amyl nitrite to treat angina pectoris. Brunton's clinical use of amyl nitrite to treat angina was inspired by earlier work with the same reagent by Arthur Gamgee and Benjamin Ward Richardson. Brunton reasoned that the pain and discomfort of angina could be reduced by administering amyl nitrite to dilate the coronary arteries of patients, thus improving blood flow to the heart muscle.
In addition, the light alkyl nitrites cause the formation of methemoglobin wherein, as an effective antidote to cyanide poisoning, the methemoglobin combines with the cyanide to form nontoxic cyanmethemoglobin. First responders typically carry a cyanide poison kit containing amyl nitrite, such as the popular Taylor Pharmaceutical Cyanide Antidote Kit.
TIME and the Wall Street Journal reported that the popper fad began among homosexual men as a way to enhance sexual pleasure, but "quickly spread to avant-garde heterosexuals" as a result of aggressive marketing. A series of interviews conducted in the late 1970s revealed a wide spectrum of users, including construction workers, a "trendy East Side NYC couple" at a "chic NYC nightclub", a Los Angeles businesswoman "in the middle of a particularly hectic public-relations job" (who confided to the reporter that "I could really use a popper now"), and frenetic disco dancers amid "flashing strobe lights and the pulsating beat of music in discos across the country."
User surveys are hard to come by, but a 1988 study found that 69% of men who had sex with men in the Baltimore/Washington DC area reported they had used poppers, with 21% having done so in the prior year. The survey also found that 11% of recreational drug users in the area reported using poppers, increasing to 22% among "heavy abusers," with an average age of first use of 25.6 years old. Both survey groups used poppers to "get high," but the men that had sex with men were more likely to use them during sex. It was reported that this group reduced usage following the AIDS epidemic, while the drug-users had not. A 1987 study commissioned by the US Senate and conducted by the Department of Health and Human Services found that less than 3% of the overall population had ever used poppers.
Use by minors is historically minimal due, in part, to the ban on sales to minors by major manufacturers for public relations reasons and because some jurisdictions regulate sales to minors by statute. A paper published in 2005 examined use of poppers self-reported by adolescents aged 12–17 in the (American) 2000 and 2001 National Household Surveys on Drug Abuse. In all, 1.5% of the respondents in this age group reported having used poppers. This figure rose to 1.8% in those over 14. Living in nonmetropolitan areas, having used mental health services in the past year (for purposes unconnected with substance use treatment), the presence of delinquent behaviours, past year alcohol and drug abuse and dependence, and multi-drug use were all associated with reporting the use of poppers. In contrast to these low rates, a survey in the North West of England found a rate of 20% self-reported use of poppers among 16-year-olds.
Originally marketed as a prescription drug in 1937, amyl nitrite remained so until 1960, when the Food and Drug Administration removed the prescription requirement due to its safety record. This requirement was reinstated in 1969, after observation of an increase in recreational use.
Other alkyl nitrites were outlawed in the USA by Congress through the Anti-Drug Abuse Act of 1988. The law includes an exception for commercial purposes. The term commercial purpose is defined to mean any use other than for the production of consumer products containing volatile alkyl nitrites meant for inhaling or otherwise introducing volatile alkyl nitrites into the human body for euphoric or physical effects. The law came into effect in 1990. Visits to retail outlets selling these products reveal that some manufacturers have since reformulated their products to abide by the regulations, through the use of the legal cyclohexyl nitrite as the primary ingredient in their products, which are sold as video head cleaners, polish removers, or room odorants.
Amyl nitrite, manufactured by Burroughs Wellcome (now GlaxoSmithKline) and Eli Lilly and Company, was originally sold in small glass ampoules that were crushed to release their vapors, and received the name "poppers" as a result of the popping sound made by crushing the ampule. Today, reformulated poppers containing isobutyl nitrite are sold under brand names such as RUSH, Locker Room, Snappers, and Liquid Gold. Many different brands exist and are sold in different localities.
# Effects
Inhaling nitrites relaxes smooth muscles throughout the body, including the sphincter muscles of the anus and the vagina. It is unclear if there is a direct effect on the brain. Smooth muscle surrounds the body's blood vessels and when relaxed causes these vessels to dilate resulting in an immediate increase in heart rate and blood flow throughout the body, producing a sensation of heat and excitement that usually lasts for a couple of minutes.
Alkyl nitrites are often used as a club drug or to enhance a sexual experience. The head rush, euphoria, and other sensations that result from the increased heart rate are often felt to increase sexual arousal and desire. It is widely reported that poppers can enhance and prolong orgasms.
While anecdotal evidence reveals that both men and women can find the experience of using poppers pleasurable, this experience is not universal; some men report that poppers can cause short-term erectile problems.
# Health issues
Acute intake of poppers may cause asphyxia, arrhythmias, cardiovascular depression, carbon monoxide poisoning, hepatorenal toxicity, methemoglobinemia, neurologic dysfunction, mucosal, pulmonary, skin irritation and facial dermatitis. With chronic use neurological damage may occur. Swallowing alkyl nitrites can cause serious acute medical complications and may result in death. Accidental aspiration of amyl or butyl nitrites may lead to the development of lipoid pneumonia.
Poppers can interact with other vasodilators, such as sildenafil (Viagra), to cause a serious decrease in blood pressure, leading to fainting, stroke, or even heart attack.
Poppers can also increase intraocular pressure, resulting in glaucoma. In reference to vision loss, a published case concluded "No similar cases have been described in the more than 100-year history of pharmacological use of amyl nitrite for angina pectoris, and pharmacologically it is hard to point out a rationale behind the sequential visual loss." In October, 2010, Dr. Michel Paques at the Quinze-Vingts National Hospital in Paris, France reported that at least some people may suffer permanent or temporary eye damage from the use of poppers—even when the poppers are used only once—in a letter to the New England Journal of Medicine. The significance of these isolated observations remains uncertain.
Rarely, the use of poppers can cause methemoglobinemia and hemolysis, especially in individuals predisposed towards such a condition or in overdose. An overdose via ingestion (rather than inhalation) may result in cyanosis, unconsciousness, coma and even death. Methylene blue is a treatment for methemoglobinemia associated with popper use. Other risks include burns if spilled on skin, loss of consciousness, headaches, and red or itching rashes around the mouth and nose.
The Merck Manual of Diagnosis and Therapy reports that there is little evidence of significant hazard associated with inhalation of alkyl nitrites. A study and ranking of drugs for harmfulness devised by British-government advisers and based upon scientific evidence of harm to both individuals and society showed that poppers pose little potential harm to individuals or to society when compared to other recreational drugs. A 1983 U. S. Consumer Product Safety Commission investigation Briefing Package stated that "Available injury data did not indicate a significant risk of personal injury or illness from room odorizer abuse."
## Association with AIDS epidemic
It has been suggested that poppers have been related to AIDS, HIV infection, and the AIDS-related cancer Kaposi's sarcoma. Initially poppers were considered as a hypothesis for the then-burgeoning AIDS epidemic, and the idea has persisted in large part due to the activities of AIDS denialists as a pseudoscientific rationalization for the presence of AIDS in homosexual males. Animal studies have suggested an association between alkyl nitrites and Kaposi's sarcoma, a type of skin cancer associated with HIV-positive individuals, though a study of the use of poppers by HIV positive men did not support biological link between the two. Instead it has been suggested the correlation was based on a bias among some popper users towards high-risk sexual behaviours. In a 1986–1988 series of study reviews and technical workshops with leading authorities, mandated by the US Congress, it was concluded that nitrites are not a causal factor in AIDS infection or Kaposi's sarcoma. A study that followed 715 gay men for eight and a half years published in the Lancet in 1993 rejected any causal relationship between AIDS and poppers. Although the study did conclude an association between the use of poppers in the gay culture and contracting the HIV virus, it also concluded an association between anal sex and contracting the HIV virus. Citing this link, health authorities in some areas of the United States have mandated point of sale warnings on poppers.
Because of possible alterations to the immune system, it has been suggested that HIV positive individuals may face extra health risks from the use of poppers.
# Chemistry
Poppers are a class of chemicals called alkyl nitrites. These are chemical compounds of structure R–ONO. In more formal terms, they are alkyl esters of nitrous acid.
The first few members of the series are volatile liquids; methyl nitrite and ethyl nitrite are gaseous at room temperature and pressure.
Organic nitrites are prepared from alcohols and sodium nitrite in sulfuric acid solution. They decompose slowly on standing, the decomposition products being oxides of nitrogen, water, the alcohol, and polymerization products of the aldehyde.
Physical and Chemical Properties (Sutton, 1963): | Poppers
Please Take Over This Page and Apply to be 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 [2] 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.
Poppers is a slang term for various alkyl nitrites inhaled for recreational purposes, particularly amyl nitrite, butyl nitrite, isopropyl nitrite and isobutyl nitrite.[1][2] Amyl nitrite is used medically as an antidote to cyanide poisoning,[3] but the term "poppers" refers specifically to recreational use. Amyl nitrite and several other alkyl nitrites, which are present in products such as air freshener and video head cleaner[citation needed], are often inhaled with the goal of enhancing sexual pleasure.[4] These products have also been part of the club culture from the 1970s disco scene to the 1980s and 1990s rave scene.[5] Poppers have a long history of use due to the rush of warm sensations and dizziness experienced when the vapours are inhaled.
Although, according to at least one analysis, poppers have a lower risk of harm to society and the individual than do certain other recreational drugs,[6] other cases have shown that serious adverse effects can occur. In a letter to the New England Journal of Medicine, an ophthalmologist described four cases in which recreational users of poppers experienced temporary changes in vision.[7] There is some evidence to indicate that even occasional use of poppers may affect vision.[8] With heavy long-term use there is a potential for neurological damage.[9] Accidentally swallowing or aspirating the liquid, rather than inhaling the vapours, is certainly dangerous and can prove fatal.[10][11]
# History
Sir Thomas Lauder Brunton (March 14, 1844–September 16, 1916), a Scottish physician, famously pioneered the use of amyl nitrite to treat angina pectoris. Brunton's clinical use of amyl nitrite to treat angina was inspired by earlier work with the same reagent by Arthur Gamgee and Benjamin Ward Richardson. Brunton reasoned that the pain and discomfort of angina could be reduced by administering amyl nitrite to dilate the coronary arteries of patients, thus improving blood flow to the heart muscle.
In addition, the light alkyl nitrites cause the formation of methemoglobin wherein, as an effective antidote to cyanide poisoning, the methemoglobin combines with the cyanide to form nontoxic cyanmethemoglobin.[12] First responders typically carry a cyanide poison kit containing amyl nitrite, such as the popular Taylor Pharmaceutical Cyanide Antidote Kit.[13]
TIME and the Wall Street Journal reported that the popper fad began among homosexual men as a way to enhance sexual pleasure, but "quickly spread to avant-garde heterosexuals" as a result of aggressive marketing. A series of interviews conducted in the late 1970s revealed a wide spectrum of users, including construction workers, a "trendy East Side NYC couple" at a "chic NYC nightclub", a Los Angeles businesswoman "in the middle of a particularly hectic public-relations job" (who confided to the reporter that "I could really use a popper now"), and frenetic disco dancers amid "flashing strobe lights and the pulsating beat of music in discos across the country."[14]
User surveys are hard to come by, but a 1988 study found that 69% of men who had sex with men in the Baltimore/Washington DC area reported they had used poppers, with 21% having done so in the prior year. The survey also found that 11% of recreational drug users in the area reported using poppers, increasing to 22% among "heavy abusers," with an average age of first use of 25.6 years old. Both survey groups used poppers to "get high," but the men that had sex with men were more likely to use them during sex. It was reported that this group reduced usage following the AIDS epidemic, while the drug-users had not.[15] A 1987 study commissioned by the US Senate and conducted by the Department of Health and Human Services found that less than 3% of the overall population had ever used poppers.[16]
Use by minors is historically minimal due, in part, to the ban on sales to minors by major manufacturers for public relations reasons and because some jurisdictions regulate sales to minors by statute.[17] A paper published in 2005 examined use of poppers self-reported by adolescents aged 12–17 in the (American) 2000 and 2001 National Household Surveys on Drug Abuse. In all, 1.5% of the respondents in this age group reported having used poppers. This figure rose to 1.8% in those over 14. Living in nonmetropolitan areas, having used mental health services in the past year (for purposes unconnected with substance use treatment), the presence of delinquent behaviours, past year alcohol and drug abuse and dependence, and multi-drug use were all associated with reporting the use of poppers.[18] In contrast to these low rates, a survey in the North West of England found a rate of 20% self-reported use of poppers among 16-year-olds.[5]
Originally marketed as a prescription drug in 1937, amyl nitrite remained so until 1960, when the Food and Drug Administration removed the prescription requirement due to its safety record. This requirement was reinstated in 1969, after observation of an increase in recreational use.
Other alkyl nitrites were outlawed in the USA by Congress through the Anti-Drug Abuse Act of 1988. The law includes an exception for commercial purposes. The term commercial purpose is defined to mean any use other than for the production of consumer products containing volatile alkyl nitrites meant for inhaling or otherwise introducing volatile alkyl nitrites into the human body for euphoric or physical effects.[19] The law came into effect in 1990. Visits to retail outlets selling these products reveal that some manufacturers have since reformulated their products to abide by the regulations, through the use of the legal cyclohexyl nitrite as the primary ingredient in their products, which are sold as video head cleaners, polish removers, or room odorants.
Amyl nitrite, manufactured by Burroughs Wellcome (now GlaxoSmithKline) and Eli Lilly and Company, was originally sold in small glass ampoules that were crushed to release their vapors, and received the name "poppers" as a result of the popping sound made by crushing the ampule.[20] Today, reformulated poppers containing isobutyl nitrite are sold under brand names such as RUSH,[2][4] Locker Room,[2][4] Snappers,[2][21] and Liquid Gold.[1][2] Many different brands exist and are sold in different localities.
# Effects
Inhaling nitrites relaxes smooth muscles throughout the body, including the sphincter muscles of the anus and the vagina.[3] It is unclear if there is a direct effect on the brain.[22] Smooth muscle surrounds the body's blood vessels and when relaxed causes these vessels to dilate resulting in an immediate increase in heart rate and blood flow throughout the body, producing a sensation of heat and excitement that usually lasts for a couple of minutes.[23]
Alkyl nitrites are often used as a club drug or to enhance a sexual experience.[4] The head rush, euphoria, and other sensations that result from the increased heart rate are often felt to increase sexual arousal and desire.[4] It is widely reported that poppers can enhance and prolong orgasms.[1]
While anecdotal evidence reveals that both men and women can find the experience of using poppers pleasurable, this experience is not universal;[24] some men report that poppers can cause short-term erectile problems.[1]
# Health issues
Acute intake of poppers may cause asphyxia, arrhythmias, cardiovascular depression, carbon monoxide poisoning, hepatorenal toxicity, methemoglobinemia, neurologic dysfunction, mucosal, pulmonary, skin irritation and facial dermatitis. With chronic use neurological damage may occur.[9][25] Swallowing alkyl nitrites can cause serious acute medical complications and may result in death.[10] Accidental aspiration of amyl or butyl nitrites may lead to the development of lipoid pneumonia.[11]
Poppers can interact with other vasodilators, such as sildenafil (Viagra), to cause a serious decrease in blood pressure, leading to fainting, stroke, or even heart attack.[26][27][28]
Poppers can also increase intraocular pressure, resulting in glaucoma.[29][30] In reference to vision loss, a published case concluded "No similar cases have been described in the more than 100-year history of pharmacological use of amyl nitrite for angina pectoris, and pharmacologically it is hard to point out a rationale behind the sequential visual loss."[31][32] In October, 2010, Dr. Michel Paques at the Quinze-Vingts National Hospital in Paris, France reported that at least some people may suffer permanent or temporary eye damage from the use of poppers—even when the poppers are used only once—in a letter to the New England Journal of Medicine.[8] The significance of these isolated observations remains uncertain.
Rarely, the use of poppers can cause methemoglobinemia and hemolysis, especially in individuals predisposed towards such a condition or in overdose. An overdose via ingestion (rather than inhalation) may result in cyanosis, unconsciousness, coma and even death. Methylene blue is a treatment for methemoglobinemia associated with popper use.[3][33][34][35] Other risks include burns if spilled on skin, loss of consciousness, headaches,[1][36] and red or itching rashes around the mouth and nose.
The Merck Manual of Diagnosis and Therapy reports that there is little evidence of significant hazard associated with inhalation of alkyl nitrites.[4] A study and ranking of drugs for harmfulness devised by British-government advisers and based upon scientific evidence of harm to both individuals and society showed that poppers pose little potential harm to individuals or to society when compared to other recreational drugs.[6] A 1983 U. S. Consumer Product Safety Commission investigation Briefing Package stated that "Available injury data did not indicate a significant risk of personal injury or illness from room odorizer abuse."[37]
## Association with AIDS epidemic
It has been suggested that poppers have been related to AIDS, HIV infection, and the AIDS-related cancer Kaposi's sarcoma.[38] Initially poppers were considered as a hypothesis for the then-burgeoning AIDS epidemic, and the idea has persisted in large part due to the activities of AIDS denialists as a pseudoscientific rationalization for the presence of AIDS in homosexual males.[39] Animal studies have suggested an association between alkyl nitrites and Kaposi's sarcoma, a type of skin cancer associated with HIV-positive individuals,[40][41] though a study of the use of poppers by HIV positive men did not support biological link between the two.[42] Instead it has been suggested the correlation was based on a bias among some popper users towards high-risk sexual behaviours.[43][44] In a 1986–1988 series of study reviews and technical workshops with leading authorities, mandated by the US Congress, it was concluded that nitrites are not a causal factor in AIDS infection or Kaposi's sarcoma.[16] A study that followed 715 gay men for eight and a half years published in the Lancet in 1993 rejected any causal relationship between AIDS and poppers.[45] Although the study did conclude an association between the use of poppers in the gay culture and contracting the HIV virus, it also concluded an association between anal sex and contracting the HIV virus. Citing this link, health authorities in some areas of the United States have mandated point of sale warnings on poppers.[46]
Because of possible alterations to the immune system, it has been suggested that HIV positive individuals may face extra health risks from the use of poppers.[47]
# Chemistry
Poppers are a class of chemicals called alkyl nitrites. These are chemical compounds of structure R–ONO. In more formal terms, they are alkyl esters of nitrous acid.
The first few members of the series are volatile liquids; methyl nitrite and ethyl nitrite are gaseous at room temperature and pressure.
Organic nitrites are prepared from alcohols and sodium nitrite in sulfuric acid solution. They decompose slowly on standing, the decomposition products being oxides of nitrogen, water, the alcohol, and polymerization products of the aldehyde.
Physical and Chemical Properties (Sutton, 1963): | https://www.wikidoc.org/index.php/Nitrite_inhalants | |
ca4061c234872ea91225fd6aea164d55d3f24084 | wikidoc | Placebo | Placebo
Placebo effect is the term applied by medical science to the therapeutic and healing effects of inert medicines and/or ritualistic or faith healing practices. When referring to medicines, a placebo is a preparation which is pharmacologically inert but which may have a therapeutic effect based solely on the power of suggestion. It may be administered in any of the ways in which pharmaceutical products are administered.
Sometimes known as non-specific effects or subject-expectancy effects, a placebo effect (or its counterpart, the nocebo effect), occurs when a patient's symptoms are altered in some way (i.e., alleviated or exacerbated) by an otherwise inert treatment, due to the individual expecting or believing that it will work.
The placebo effect occurs when a patient takes an inert substance (sometimes called a "sugar pill") in conjunction with the suggestion from an authority figure or from acquired information that the pill will aid in healing and the patient’s condition improves. This effect has been known since the early 20th century.
The word "placebo" has been used in many somewhat varying meanings; see below.
# Concept
Studies published in Proceedings of the National Academy of Sciences using advances in neuroscience (PET scans) have shown that placebos can noticeably reduce pain in humans. Researchers at Columbia and Michigan University have shown that the brains of volunteers who believed that what they were taking was pain medication were shown to be spontaneously releasing opioids, or natural pain relief. According to that ABC report the Food and Drug Administration contends that as many as 75 percent of patients have had responses to sugar pills. It pointed out that all major clinical trials use placebo groups because the effect is significant and to be expected.
This effect has been known since the early 20th century. Generally, one third of a control group taking a placebo shows improvement, and Harvard’s Herbert Benson says that the placebo effect yields beneficial clinical results in 60–90% of diseases, including angina pectoris, bronchial asthma, herpes simplex, and duodenal ulcers.
The following are some of the issues pointing to a fundamental problem:
- Ever since Beecher's 1955 study appeared, it has been claimed that about one third of the therapeutic effect observed in a typical trial is attributable to the placebo effect. But this is not what Beecher showed at all. In the "meta-analytic" section of his paper he gave the proportion of subjects across 15 trials deemed to have "been satisfactorily relieved by placebo" as 35.2% +/- 2.2%. This, if anything, is an estimate of the frequency of 'placebo-responders' in the aggregate trial group, but says nothing about the magnitude of the effect.
- Beecher, intentionally or otherwise, gave currency to the idea that the placebo effects were roughly constant at around 35%, and that the term could be usefully applied to all those variables otherwise called "non-specific" contributors to therapeutic outcomes - the natural (and unknowable) course of diseases, regression to the mean, expectation effects, changes in effect and other unquantifiable psycho-somatic features of illness, beliefs and therapeutic communication, etc. If anything is clear from subsequent studies, it is that the placebo effect is not constant, but strikingly variable. Placebo response rates all the way from zero to 100% have been reported in virtually every clinical condition studied (the variation in Beecher's own series was 15–58%). The so-called effect appears to be both universal and utterly unpredictable.
- Beecher, who was concerned to promote the use of Randomised controlled trials (RCTs) in clinical research, made an unjustified assumption which is almost certainly false - that placebo effects in the intervention and control arms of a trial will be identical, or nearly so, and independent of the therapeutic effects. In the rationalization of RCTs which followed, this claim has never been rigorously defended, and in specific instances, can be easily refuted.
- The original 1955 article of Beecher "The Powerful Placebo" claimed a 35% placebo effect in 15 studies. The original article was in 1997 re-analysed and "no evidence was found of any placebo effect in any of the studies" used by Beecher. The claimed "effects" were produced by spontaneous improvement, fluctuation of symptoms, regression to the mean, additional treatment, conditional switching of placebo treatment, scaling bias, irrelevant response variables, answers of politeness, experimental subordination, conditioned answers, neurotic or psychotic misjudgment, psychosomatic phenomena, misquotation, etc.
- Kaptchuk has shown that both the name and the concept of placebo were transferred from at least 200 years of use in clinical practice, in the decade following the second world war, to a new role required by the methodology of what was then the new discipline of 'clinical research'. Earlier usage corresponded to its Latin etymology - a harmless pill or potion given knowingly to patients who were either hard to please or hard to cure. The first clear example cited in the OED is from 1811. But during the post-war therapeutic revolution, it became the trashcan into which all the confounding factors that disturb therapeutic assessments were tipped. In Beecher's terms, it became a powerful if enigmatic distraction to researchers, whose results would be contaminated without rigorous procedures for its exclusion. Its modern use is therefore quite recent, and closely related to the adoption of the RCT as the methodological gold standard for trials of therapy.
- A considerable body of work has attempted to elucidate the 'mechanism' of the placebo effect - but without much success. Proposals ranging from 'suggestibility' and various other psychological hypotheses, to neuro-endocrine studies, and attribution of the effect to statistical artefacts, have turned out to be flawed in various ways, so that clinical researchers have no more idea of what is really going on in the control arms of their trials than did Hippocrates. It seems unlikely that this deeply unsatisfactory situation will be resolved by a new attempt to answer the old question; instead, as has been suggested by some of the most thoughtful students, we should expect to find that some part of the conceptual landscape in which this problematic entity resides must be reconstructed before it will come into focus. This view commends itself specially to those scholars who bring to the problem a perspective from outside the clinic - from medical anthropology, history of medicine, philosophy, and statistics.
# Inertness
Although placebos are generally characterized as pharmacologically inert substances or formulations, sham treatments, or inactive procedures, they are only inert, sham, ineffective, or inactive in the particular sense that they have no known cause and effect relationship with any of the pre-designated, biochemical, physiological, behavioural, emotional and/or cognitive outcomes of the pharmacologically active and known-to-be-efficacious intervention that might have otherwise been applied (see below).
Placebos are inactive or ineffective treatments or formulations; however a patient may experience either a positive or negative clinical effect while taking one. When a placebo is administered to mimic a previously administered drug, it may also incur the same side effects as the prior authentic drug. Most of these effects are thought to be psychological in nature or due to other unrelated factors. Not all placebos are equally effective. A placebo that involves ingestion, injection, or incision is often more powerful than a non-invasive technique. Placebos administered by authority figures such as general practitioners and other experts may also be more powerful than when this psychological authority effect is absent.
They are, however, not inert, sham, or inactive in any other manner of speaking; and they may well, in and of themselves, generate considerable change within any given subject, at any given time, under any given circumstances. According to Shapiro:
Actually the question of inert versus active placebo is academic, because there is no such thing as an inactive substance. For example, distilled water injections can cause hemolysis and water intoxication. Ingestion of two 5-grain capsules of sacchari lactis , QID , for 30 years, can result in a weight gain of 30 pounds, so that even sugar can hardly be considered harmless, indifferent, or inert.
# Nocebo
In the opposite effect, a patient who disbelieves in a treatment may experience a worsening of symptoms. This effect, now called by analogy the "nocebo effect" (Latin nocebo = "I will harm") can be measured in the same way as the placebo effect, e.g., when members of a control group receiving an inert substance report a worsening of symptoms. The recipients of the inert substance may nullify the placebo effect intended by simply having a negative attitude towards the effectiveness of the substance prescribed, which often leads to a nocebo effect, which is not caused by the substance, but due to other factors, such as the patient's mentality towards his or her ability to get well, or even purely coincidental worsening of symptoms.
# Etymology
The word placebo is Latin for "I will please". It is in Latin text in the Bible (Psalm 114:1–9, Vulgate version), from where it became familiar to the public via the Office of the Dead church service. From that, a singer of Placebo (at funeral) became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer.
Whenever a placebo is requested in a medical prescription it may imply a statement by the prescribing doctor that "This patient has come to me pleading for a treatment which does not exist or which I cannot or will not supply; I will please him by giving him something ineffectual and claiming that it is effectual." It could also indicate a belief that the effect was due to a subconscious desire of the patient to please the doctor. Since the placebo effect is in the patient not the doctor this may be more self-consistent. Early usage of the term does not indicate why it was chosen.
## Obecalp
Sometimes a doctor who does this, says that the fake medicine is "Obecalp", which is "placebo" spelt backwards. (and many other links)
# Early use
Originally, a placebo was a substance that a well-meaning doctor would give to a patient, telling him that it was a powerful drug (e.g., a painkiller), when in fact it was nothing more than a sugar pill. Thus, Hooper's medical dictionary of 1811 says placebo is "an epithet given to any medicine adapted more to please than benefit the patient." The subsequent reduction of the patient's symptoms was attributed to the patient's faith in his doctor and hence his belief in the drug. (This category, particularly before the first Medicines Act was passed, may merge into fake medicines.)
# Modern clinical application
Experimenters typically use placebos in the context of a clinical trial, in which a "test group" of patients receives the therapy being tested, and a "control group" receives the placebo. It can then be determined if results from the "test" group exceed those due to the placebo effect. If they do, the therapy or pill given to the "test group" is assumed to have had an effect.
# Origin of term "placebo effect"
Perhaps Graves (1920) was the first to speak of the placebo effect, when he spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced".
In 1933 (Evans and Hoyle) (using 90 subjects) and in 1937 (Gold, Kwit and Otto) (using 700 subjects) each published a study which compared the outcomes from the administration of an active drug and a dummy simulator (which both research groups called a placebo) in the same trial. Neither experiment displayed any significant difference between drug treatment and placebo treatment; leading the researchers to conclude that the drug exerted no specific effects in relation to the conditions being treated.
In 1946, the Yale biostatistician and physiologist E. Morton Jellinek was the first to speak of either a "placebo reaction" or a "placebo response". He speaks of a "response to placebo" (p.88), those who "responded to placebo" (p.88), a "reaction to placebo" (p.89), and of "reactors to placebo" (p.90). From this, it is obvious that, to Jellinek, the terms "placebo response" and "placebo reaction"—or the terms "placebo responder" and "placebo reactor"—were identical and interchangeable.
The general literature commonly misattributes the term "placebo effect" to Henry K. Beecher's 1955 paper The Powerful Placebo, where, however, he only speaks of placebo effects when he is contrasting them with drug effects; otherwise, he always speaks of "placebo reactors" and "placebo non-reactors".
Beecher (1952), Beecher, Keats, Mosteller, and Lasagna (1953), Beecher (1959), consistently speak of "placebo reactors" and "placebo non-reactors"; they never speak of any "placebo effect". Beecher (1970) simply speaks of "placebos".
# Isolation of cause
According to Kleijnen and his colleagues, healing is an interactive process between three influences:
- (1) the self-healing properties of the subject.
- (2) the non-specific effects induced by the presence of the therapist and the therapeutic setting.
- (3) the specific effects of the physical or pharmacological therapeutic interventions.
These effects are not isolated mutually-exclusive effects and, rather than just adding, they may help or hinder each other to various degrees. Also, Hyland (2003, p.348) notes that, in cases where “contextual factors contribute to a strong placebo response”, due to “the potentiating or adjunctive effect of the placebo response”, placebos can be used “potentiate the effect of an active treatment” that would have otherwise been far less efficacious.
From this notion that a “drug” has a specific treatment effect (i.e., the effect for which it has been administered), Perlman (2001, p.283) draws attention to three other treatment effects:
- non-specific effects: these are the side effects (“which are usually considered deleterious”);
- unintended effects: these are the placebo effects (“which… are still considered to be for the most part uncontrolled and unscientific”); and
- serendipitous effects: these are the “serendipitous effects of being in therapy, such as organizing effects of the therapeutic structure, inadvertent role modelling, outside knowledge of the therapist, chance remarks or encounters, and the influence of auxiliary personnel”.
In pursuit of establishing causation, the question “Who does what, with which, and to whom?” is central to task of identifying what are:
- specific effects (those for which the treatment was administered),
- non-specific effects (predictable "side effects"),
- unintended effects (i.e., the placebo responses),
- serendipitous effects of treatment (i.e., effects of the subject just being "in therapy"); Perlman (2001)(p.283) in discussing this suggests these as examples:
the "organizing effects of the therapeutic structure",
"inadvertent role modeling",
"outside knowledge of the therapist",
"chance remarks or encounters",
"the influence of auxiliary personnel" ("this category includes doormen, receptionists, cashiers, secretaries, security guards, janitors, and child care attendants", p.287).
- the "organizing effects of the therapeutic structure",
- "inadvertent role modeling",
- "outside knowledge of the therapist",
- "chance remarks or encounters",
- "the influence of auxiliary personnel" ("this category includes doormen, receptionists, cashiers, secretaries, security guards, janitors, and child care attendants", p.287).
Gaddum (1954) also recognizes that "changes in the incidence or severity of diseases in a hospital may be due to changes in the diet or changes in the nurses, which happen to coincide with the introduction of a new treatment" (pp.195–196).
In experiments with the common cold by Gold, Kwit & Otto (1937), in accounting for why those who received the placebo drug often experienced considerable benefit, Gold and his colleagues supposed that other, non-drug-related factors may have made a significant contribution to the apparent efficacy of the supposedly active drug, such as:
- Spontaneous variations in the course of the pain.
- Change in the weather.
- Change of occupation or amount of work.
- Change of diet.
- Change in eating habits with increase in the amount of rest before and after meals.
- Condition of the bowels.
- Emotional stress.
- Change in domestic affairs.
- Confidence aroused in the treatment.
- Encouragement afforded by any new procedure.
- A change of the medical adviser.
Also, due to the difficulty in ascribing causation, many phenomena overlap with, and are thus misattributed to, subjects' placebo responses (the phenomena are known as "confounders" or "lurking variables", such as:
- Natural termination of the disease process.
- Regression to the mean.
- Cyclical presentation of the disease.
- Errant diagnosis or prognosis.
- Temporary improvement confused with cure.
The placebo effect may be partly determined by genetics.
Open-label placebo vs double-blind placebo.
## Physician-patient relationship
Atributes of the physician, patient, and their relationship are important.
# Technical challenges and pitfalls
## Preventing subjects from recognizing a placebo
Appropriate use of a placebo in a clinical trial often requires or at least benefits from a double-blind study design, which means that neither the experimenters nor the subjects know which subjects are in the "test group" and which are in the "control group".
## Adherence to use of a placebo
The Coronary Drug Project was intended to study the safety and effectiveness of drugs for long-term treatment of coronary heart disease in men. Those in the placebo group who adhered to the placebo treatment (took the placebo regularly as instructed) showed nearly half the mortality rate as those who were not adherent.
A similar study of women similarly found survival was nearly 2.5 times greater for those who adhered to their placebo. This apparent placebo effect may be caused by:
- The psychological effect of adhering to the protocol, i.e. genuine placebo effect.
- Being healthy enough to follow the protocol.
- Compliant people being more diligent and scrupulous in all aspects of their lives.
## Need for psychoactive placebo
Because a belief that one has received the active drug can produce a markedly heightened placebo effect, it is often necessary to use a psychoactive placebo in clinical trials; i.e., a drug that produces enough physical effects to encourage the belief in the control and experimental groups that they have received the active drug.
A psychoactive placebo was used in the Marsh Chapel Experiment: a double-blind study, in which the experimental group received psilocybin while the control group received a large dose of niacin, a substance that produces noticeable physical effects.
Walter Pahnke in 1962 described his Marsh Chapel Experiment in his unpublished Ph.D. dissertation "Drugs and Mysticism: An Analysis of the Relationship between Psychedelic Drugs and the Mystical Consciousness, and submitted it in 1963, for his Ph.D. in Religion and Society at Harvard University; Timothy Leary was the principal academic advisor for his dissertation. In it, Pahnke wrote of administering capsules that contained 30mg of psilocybin extracted from psychoactive mushrooms, and contrasting their effects with those of psychoactive placebos, which contained the chemical niacin in such a dosage that it produced very significant physiological responses. It was intended that these responses would lead the control subjects to believe they had received the psychoactive drug.
The term "psychoactive placebo" is rare in the literature; but, when it is used, it always denotes a placebo of this type. For example, "Neither the experienced investigator nor the naive is easily fooled on the matter of whether he has received a psychedelic substance or merely a psychoactive placebo such as amphetamine." (Harman, McKim, Mogar, Fadiman & Stolaroff, 1966, p.215)
# Use in clinical trials
Placebo simulators are a standard control component of most clinical trials which attempt to make some sort of quantitative assessment of the efficacy of new medicinal drugs; It is a view held by many "that placebo-controlled studies often are designed in such a way that disadvantages the placebo condition" and, generally speaking, for a drug to be put on the market, it must be significantly more effective than its placebo counterpart.
According to Yoshioka (1998), the first-ever randomized clinical trial was the trial conducted by the Medical Research Council (1948) into the efficacy of streptomycin in the treatment of pulmonary tuberculosis.There were two test groups in this trial
- those "treated by streptomycin and bed-rest", and
- those " by bed-rest alone" (the control group).
What made this trial exceptional was that the subjects were randomly allocated to their test groups. The up-to-that-time practice was to allocate subjects alternately to each group, based on the order in which they presented for treatment. This practice was considered to be extremely biased, because those admitting each patient knew to which group that patient would be allocated (and it was considered that the decision to admit or not admit a specific patient might be influenced by the experimenter's knowledge of the nature of their illness, and their knowledge of the group to which the alternate allocation demanded they would occupy).
In recent times, the practice of using an additional natural history group as the trial's so-called "third arm" has emerged; and trials are conducted using three randomly-selected equally-matched trial groups, David (1949, p.28) wrote: "... it is necessary to remember the adjective ‘random’ should apply to the method of drawing the sample and not to the sample itself.".
- The Active drug group (A): who receive the active test drug.
- The Placebo drug group (P): who receive a placebo drug that simulates the active drug.
- The Natural history group (NH): who receive no treatment of any kind (and whose condition, therefore, is allowed to run its natural course).
The outcomes within each group are observed, and compared with each other, allowing us to measure:
- The efficacy of the active drug's treatment: the difference between A and NH (i.e., A-NH).
- The efficacy of the entire treatment process alone: the difference between P and NH (i.e., P-NH).
- The efficacy of the active drug's active ingredient: the difference between A and P (i.e., A-P).
- The magnitude of the placebo response: the difference between P and NH (i.e., P-NH).
Note that, depending upon the focus of your interest, the value of P-NH can either indicate the efficacy of the entire treatment process or the magnitude of the "placebo response".
The results of these comparisons then determine whether or not a particular drug is considered efficacious.
In recent times, as the demands for the scientific validation of the various claims that are made for the efficacy of various so-called "talking therapies" (such as hypnotherapy, psychotherapy, counselling, and non-drug psychiatry) has significantly increased, there is continuing controversy over what might or might not be an appropriate placebo for such therapeutic treatments.
In 2005, the Journal of Clinical Psychology, an eminent peer-reviewed journal (founded in 1945), devoted an entire issue to the question of "The Placebo Concept in Psychotherapy", and contained a wide range of articles that made many valuable contributions to this overall discussion.
# Placebo response as an index
In certain clinical trials of particular drugs, it may happen that the level of the "placebo responses" manifested by the trial's subjects are either considerably higher or lower (in relation to the "active" drug's effects) than one would expect from other trials of similar drugs. In these cases, with all other things being equal, it is entirely reasonable to conclude that:
- the degree to which there is a considerably higher level of "placebo response" than one would expect is an index of the degree to which the drug's active ingredient is not efficacious.
- the degree to which there is a considerably lower level of "placebo response" than one would expect is an index of the degree to which, in some particular way, the placebo is not simulating the active drug in an appropriate way.
However, in particular cases such as the use of Cimetidine to treat ulcers (see below), a significant level of placebo response can also prove to be an index of how much the treatment has been directed at a wrong target.
# Trials
"Heroic medicine" had begun to fall from favour long before research scientists such as Robert Koch, Louis Pasteur, Frederick Hopkins and Casimir Funk demonstrated that the presence or the absence of specific agents could cause specific diseases, and long before the chemical laboratory orientation of Abraham Flexner’s 1910 Flexner Report had evolved into the evidence-based medicine of the 1970s. As the earliest precursors of modern, scientific, conventional medicine began to emerge, medical scholars began to routinely question:
- the principles of their medical diagnosis and prognosis,
- the efficacy of their conventional medical practices,
- the correctness of their current anatomical, physiological and neurological knowledge, and
- the true scientific status of the drugs and therapies in their pharmacopoeia.
In many cases, active agents were identified in supposedly efficacious treatments; but it was found that some treatments had no efficacy whatsoever; and, regardless of how much they were accepted in the medical profession, or what they were supposed to do, they were medically useless.
Many, such as Pepper (1945, p.410) would strongly argue that, before the Countess of Chinchón learned of the medicinal properties of cinchona bark (perhaps the first time a real active ingredient had been isolated and identified), "there was basis for terming anything a placebo".
The aim of a clinical trial is to determine what treatments, delivered in what circumstances, to which patients, in what conditions, are the most efficacious; as well to obtain objective evidence of what treatments are efficacious and also specific, or are intentionally efficacious and also specific.
Gaddum (1953, p.195) wrote: "The first object of a therapeutic trial is to discover whether the patients who receive the treatment under investigation are cured more rapidly, more completely or more frequently, than they would have been without it."
## 1747: remedies for scurvy
In 1747, James Lind (1716–1794), the Naval Surgeon on HMAS Salisbury, conducted what was most likely the first-ever clinical trial when he investigated the efficacy of citrus fruit in cases of scurvy.
He randomly divided twelve scurvy patients, whose "cases were as similar as I could have them", into six pairs. Each pair was given a different remedy. Lind’s approach can still be seen in the way that the comparative efficacy of various treatments for particular sorts of cancer are determined, by examining and comparing the five year survival rates of those who have been treated with each of the different interventions. He noted that the pair who had been given the oranges and lemons were so restored to health within six days of treatment that one of them returned to duty, and the other was well enough to attend the rest of the sick.
According to Lind’s 1753 Treatise on the Scurvy in Three Parts Containing an Inquiry into the Nature, Causes, and Cure of the Disease, Together with a Critical and Chronological View of what has been Published of the Subject, the remedies were:
- one quart of cider per day,
- twenty-five drops of elixir vitriol (sulfuric acid) three times a day,
- two spoonfuls of vinegar three times a day,
- a course of sea-water (half a pint every day),
- two oranges and one lemon each day,
- an electuary (Dunn, 1997, p.F65).
Gaddum (1954, p.196) wrote that the electuary had been recommended to Lind by a hospital surgeon, and that it contained garlic, mustard, balsam of Peru, and myrrh.
## 1784: animal magnetism
In 1784, the French Royal Commission looked into the existence of animal magnetism and investigated the practices of Charles d’Eslon (1739–1786), comparing the effects of his allegedly "magnetized" water with that of plain water.
It did not examine the practices of Franz Mesmer, but examined the significantly different practices of his associate Charles d’Eslon.
See animal magnetism for more information.
## 1799: Perkins tractors
In 1799, John Haygarth investigated the efficacy of medical instruments called "Perkins tractors", by comparing the results from dummy wooden tractors with a set of allegedly "active" metal tractors.
## 1863: placebo compared with active treatment
In 1863 Austin Flint (1812–1886) conducted the first-ever trial that directly compared the efficacy of a dummy simulator with that of an active treatment; although Flint's examination did not compare the two against each other in the same trial. Even so, this was a significant departure from the (then) customary practice of contrasting the consequences of an active treatment with what Flint described as "the natural history of disease".
Flint’s paper is the first time that either of the terms "placebo" or "placeboic remedy" were ever used to refer to a dummy simulator in a clinical trial.
... to secure the moral effect of a remedy given specially for the disease, the patients were placed on the use of a placebo which consisted, in nearly all of the cases, of the tincture of quassia, very largely diluted. This was given regularly, and became well known in my wards as the placeboic remedy for rheumatism.
Flint (1863, p.21) treated 13 hospital inmates who had rheumatic fever; 11 were "acute", and 2 were "sub-acute". He then compared the results of his dummy "placeboic remedy" with that of the active treatment’s already well-understood results. (Flint had previously tested, and reported on, the active treatment’s efficacy.) There was no significant difference between the results of the active treatment and his "placeboic remedy" in 12 of the cases in terms of disease duration, duration of convalescence, number of joints affected, and emergence of complications (pp.32–34). In the thirteenth case, Flint expressed some doubt as to whether the particular complications that had emerged (namely, pericarditis, endocarditis, and pneumonia) would have been prevented if that subject had been immediately given the "active treatment" (p.36).
## 1946: a headache remedy ingredient
In post-World War II 1946, pharmaceutical chemicals were in short supply. One U.S. headache remedy manufacturer sold a drug that was composed of three ingredients: a, b, and c. Chemical b was in short supply.
Jellinek was asked to test whether or not the headache drug's overall efficacy would be reduced if ingredient b was missing.
Jellinek set up a complex trial involving 199 subjects, all of whom suffered from "frequent headaches". (Originally there were 200 subjects, but one did not complete the trial.) The subjects were randomly divided into four test groups. He prepared four test drugs, involving various permutations of the three drug constituents, with a placebo as a scientific control. The structure of this trial is significant because, in those days, the only time placebos were ever used "was to express the efficacy or non-efficacy of a drug in terms of "how much better" the drug was than the "placebo". (Jellinek (1946), p.88. Note that the trial conducted by Austin Flint is an example of such a drug efficacy vs. placebo efficacy trial.) The four test drugs were identical in shape, size, colour and taste:
- Drug A: contained a, b, and c.
- Drug B: contained a and c.
- Drug C: contained a and b.
- Drug D: a 'simulator', contained "ordinary lactate".
Each time a subject had a headache, they took their group’s designated test drug, and recorded whether their headache had been relieved (or not). Although "some subjects had only three headaches in the course of a two-week period while others had up to ten attacks in the same period", the data showed a "great consistency" across all subjects (Jellinek, 1946, p.88). Every two weeks the groups’ drugs were changed; so that by the end of eight weeks, all groups had tested all the drugs.
The stipulated drug (i.e., A, B, C, or D) was taken as often as necessary over each two-week period, and the two week sequences were:
- A, B, C, D
- B, A, D, C
- C, D, A, B
- D, C, B, A.
Each group took a test remedy for two weeks. The trial lasted eight weeks, and by the end of the trial all groups had taken each test drug for two weeks (although each group had taken them in a different sequence). Over the entire population of 199 subjects, 120 of the subjects responded to the placebo, and 79 did not; i.e., there were 120 "subjects reacting to placebo" and 79 "subjects not reacting to placebo".
At first glance there was no difference between the self-reported "success rates" of Drugs A, B, and C (84%, 80%, and 80% respectively) (the "success rate" of the simulating placebo Drug D was 52%); and, from this, it appeared that ingredient b was completely unnecessary.
However, in quite a remarkable way, the trial eventually did demonstrate that ingredient b did make a significant contribution to the remedy’s efficacy. Examining his data more closely, Jellinek discovered that there was a very significant difference in responses between the 120 placebo-responders and the 79 non-responders. The 79 non-responders' reports showed that if they were considered as an entirely separate group, there was a significant difference the "success rates" of Drugs A, B, and C: viz., 88%, 67%, and 77%, respectively. And because this significant difference in relief from the test drugs could only be attributed to the presence or absence of ingredient b, he concluded that ingredient b was essential (thus contradicting his initial conclusion, derived from the comparison between the "success rates" for all test subjects, that Drugs A, B, and C were equally efficacious).
There were two further repercussions from this trial:
- Jellinek (p.90), having identified 120 "placebo reactors", went on to suppose that all of them may have been suffering from either "psychological headaches" (with or without attendant "hypochondriasis" (p.90)) or "true physiological headaches accessible to suggestion". Thus, according to this view, the degree to which a "placebo response" is present tends to be an index of the psychogenic origins of the condition in question.
- It indicated that, whilst any given placebo was inert, a responder to that particular placebo may be responding for a wide number of reasons unconnected with the drug's active ingredients; and, from this, it could be important to pre-screen potential test populations, and treat those manifesting a placebo-response as a special group, or remove them altogether from the test population.
## 1983: cimetidine
This test wrongly seemed to show that cimetidine was a placebo, because they did not know that the bacterium Helicobacter pylori was sometimes present and interfering with results.
In 1983 medical anthropologist Daniel Moerman conducted a meta-study of 31 placebo-controlled trials of the gastric acid secretion inhibitor drug Cimetidine in the treatment of gastric or duodenal ulcers. His meta-study revealed that the placebo treatments were, in many cases, just as effective in treating ulcers as the active drug: of the 1692 patients treated in the 31 trials, 76% of the 916 treated with the drug were "healed", and 48% of the 776 treated with placebo were "healed". These results were confirmed by the direct post-treatment endoscopy of the treated area. He also found that German placebos were "stronger" than others; and that, overall, different physicians evoked quite different placebo responses in the same clinical trial (p.15).
Further examination revealed that many of these trials had been conducted in such a way that the gap between the active drugs and the placebo controls was "not because had high drug effectiveness, but because they had low placebo effectiveness" (p.13).
In some trials, placebos were effective in 90% of the cases, whilst in others the placebos were only effective in 10% of the cases. Moerman argues that "what is demonstrated in studies is not enhanced healing in drug groups, but reduced healing in placebo groups" (p.14).
Moerman also noted the results of two studies (one conducted in Germany, the other in Denmark), which examined "ulcer relapse in healed patients". Each study showed that the rate of relapse amongst those "healed" by the active drug treatment was five times that of those "healed" by the placebo treatment (pp.14–15). This led Moerman to remark: “we may be able to go so far as to say that while “heals” ulcers, placebo treatment can “cure” ulcer disease” (p.14).
These results of a 90% placebo response rate, and a placebo-healed relapse rate 20% that of the active drug seems to indicate that the drug Cimetidine was not effective in inhibiting gastric acid secretion.
However, as we now know, the majority of gastric or duodenal ulcers are not due to excessive gastric acid secretion caused by stress or spicy food, but are due to the bacterium Helicobacter pylori, it is highly significant that this high response rate and low relapse rate can now be interpreted otherwise: it was indicating that the drug's prescribers had chosen the wrong target for their therapeutic intervention (and, as a consequence, we now know that they had chosen what might be termed an "inappropriate target but correct drug", rather than a "correct target but inappropriate drug" as was first supposed).
## Placebo-controlled studies
Beecher (1955) reported that about a quarter of patients who were administered a placebo, for example against back pain, reported a relief or diminution of pain. Remarkably, not only did the patients report improvement, but the improvements themselves were often objectively measurable, and the same improvements were typically not observed in patients who did not receive the placebo.
Because of this effect, government regulatory agencies approve new drugs only after tests establish not only that patients respond to them, but also that their effect is greater than that of a placebo (by way of affecting more patients, by affecting responders more strongly or both). Such a test or clinical trial is called a placebo-controlled study.
Because a doctor's belief in the value of a treatment can affect his or her behaviour, and thus what his or her patient believes, such trials are usually conducted in "double-blind" fashion: that is, not only are the patients made unaware when they are receiving a placebo, the doctors are made unaware too. Recently, it has even been shown that "mock" surgery can have similar effects, and so some surgical techniques must be studied with placebo controls (rarely double blind, due to the difficulty involved). To merit approval, the group receiving the experimental treatment must experience a greater benefit than the placebo group.
Nearly all studies conducted this way show some benefit in the placebo group. For example, Khan published a meta-analysis of studies of investigational antidepressants and found a 30% reduction in suicide and attempted suicide in the placebo groups and a 40% reduction in the treated groups. (Khan 2000) However, studies generally do not include an untreated group, so determining the actual size of the placebo effect, compared to totally untreated patients, is difficult.
# Effect on various symptoms
## Pain
Placebo may bae able to reduce pain according to a systematic review by the Cochrane Collaboration. More recent studies confirm this and suggest that placebos that are perceived to be more expensive are more effective.
The effect is more pronounced with pre-existing pain than with experimentally induced pain. People can be conditioned to expect analgesia in certain situations. When those conditions are provided to the patient, the brain responds by generating a pattern of neural activity that produces objectively quantifiable analgesia. (Benedetti 2003, Wager 2004)
Evans argued that the placebo effect works through a suppression of the acute phase response, and as a result does not work in medical conditions that do not feature this. (Evans 2005) The acute phase response consists of inflammation and sickness behaviour:
- Four classic signs of ‘inflammation’: tumor, rubor, calor, and dolor – (Latin for "swelling, redness, heat, and pain").
- Sickness behaviour: lethargy, apathy, loss of appetite, and increased sensitivity to pain.
## Depression
A brain-imaging study found that depressed patients who responded to the placebo effect showed changes in cerebral blood flow, which were similar to the changes in brain function seen in patients who responded to anti-depressant medication. (Leuchter 2002) Other studies argue that up to 75% of the effectiveness of anti-depressant medication is due to the placebo-effect rather than the treatment itself. (Khan 2000)
## Withdrawal symptoms on discontinuation
The Women's Health Initiative study of hormone replacement therapy for menopause was discontinued after participants still in the program had been taking either hormones or placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 40.5% of those on placebo compared to 63.3% of those on hormone replacement. Pain and stiffness (musculoskeletal symptoms) were the most frequently reported symptoms in both the placebo group (22.2%) and the hormone group (36.8%), exceeding other symptoms by more than 10%. Of those reporting pain and stiffness, 54.7% in the hormone group and 38.3% in the placebo group had these symptoms at the onset of therapy. Tiredness
was the second most frequently reported withdrawal symptom (21.3% hormone, 11.6% placebo) and hot flashes/night sweats the third (21.2% hormone, 4.8% placebo). Only the vasomotor symptoms (hot flashes/night sweats) were acknowledged to be verified effects of menopause by a 2005 National Institutes of Health panel.
These results may indicate some learned response concerning which withdrawal symptoms appear in a placebo group as well as in the subjects who received therapy, with a greater effect on pain and tiredness than on vasomotor symptoms.
## Objective and subjective effects
Hrobjartsson and Götzsche published a study in 2001 and a follow-up study in 2004 questioning the nature of the placebo effect. (Hrobjartsson 2001, Hrobjartsson 2004) They performed two meta-analyses involving 156 clinical trials in which an experimental drug or treatment protocol was compared to a placebo group and an untreated group, and specifically asked whether the placebo group improved compared to the untreated group. Hrobjartsson and Götzsche found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group. Similarly, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could only be documented in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have "powerful clinical effects," (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from bias.
These results suggest that the placebo effect is largely subjective. This would help explain why the placebo effect is easiest to demonstrate in conditions where subjective factors are very prominent or significant parts of the problem. Some of these conditions are headache, stomachache, asthma, allergy, tension, and the experience of pain, which is often a significant part of many mild and serious illnesses.
# Mechanism for the effect
It is universally accepted that, for a placebo response to occur, the subject must believe an effective medication (or other treatment) has been administered to them, but must not know it is an ineffective placebo. This is quite different from the case of an "active drug", where the drug response is generated even in the case of covert administration, in other words regardless of whether the patient knows or doesn't know they have received any medication.
The question of just how and why placebo responses are generated is not an abstract theoretical issue; it has wide implications for both clinical practice and the experimental evaluation of therapeutic interventions.
In recent times, three different hypotheses have been offered to account for these placebo responses — i.e., "expectancy theory" and 'classical conditioning" and motivation — which, whilst emphasizing different factors, are not mutually exclusive and, in fact, overlap to a certain extent.
## Expectancy effect
The subject-expectancy effect attributes the placebo effect to conscious or unconscious manipulation by patients in reporting improvement. Hrobjartsson and Götzsche argued in their article, "Most patients are polite and prone to please the investigators by reporting improvement, even when no improvement was felt." Subjective bias can also be unconscious, where the patient believes he is improving as a result of the attention and care he has received.
## Conditioning
Classical conditioning is a type of associative learning where the subject learns to associate a particular stimulus with a particular response. In this case the stimulant is the substance perceived as medicine but is the placebo, and the response is the relief of symptoms. It is difficult to tell the difference between conditioning and the expectancy effect when the outcome is subjective and reported by the patient. However, conditioning can result in measurable biological changes similar to the changes seen with the real treatment or drug. For example, studies showing that placebo treatments result in changes in brain function similar to the real drug are probably examples of conditioning resulting in objectively measurable results. (Sauro 2005, Wager 2004, Arnaldo 2002)
## Motivation
Motivational explanations of the placebo effect have typically considered the placebo effect to be an outcome of one’s desire to feel better, reduce anxiety, or cooperate with an experimenter or health care professional (Price et al. 1999, Margo 1999). The motivational perspective is supported by recent research showing that nonconscious goals for cooperation can be satisfied by confirming expectations about a treatment (Geers et al. 2005).
## Role of endogenous opiates
The discovery in 1975 of Endogenous opiates alias endorphins (substances like opiates but naturally produced in the body) have changed matters in investing placebo effect. When patients who claimed to experience pain relief after receiving a placebo were injected with naloxone (a drug that blocks the effects of opiates), their pain returned, suggesting that the placebo effect may be partly due to psychological reaction causing release of natural opiates. (Sauro 2005)
# Biological substrates of the placebo response
A "placebo response" can amplify, diminish, nullify, reverse or, even, divert the action of an "active" drug.
Because a "placebo response" is just as significant in the case of an "active" drug as it is in the case of an "inert" dummy drug, the more that we can discover about the mechanisms that produce "placebo responses", the more that we can enhance their effectiveness and convert their potential efficacy into actual relief, healing and cure.
Recent research strongly indicates that a "placebo response" is a complex psychobiological phenomenon, contingent upon the psychosocial context of the subject, that may be due to a wide range of neurobiological mechanisms (with the specific response mechanism differing from circumstance to circumstance).
The very existence of these "placebo responses" strongly suggest that "we must broaden our conception of the limits of endogenous human control"; and, in recent times, researchers in a number of different areas have demonstrated the presence of biological substrates, unique brain processes, and neurological correlates for the "placebo response":
- 2001: de la Fuente-Fernández and colleagues reported their PET scan findings on test subjects with Parkinson's disease.
- 2002: Petrovic and colleagues reported their PET scan findings on test subjects in a trial of opioid analgesia.
- 2002: Mayberg and colleagues reported their PET scan findings on test subjects with unipolar depression.
- 2004: Wager and colleagues reported their fMRI scan findings on test subjects in a trial of placebo analgesia.
- 2004: Lieberman and colleagues reported their PET scan findings on test subjects with Irritable bowel syndrome.
- 2006: Bingel and colleagues reported their fMRI scan findings on test subjects in a trial of placebo analgesia.
- 2006: Zubieta and colleagues reported their PET scan findings on test subjects in a trial of placebo analgesia.
- 2006: Sarinopoulos and colleagues reported their fMRI scan findings on test subjects in a trial neural responses to a highly aversive bitter taste.
A complex fMRI-centred study by McClure, et al. (2004) on the brain responses of subjects who had previously expressed a preference for one or other of the similar soft drinks Pepsi and Coca-Cola, demonstrated that "brand information", which "significantly influences subjects’ expressed preferences", is processed in an entirely different brain area from the area activated in blind taste tests (when their "preferences are determined solely from sensory information"). This supports the claim that there are unconscious brain processes that activate the "placebo response".
# Ethical challenges and concerns
Bioethicists have raised diverse concerns on the use of placebos in modern medicine and research. These have been largely incorporated into modern rules for the use of placebos in research but some issues remain subject to debate. The ethics of prescribing placebos in medical practice is highly debated. Some practitioners argue that the use of placebos is sometimes justified because it will do no harm and may do some good. With the publication of studies by Hróbjartsson and Götzsche and others, the proposition that placebos may do some good is under fire.
- Disclosure. Rules that govern modern clinical trials insist on full disclosure to subjects who take part. Today, subjects are told that they may receive the drug being tested or they may receive the placebo.
- Balancing Treatment vs. Research Objectives. Ethicists have also raised concerns on the use of placebos in those circumstances in which a standard treatment exists unless there are genuine doubts of the effectivity of such standard treatment. If standard treatments exist for the disease being studied in clinical trials, a standard treatment is always used in place of a placebo for serious diseases. In research experimental studies, the method of establishing a proper control group to eliminate the placebo effect has also been difficult, particularly for surgical and therapy interventions that are not pharmaceutical in nature. Notably, there has been much debate of whether to use a placebo pill or conduct a sham procedure as a control.
Most of these concerns have been addressed in the modern conventions for the use of placebos in research; however, some issues remain subject to debate.
From the time of the Hippocratic Oath questions of the ethics of medical practice have been widely discussed, and codes of practice have been gradually developed as a response to advances in scientific medicine.
The Nuremberg Code, which was issued in August 1947, as a consequence of the so-called Doctors' Trial which examined the human experimentation conducted by Nazi doctors during World War II, offers ten principles for legitimate medical research, including informed consent, absence of coercion, and beneficence towards experiment participants.
In 1964, the World Medical Association issued the Declaration of Helsinki, which specifically limited its directives to health research by physicians, and emphasized a number of additional conditions in circumstances where "medical research is combined with medical care".
The significant difference between the 1947 Nuremberg Code and the 1964 Declaration of Helsinki is that the first was a set of principles that was suggested to the medical profession by the "Doctors’ Trial" judges, whilst the second was imposed by the medical profession upon itself.
Paragraph 29 of the Declaration makes specific mention of placebos:
29. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.
In 2002, World Medical Association issued the following elaborative announcement:
Note of clarification on paragraph 29 of the WMA Declaration of HelsinkiThe WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:
All other provisions of the Declaration of Helsinki must be adhered to, especially the need for appropriate ethical and scientific review.
In addition to the requirement for informed consent from all drug-trial participants, it is also standard practice to inform all test subjects that they may receive the drug being tested or that they may receive the placebo.
A poll of 679 American internists and rheumatologists in the fall of 2008 revealed that approximately half of the physicians routinely prescribe placebos to their patients. Pain relievers and vitamins were the most frequently prescribed placebos, but many doctors also reported prescribing antibiotics and sedatives. The finding raised ethical concerns over informed consent and trust in the doctor-patient relationship as only 5 percent of the doctors revealed to their patients that the treatment was some form of placebo. Full results of the study were published in BMJ.
# Doctor-patient relationship
A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the past year. The most frequently prescribed placebos were antibiotics for viral infections, and vitamins for fatigue. Specialists and hospital-based physicians reported much lower rates of placebo use. (Hrobjartsson 2003) A 2004 study in the British Medical Journal of physicians in Israel found that 60% used placebos in their medical practice, most commonly to "fend off" requests for unjustified medications or to calm a patient. Of the physicians who reported using placebos, only 15% told their patients they were receiving placebos or non-specific medications. (Nitzan 2004) An accompanying editorial stated,
The placebo effect, thought of as the result of the inert pill, can be better understood as an effect of the relationship between doctor and patient. Adding the doctor's caring to medical care affects the patient's experience of treatment, reduces pain, and may affect outcome. This survey makes it clear that doctors continue to use placebos, and most think they help.
The editorial suggested there were problems with Hróbjartsson and Götzsche's methods and argued that their results show that placebos can't cure everything, but don't prove that the placebo effect cures nothing. The editorial concluded, "We cannot afford to dispense with any treatment that works, even if we are not certain how it does." (Spiegel 2004)
The editorial prompted responses on both sides of the issue.
- Critics of the practice responded that it is unethical to prescribe treatments that don't work, and that telling a patient that a placebo is a real medication is deceptive and harms the doctor-patient relationship in the long run. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions.
- Defenders of the use of placebos suggested that placebos do not work in clinical trials because the subjects know they might be getting a placebo, but do work in medical practice where the patient believes he or she is getting an active drug. Other writers pointed to the empirical data showing that placebos can have measurable biological effects, especially in pain relief (see above), or argued that the use of a placebo to "please the patient" fosters real healing as part of a caring doctor-patient relationship. (Barfod 2005, Di Blasi 2005)
BMJ posted a series of responses to Dr. Spiegel's editorial online in their rapid response section. Selected responses were published in later issues of the Journal.
In addition, there are the impracticalities of placebos:
- Roughly only 30% of the population seems susceptible to placebo effects, and it is not possible to determine ahead of time for whom a placebo will work and for whom it will not.
- All placebo effects eventually wear off, thus making the placebo effect impractical for long term or chronic medical matters.
- Patients rightfully want immediate relief or improvement from their illness or symptoms. A non-placebo can often provide that, while a placebo might not.
- Legitimate doctors and pharmicists could open themselves up to charges of fraud since sugar pills would cost pennies or cents for a bottle, but the price for a "real" medication would be have to be charged to avoid making the patient suspicious.
- Unscrupulous medical practitioners could swindle patients with fake surgeries and sugar pills, then later claim that they only meant to help their patients by using "placebos".
About 25% of physicians in both the Danish and Israeli studies used placebos as a diagnostic tool to determine if a patient's symptoms were real, or if the patient was malingering. Both the critics and defenders of the medical use of placebos agreed that this was unethical. The British Medical Journal editorial said, "That a patient gets pain relief from a placebo does not imply that the pain is not real or organic in origin...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."
The placebo administration may prove to be a useful treatment in some specific cases where recommended drugs can not be used. For example, burn patients who are experiencing respiratory problems cannot often be prescribed opioid (morphine) or opioid derivatives (pethidine), as these can cause further respiratory depression. In such cases placebo injections (normal saline, etc.) are of use in providing real pain relief to burn patients if they (those not in delirium) are told that are being given a powerful dose of painkiller.
There is general agreement that placebo control groups are an important tool for controlling for several types of possible bias, including the placebo effect, in double blind clinical trials.
The placebo effect is an active area of research and discussion and it is possible that a clear consensus regarding the use of placebos in medical practice will emerge in the future.
# Use as morale-boosters
Hooper’s (1811) Quincy’s Lexicon-Medicum defines placebo as "an epithet given to any medicine adapted more to please than benefit the patient".
In the practice of medicine it had been long understood that, as Ambroise Paré (1510–1590) had expressed it, the physician’s duty was to "cure occasionally, relieve often, console always" ("Guérir quelquefois, soulager souvent, consoler toujours").
According to Jewson, eighteenth century English medicine was gradually moving away from the patient having a considerable interaction with the physician—and, through this consultative relationship, having an equal influence on the construction of the physician’s therapeutic approach—and it was gradually moving towards that of the patient being the recipient of a far more standard form of intervention that was determined by the prevailing opinions of the medical profession of the day.
Jewson characterizes this as parallel to the changes that were taking place in the manner in which medical knowledge was being produced; namely, a transition all the way from "bedside medicine", through "hospital medicine", to "laboratory medicine".
For more on the effect of the development of various types of medical technology see Medical sign#Increased reliance on signs.
From this point of view, the last vestiges of the "consoling" approach to treatment are to be found in the administration—often without any sort of adequate history being taken, or any sort of appropriate physical examination being made -- of the morale-boosting and pleasing remedies, such as the "sugar pill", electuary or pharmaceutical syrup; all of which had no known pharmacodynamic action.
Those doctors who provided their patients with these sorts of morale-boosting therapies (which, whilst having no pharmacologically active ingredients, provided reassurance and comfort) did so either to reassure their patients whilst the vis medicatrix naturæ (i.e., "the healing power of nature") performed its normalizing task of restoring them to health, or to gratify their patients’ need for an active treatment.
Some statements about placebos in scientific articles are:
- Cooper (1823, p.259): " the compound decoction of the sarsaparilla ... irritable ulcer, ... some think it placebo; others have a very high opinion of its efficacy ... after the use of mercury, it diminishes the irritability of the constitution, and soon soothes the system into peace" (emphasis added).
- Shapiro (1968, p.656): " positioning ... Introduction of the word placebo to describe a class of treatments not previously specified was an important development in the history of methodology and medicine."
- Handfield-Jones (1953): "some patients are so unintelligent, neurotic, or inadequate as to be incurable, and life is made easier for them by placebo".
- Platt (1947, p.307): "the frequency with which placebos are used varies inversely with the combined intellligence of the doctor and his patient".
- Steele (1891, pp 277–278)"To argue with a man, and especially with a woman, that there is little the matter with them might be thought injudicious, and to advise them to return at a more convenient occasion requires more time and resolution than writing out a prescription or administering a placebo."
- But Shapiro (1968, p.679): "If a placebo is prescribed by a physician because it is thought that it will help the patient, then it is a specific and therefore not a placebo ."
- An editorial in the British Medical Journal of 19 January 1952 (p.150): "But it is a fallacy to suppose that an inactive medicine can do no harm. If prescribed in a perfunctory way for a patient needing explanation and reassurance it may increase faith in his disease rather than in the remedy, and a doctor who gives a placebo in the wrong spirit may harm the patient."
- Pepper (1945, p.411): "There may be a time when during the carrying out of diagnostic tests it is undesirable to give potent medicine lest it interfere with the tests and yet the patient must be encouraged by treatment. ... there is a certain amount of skill in the choice and administration of a placebo. In the first place, it must be nothing more than what the name implies a medicine without any pharmacologic action whatever. Even a mild sedative is not a true placebo. Secondly, its name must be unknown to even the most inveterate patient who knows most drugs by name and is always quick to read the prescription. If the medicines named are familiar, the type of patient who needs a placebo will promptly exclaim that this or that drug had been tried and "had not helped me" or "had upset my stomach". It is well if the drug have a Latin and polysyllabic name; it is wise if it be prescribed with some assurance and emphasis for psychotherapeutic effect. The older physicians each had his favorite placeboic prescriptions—one chose Tincture of Condurango, another the Fluidextract of Cimicifuga nigra. Certainly this latter by its Latin name might be expected to have more supratentorial action than if one merely wrote for the Black Cohosh, and Condurango would be more efficacious than sugar of milk." Pepper's assertion that a placebo "must be nothing more than what the name implies"—namely that it must be "a medicine without any pharmacologic action whatever"—in order for it to be called a placebo, is most significant.
- Findley (1953), p.1826 & p.1824: " used as an instrument of deception, but as a technique for cementing the emotional bond which must attach doctor to patient if any form of treatment is to be really successful… the most important weapon the physician has ... in proportion as this bond is firm, the need for drugs will likely diminish."
- Leslie (1954, p.854): "Because medicine has been so concerned with its scientific growth too little attention has been paid to advancing the art of medicine, to which therapy with placebos belongs, and consequently knowledge of the use of placebos has not progressed significantly."
- Carruthers, Hoffman, Melmon & Nierenberg (2000, p.1268): "In clinical practice, where a majority of patient visits are for conditions that cannot be explained on a pathophysiologic basis of for which no specific treatment is available, it is essential that physicians understand the concepts and principles of placebos and placebo effects and, when appropriate, use them correctly".
## "Placebo" as a pejorative
Useless decoctions, drugs, treatments, remedies, and procedures are given the pejorative label placebo.
In the 14th century the English word "placebo" denoted a sycophant and a useless flatterer, but this usage became obsolete.
The second edition of Motherby’s (1785) New Medical Dictionary defines "placebo" as "a common place method or medicine" (not "a common place method of medicine" as often misquoted.)
Because this usage does not appear in English (or in any English, French, German, Italian, or Portuguese dictionary) before Motherby’s 1785 edition, Shapiro (1968, pp.656–657) is certain that this pejorative use of placebo was coined by Motherby. That Samuel Johnson's 1755 Dictionary of the English Language has no entry for placebo (or for placebo-singer or singer of placebo, see Placebo (at funeral)), strongly supports Shapiro's contention.
# Examples of effect
In 1938, Diehl, Baker and Cowan reported the results of a study that they had conducted over a two year period into the efficacy of injected vaccines in prevention of colds. Whilst their experimental group showed a significant reduction in the number of colds per person per year, the placebo control group reported the same magnitude of reduction as the vaccinated group. This finding was significant, because they also found that their observed level of reduction in the number of colds per person per year matched that of other "uncontrolled studies"; which, given the demonstrated level of placebo responses, meant that "there is no evidence in this study… that vaccines reduce the complications of colds… in a cold-susceptiible group".
By 1948, the term placebo effect was so widely established that an Egyptian physician could write to The Lancet, reporting that "The success achieved in 83% of cases cannot by any means be ascribed to suggestion or to a placebo effect."
In 1949, Wolf conducted a series of investigations into the "measurable 'drug effects' that are not attributable to the chemical properties of the agents administered". Wolf contrasting what he called drug effects with what he called placebo effects.
He noted the extent to which the " "placebo" actions depended for their force on the conviction of the patient that this or that effect would result". He drew attention to the impressive frequency and magnitude of these placebo actions and placebo effects and how they could mimic, mask, potentiate, or prevent beneficial responses to the active drugs. He also stressed that all of these placebo actions and placebo effects, "which the pharmacologic action of drugs or inert agents with potency" were associated with real and substantial physiological changes; and, therefore, they were not imaginary. His study also revealed that the action of a drug could be nullified or, even, reversed in the presence of emotional states such as anger, hostility or resentment.
He also observed that "these effects at times more potent than the pharmacologic action customarily attributed to the agent". and spoke of the well-established understanding "that the mechanisms of the body are capable of reacting not only to direct physical and chemical stimulation but also to symbolic stimuli, words and events which have somehow acquired special meaning for the individual", in the hope that, "in the future drugs will be assessed not only with reference to their pharmacologic action but also to the other forces at play and to the circumstances surrounding their administration".
# Methodology of administration
Placebos are things like sugar pills, that look like real treatments but in fact have no physical effect. They are used to create "blind" trials in which the participants do not know whether they are getting the active treatment or not, so that physical effects can be measured independently of the participants' expectations. There are various effects of expectations, and blind trials control all of these together by making whatever expectations there are equal for all cases. Placebos are not the only possible technique for creating "blindness" (= unawareness of the treatment): to test the effectiveness of prayer by others, you just don't tell the participants who has and has not had prayers said for them. To test the effect of changing the frequency of fluorescent lights on headaches, you just change the light fittings at night in the absence of the office workers (this is a real case).
Related to this is the widespread opinion that placebo effects exist, where belief in the presence of a promising treatment (even though it is in fact an inert placebo) creates a real result e.g. recovery from disease. Placebos as a technique for "blinding" will remain important even if there is no placebo effect, but obviously it is in itself interesting to discover whether placebo effects exist, how common they are, and how large they are. After all, if they cure people then we probably want to employ them for that.
Claims that placebo effects are large and widespread go back to at least Beecher (1955). However Kienle and Kiene (1997) did a reanalysis of his reported work, and concluded his claims had no basis in his evidence. Beecher misinterpreted his data. Also, Beecher's methodology was very questionable. Then Hrobjartsson & Gotzsche (2001) did a meta-analysis or review of the evidence, and concluded that most of these claims have no basis in the clinical trials published to date. This opinion is widely spread in the placebo literature. The chief points of their skeptical argument are:
- Only trials that compare a group that gets no treatment with another group that gets a placebo can test the effect.
- Most claims are based on looking at the size of the improvement measured in placebo groups in trials comparing only placebo and experimental (active) treatments. This is misleading since (for instance) most diseases have a substantial clearup rate with no treatment: seeing improvements does not mean the placebo had an effect. (Put more technically, comparing with the baseline (pretest measure) is vulnerable to regression to the mean.)
Nevertheless, even they conclude that there is a real placebo effect for pain (not surprising since this is partly understood theoretically: Wall, 1999)); and for some other continuously-valued subjectively-assessed effects. A recent experimental demonstration was reported: Zubieta et al. (2005) "Endogenous Opiates and the Placebo Effect" The journal of neuroscience vol.25 no.34 p.7754–7762
This seems to show that the psychological cause (belief that the placebo treatment might be effective in reducing pain) causes opioid release in the brain, which then presumably operates in an analogous way to externally administered morphine.
A recent and more extensive review of the overall dispute is: M. Nimmo (2005) Placebo: Real, Imagined or Expected? A Critical Experimental Exploration Final year undergraduate Critical Review, Dept. of Psychology, University of Glasgow. PDF copy. | Placebo
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Placebo effect is the term applied by medical science to the therapeutic and healing effects of inert medicines and/or ritualistic or faith healing practices.[1][2] When referring to medicines, a placebo is a preparation which is pharmacologically inert but which may have a therapeutic effect based solely on the power of suggestion. It may be administered in any of the ways in which pharmaceutical products are administered.[3]
Sometimes known as non-specific effects or subject-expectancy effects, a placebo effect (or its counterpart, the nocebo effect), occurs when a patient's symptoms are altered in some way (i.e., alleviated or exacerbated) by an otherwise inert treatment, due to the individual expecting or believing that it will work.
The placebo effect occurs when a patient takes an inert substance (sometimes called a "sugar pill") in conjunction with the suggestion from an authority figure or from acquired information that the pill will aid in healing and the patient’s condition improves. This effect has been known since the early 20th century.
The word "placebo" has been used in many somewhat varying meanings; see below.
# Concept
Studies published in Proceedings of the National Academy of Sciences using advances in neuroscience (PET scans) have shown that placebos can noticeably reduce pain in humans. Researchers at Columbia and Michigan University have shown that the brains of volunteers who believed that what they were taking was pain medication were shown to be spontaneously releasing opioids, or natural pain relief.[4] According to that ABC report the Food and Drug Administration contends that as many as 75 percent of patients have had responses to sugar pills. It pointed out that all major clinical trials use placebo groups because the effect is significant and to be expected.
This effect has been known since the early 20th century. Generally, one third of a control group taking a placebo shows improvement, and Harvard’s Herbert Benson says that the placebo effect yields beneficial clinical results in 60–90% of diseases, including angina pectoris, bronchial asthma, herpes simplex, and duodenal ulcers.[5]
The following are some of the issues pointing to a fundamental problem:
- Ever since Beecher's 1955 study appeared,[6] it has been claimed that about one third of the therapeutic effect observed in a typical trial is attributable to the placebo effect. But this is not what Beecher showed at all. In the "meta-analytic" section of his paper he gave the proportion of subjects across 15 trials deemed to have "been satisfactorily relieved by placebo" as 35.2% +/- 2.2%. This, if anything, is an estimate of the frequency of 'placebo-responders' in the aggregate trial group, but says nothing about the magnitude of the effect.
- Beecher, intentionally or otherwise, gave currency to the idea that the placebo effects were roughly constant at around 35%, and that the term could be usefully applied to all those variables otherwise called "non-specific" contributors to therapeutic outcomes - the natural (and unknowable) course of diseases, regression to the mean, expectation effects, changes in effect and other unquantifiable psycho-somatic features of illness, beliefs and therapeutic communication, etc. If anything is clear from subsequent studies, it is that the placebo effect is not constant, but strikingly variable. Placebo response rates all the way from zero to 100% have been reported in virtually every clinical condition studied (the variation in Beecher's own series was 15–58%). The so-called effect appears to be both universal and utterly unpredictable.
- Beecher, who was concerned to promote the use of Randomised controlled trials (RCTs) in clinical research, made an unjustified assumption which is almost certainly false - that placebo effects in the intervention and control arms of a trial will be identical, or nearly so, and independent of the therapeutic effects. In the rationalization of RCTs which followed, this claim has never been rigorously defended, and in specific instances, can be easily refuted.[7]
- The original 1955 article of Beecher "The Powerful Placebo" claimed a 35% placebo effect in 15 studies. The original article was in 1997 re-analysed and "no evidence was found of any placebo effect in any of the studies" used by Beecher.[8] The claimed "effects" were produced by spontaneous improvement, fluctuation of symptoms, regression to the mean, additional treatment, conditional switching of placebo treatment, scaling bias, irrelevant response variables, answers of politeness, experimental subordination, conditioned answers, neurotic or psychotic misjudgment, psychosomatic phenomena, misquotation, etc.
- Kaptchuk has shown[9] that both the name and the concept of placebo were transferred from at least 200 years of use in clinical practice, in the decade following the second world war, to a new role required by the methodology of what was then the new discipline of 'clinical research'. Earlier usage corresponded to its Latin etymology - a harmless pill or potion given knowingly to patients who were either hard to please or hard to cure. The first clear example cited in the OED is from 1811. But during the post-war therapeutic revolution, it became the trashcan into which all the confounding factors that disturb therapeutic assessments were tipped. In Beecher's terms, it became a powerful if enigmatic distraction to researchers, whose results would be contaminated without rigorous procedures for its exclusion. Its modern use is therefore quite recent, and closely related to the adoption of the RCT as the methodological gold standard for trials of therapy.
- A considerable body of work has attempted to elucidate the 'mechanism' of the placebo effect - but without much success. Proposals ranging from 'suggestibility' and various other psychological hypotheses, to neuro-endocrine studies, and attribution of the effect to statistical artefacts, have turned out to be flawed in various ways, so that clinical researchers have no more idea of what is really going on in the control arms of their trials than did Hippocrates. It seems unlikely that this deeply unsatisfactory situation will be resolved by a new attempt to answer the old question; instead, as has been suggested by some of the most thoughtful students, we should expect to find that some part of the conceptual landscape in which this problematic entity resides must be reconstructed before it will come into focus. This view commends itself specially to those scholars who bring to the problem a perspective from outside the clinic - from medical anthropology, history of medicine, philosophy, and statistics.[10]
# Inertness
Although placebos are generally characterized as pharmacologically inert substances or formulations, sham treatments, or inactive procedures, they are only inert, sham, ineffective, or inactive in the particular sense that they have no known cause and effect relationship with any of the pre-designated, biochemical, physiological, behavioural, emotional and/or cognitive outcomes of the pharmacologically active and known-to-be-efficacious intervention that might have otherwise been applied (see below).
Placebos are inactive or ineffective treatments or formulations; however a patient may experience either a positive or negative clinical effect while taking one. When a placebo is administered to mimic a previously administered drug, it may also incur the same side effects as the prior authentic drug. Most of these effects are thought to be psychological in nature or due to other unrelated factors. Not all placebos are equally effective. A placebo that involves ingestion, injection, or incision is often more powerful than a non-invasive technique. Placebos administered by authority figures such as general practitioners and other experts may also be more powerful than when this psychological authority effect is absent.
They are, however, not inert, sham, or inactive in any other manner of speaking; and they may well, in and of themselves, generate considerable change within any given subject, at any given time, under any given circumstances. According to Shapiro:
Actually the question of inert versus active placebo is academic, because there is no such thing as an inactive substance. For example, distilled water injections can cause hemolysis and water intoxication. Ingestion of two 5-grain [325 mg] capsules of sacchari lactis [milk sugar], QID [quater in die, "four times a day"], for 30 years, can result in a weight gain of 30 pounds, so that even sugar can hardly be considered harmless, indifferent, or inert.
# Nocebo
In the opposite effect, a patient who disbelieves in a treatment may experience a worsening of symptoms. This effect, now called by analogy the "nocebo effect" (Latin nocebo = "I will harm") can be measured in the same way as the placebo effect, e.g., when members of a control group receiving an inert substance report a worsening of symptoms. The recipients of the inert substance may nullify the placebo effect intended by simply having a negative attitude towards the effectiveness of the substance prescribed, which often leads to a nocebo effect, which is not caused by the substance, but due to other factors, such as the patient's mentality towards his or her ability to get well, or even purely coincidental worsening of symptoms.
# Etymology
The word placebo is Latin for "I will please". It is in Latin text in the Bible (Psalm 114:1–9, Vulgate version), from where it became familiar to the public via the Office of the Dead church service. From that, a singer of Placebo (at funeral) became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer.
Whenever a placebo is requested in a medical prescription it may imply a statement by the prescribing doctor that "This patient has come to me pleading for a treatment which does not exist or which I cannot or will not supply; I will please him by giving him something ineffectual and claiming that it is effectual." It could also indicate a belief that the effect was due to a subconscious desire of the patient to please the doctor. Since the placebo effect is in the patient not the doctor this may be more self-consistent. Early usage of the term does not indicate why it was chosen.
## Obecalp
Sometimes a doctor who does this, says that the fake medicine is "Obecalp", which is "placebo" spelt backwards. [2] [3] (and many other links)
# Early use
Originally, a placebo was a substance that a well-meaning doctor would give to a patient, telling him that it was a powerful drug (e.g., a painkiller), when in fact it was nothing more than a sugar pill. Thus, Hooper's medical dictionary of 1811 says placebo is "an epithet given to any medicine adapted more to please than benefit the patient." The subsequent reduction of the patient's symptoms was attributed to the patient's faith in his doctor and hence his belief in the drug. (This category, particularly before the first Medicines Act was passed, may merge into fake medicines.)
# Modern clinical application
Experimenters typically use placebos in the context of a clinical trial, in which a "test group" of patients receives the therapy being tested, and a "control group" receives the placebo. It can then be determined if results from the "test" group exceed those due to the placebo effect. If they do, the therapy or pill given to the "test group" is assumed to have had an effect.
# Origin of term "placebo effect"
Perhaps Graves (1920) was the first to speak of the placebo effect, when he spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced".[11]
In 1933 (Evans and Hoyle) (using 90 subjects) and in 1937 (Gold, Kwit and Otto) (using 700 subjects) each published a study which compared the outcomes from the administration of an active drug and a dummy simulator (which both research groups called a placebo) in the same trial. Neither experiment displayed any significant difference between drug treatment and placebo treatment; leading the researchers to conclude that the drug exerted no specific effects in relation to the conditions being treated.
In 1946, the Yale biostatistician and physiologist E. Morton Jellinek was the first to speak of either a "placebo reaction" or a "placebo response". He speaks of a "response to placebo" (p.88), those who "responded to placebo" (p.88), a "reaction to placebo" (p.89), and of "reactors to placebo" (p.90). From this, it is obvious that, to Jellinek, the terms "placebo response" and "placebo reaction"—or the terms "placebo responder" and "placebo reactor"—were identical and interchangeable.
The general literature commonly misattributes the term "placebo effect" to Henry K. Beecher's 1955 paper The Powerful Placebo, where, however, he only speaks of placebo effects when he is contrasting them with drug effects; otherwise, he always speaks of "placebo reactors" and "placebo non-reactors".
Beecher (1952), Beecher, Keats, Mosteller, and Lasagna (1953), Beecher (1959), consistently speak of "placebo reactors" and "placebo non-reactors"; they never speak of any "placebo effect". Beecher (1970) simply speaks of "placebos".
# Isolation of cause
According to Kleijnen and his colleagues,[12] healing is an interactive process between three influences:
- (1) the self-healing properties of the subject.
- (2) the non-specific effects induced by the presence of the therapist and the therapeutic setting.
- (3) the specific effects of the physical or pharmacological therapeutic interventions.
These effects are not isolated mutually-exclusive effects and, rather than just adding, they may help or hinder each other to various degrees.[13] Also, Hyland (2003, p.348) notes that, in cases where “contextual factors contribute to a strong placebo response”, due to “the potentiating or adjunctive effect of the placebo response”, placebos can be used “potentiate the effect of an active treatment” that would have otherwise been far less efficacious.
From this notion that a “drug” has a specific treatment effect (i.e., the effect for which it has been administered), Perlman (2001, p.283) draws attention to three other treatment effects:
- non-specific effects: these are the side effects (“which are usually considered deleterious”);
- unintended effects: these are the placebo effects (“which… are still considered to be for the most part uncontrolled and unscientific”); and
- serendipitous effects: these are the “serendipitous effects of being in therapy, such as [the] organizing effects of the therapeutic structure, inadvertent role modelling, outside knowledge of the therapist, chance remarks or encounters, and the influence of auxiliary personnel”.
In pursuit of establishing causation, the question “Who does what, with which, and to whom?” is central to task of identifying what are:
- specific effects (those for which the treatment was administered),
- non-specific effects (predictable "side effects"),
- unintended effects (i.e., the placebo responses),
- serendipitous effects of treatment (i.e., effects of the subject just being "in therapy"); Perlman (2001)(p.283) in discussing this suggests these as examples:
the "organizing effects of the therapeutic structure",
"inadvertent role modeling",
"outside knowledge of the therapist",
"chance remarks or encounters",
"the influence of auxiliary personnel" ("this category includes doormen, receptionists, cashiers, secretaries, security guards, janitors, and child care attendants", p.287).
- the "organizing effects of the therapeutic structure",
- "inadvertent role modeling",
- "outside knowledge of the therapist",
- "chance remarks or encounters",
- "the influence of auxiliary personnel" ("this category includes doormen, receptionists, cashiers, secretaries, security guards, janitors, and child care attendants", p.287).
Gaddum (1954) also recognizes that "changes in the incidence or severity of diseases in a hospital may be due to changes in the diet or changes in the nurses, which happen to coincide with the introduction of a new treatment" (pp.195–196).
In experiments with the common cold by Gold, Kwit & Otto (1937), in accounting for why those who received the placebo drug often experienced considerable benefit, Gold and his colleagues supposed that other, non-drug-related factors may have made a significant contribution to the apparent efficacy of the supposedly active drug, such as:
- Spontaneous variations in the course of the pain.
- Change in the weather.
- Change of occupation or amount of work.
- Change of diet.
- Change in eating habits with increase in the amount of rest before and after meals.
- Condition of the bowels.
- Emotional stress.
- Change in domestic affairs.
- Confidence aroused in the treatment.
- Encouragement afforded by any new procedure.
- A change of the medical adviser.[14]
Also, due to the difficulty in ascribing causation, many phenomena overlap with, and are thus misattributed to, subjects' placebo responses (the phenomena are known as "confounders" or "lurking variables", such as:
- Natural termination of the disease process.
- Regression to the mean.
- Cyclical presentation of the disease.
- Errant diagnosis or prognosis.
- Temporary improvement confused with cure.
The placebo effect may be partly determined by genetics.[15]
Open-label placebo vs double-blind placebo.[16]
## Physician-patient relationship
Atributes of the physician, patient, and their relationship are important[17][18].
# Technical challenges and pitfalls
## Preventing subjects from recognizing a placebo
Appropriate use of a placebo in a clinical trial often requires or at least benefits from a double-blind study design, which means that neither the experimenters nor the subjects know which subjects are in the "test group" and which are in the "control group".
## Adherence to use of a placebo
The Coronary Drug Project was intended to study the safety and effectiveness of drugs for long-term treatment of coronary heart disease in men. Those in the placebo group who adhered to the placebo treatment (took the placebo regularly as instructed) showed nearly half the mortality rate as those who were not adherent.[19]
A similar study of women similarly found survival was nearly 2.5 times greater for those who adhered to their placebo.[20] This apparent placebo effect may be caused by:
- The psychological effect of adhering to the protocol, i.e. genuine placebo effect.
- Being healthy enough to follow the protocol.
- Compliant people being more diligent and scrupulous in all aspects of their lives.
## Need for psychoactive placebo
Because a belief that one has received the active drug can produce a markedly heightened placebo effect, it is often necessary to use a psychoactive placebo in clinical trials; i.e., a drug that produces enough physical effects to encourage the belief in the control and experimental groups that they have received the active drug.
A psychoactive placebo was used in the Marsh Chapel Experiment: a double-blind study, in which the experimental group received psilocybin while the control group received a large dose of niacin, a substance that produces noticeable physical effects.
Walter Pahnke in 1962 described his Marsh Chapel Experiment in his unpublished Ph.D. dissertation "Drugs and Mysticism: An Analysis of the Relationship between Psychedelic Drugs and the Mystical Consciousness, and submitted it in 1963, for his Ph.D. in Religion and Society at Harvard University; Timothy Leary was the principal academic advisor for his dissertation. In it, Pahnke wrote of administering capsules that contained 30mg of psilocybin extracted from psychoactive mushrooms, and contrasting their effects with those of psychoactive placebos, which contained the chemical niacin in such a dosage that it produced very significant physiological responses. It was intended that these responses would lead the control subjects to believe they had received the psychoactive drug.
The term "psychoactive placebo" is rare in the literature; but, when it is used, it always denotes a placebo of this type. For example, "Neither the experienced investigator nor the naive [subject] is easily fooled on the matter of whether he has received a psychedelic substance or merely a psychoactive placebo such as amphetamine." (Harman, McKim, Mogar, Fadiman & Stolaroff, 1966, p.215)
# Use in clinical trials
Placebo simulators are a standard control component of most clinical trials which attempt to make some sort of quantitative assessment of the efficacy of new medicinal drugs; It is a view held by many "that placebo-controlled studies often are designed in such a way that disadvantages the placebo condition"[21] and, generally speaking, for a drug to be put on the market, it must be significantly more effective than its placebo counterpart.
According to Yoshioka (1998), the first-ever randomized clinical trial was the trial conducted by the Medical Research Council (1948) into the efficacy of streptomycin in the treatment of pulmonary tuberculosis.There were two test groups in this trial
- those "treated by streptomycin and bed-rest", and
- those "[treated] by bed-rest alone" (the control group).
What made this trial exceptional was that the subjects were randomly allocated to their test groups. The up-to-that-time practice was to allocate subjects alternately to each group, based on the order in which they presented for treatment. This practice was considered to be extremely biased, because those admitting each patient knew to which group that patient would be allocated (and it was considered that the decision to admit or not admit a specific patient might be influenced by the experimenter's knowledge of the nature of their illness, and their knowledge of the group to which the alternate allocation demanded they would occupy).
In recent times, the practice of using an additional natural history group as the trial's so-called "third arm" has emerged; and trials are conducted using three randomly-selected equally-matched trial groups, David (1949, p.28) wrote: "... it is necessary to remember the adjective ‘random’ [in the term ‘random sample’] should apply to the method of drawing the sample and not to the sample itself.".
- The Active drug group (A): who receive the active test drug.
- The Placebo drug group (P): who receive a placebo drug that simulates the active drug.
- The Natural history group (NH): who receive no treatment of any kind (and whose condition, therefore, is allowed to run its natural course).
The outcomes within each group are observed, and compared with each other, allowing us to measure:
- The efficacy of the active drug's treatment: the difference between A and NH (i.e., A-NH).
- The efficacy of the entire treatment process alone: the difference between P and NH (i.e., P-NH).
- The efficacy of the active drug's active ingredient: the difference between A and P (i.e., A-P).
- The magnitude of the placebo response: the difference between P and NH (i.e., P-NH).
Note that, depending upon the focus of your interest, the value of P-NH can either indicate the efficacy of the entire treatment process or the magnitude of the "placebo response".
The results of these comparisons then determine whether or not a particular drug is considered efficacious.
In recent times, as the demands for the scientific validation of the various claims that are made for the efficacy of various so-called "talking therapies" (such as hypnotherapy, psychotherapy, counselling, and non-drug psychiatry) has significantly increased, there is continuing controversy over what might or might not be an appropriate placebo for such therapeutic treatments.
In 2005, the Journal of Clinical Psychology, an eminent peer-reviewed journal (founded in 1945), devoted an entire issue to the question of "The Placebo Concept in Psychotherapy", and contained a wide range of articles that made many valuable contributions to this overall discussion.
# Placebo response as an index
In certain clinical trials of particular drugs, it may happen that the level of the "placebo responses" manifested by the trial's subjects are either considerably higher or lower (in relation to the "active" drug's effects) than one would expect from other trials of similar drugs. In these cases, with all other things being equal, it is entirely reasonable to conclude that:
- the degree to which there is a considerably higher level of "placebo response" than one would expect is an index of the degree to which the drug's active ingredient is not efficacious.
- the degree to which there is a considerably lower level of "placebo response" than one would expect is an index of the degree to which, in some particular way, the placebo is not simulating the active drug in an appropriate way.
However, in particular cases such as the use of Cimetidine to treat ulcers (see below), a significant level of placebo response can also prove to be an index of how much the treatment has been directed at a wrong target.
# Trials
"Heroic medicine" had begun to fall from favour long before research scientists such as Robert Koch, Louis Pasteur, Frederick Hopkins and Casimir Funk demonstrated that the presence or the absence of specific agents could cause specific diseases, and long before the chemical laboratory orientation of Abraham Flexner’s 1910 Flexner Report had evolved into the evidence-based medicine of the 1970s. As the earliest precursors of modern, scientific, conventional medicine began to emerge, medical scholars began to routinely question:
- the principles of their medical diagnosis and prognosis,
- the efficacy of their conventional medical practices,
- the correctness of their current anatomical, physiological and neurological knowledge, and
- the true scientific status of the drugs and therapies in their pharmacopoeia.
In many cases, active agents were identified in supposedly efficacious treatments; but it was found that some treatments had no efficacy whatsoever; and, regardless of how much they were accepted in the medical profession, or what they were supposed to do, they were medically useless.
Many, such as Pepper (1945, p.410) would strongly argue that, before the Countess of Chinchón learned of the medicinal properties of cinchona bark (perhaps the first time a real active ingredient had been isolated and identified), "there was [no] basis for terming anything a placebo".
The aim of a clinical trial is to determine what treatments, delivered in what circumstances, to which patients, in what conditions, are the most efficacious; as well to obtain objective evidence of what treatments are efficacious and also specific,[22] or are intentionally efficacious and also specific.[23]
Gaddum (1953, p.195) wrote: "The first object of a therapeutic trial is to discover whether the patients who receive the treatment under investigation are cured more rapidly, more completely or more frequently, than they would have been without it."
## 1747: remedies for scurvy
In 1747, James Lind (1716–1794), the Naval Surgeon on HMAS Salisbury, conducted what was most likely the first-ever clinical trial when he investigated the efficacy of citrus fruit in cases of scurvy.
He randomly divided twelve scurvy patients, whose "cases were as similar as I could have them", into six pairs. Each pair was given a different remedy. Lind’s approach can still be seen in the way that the comparative efficacy of various treatments for particular sorts of cancer are determined, by examining and comparing the five year survival rates of those who have been treated with each of the different interventions. He noted that the pair who had been given the oranges and lemons were so restored to health within six days of treatment that one of them returned to duty, and the other was well enough to attend the rest of the sick.[24]
According to Lind’s 1753 Treatise on the Scurvy in Three Parts Containing an Inquiry into the Nature, Causes, and Cure of the Disease, Together with a Critical and Chronological View of what has been Published of the Subject, the remedies were:
- one quart of cider per day,
- twenty-five drops of elixir vitriol (sulfuric acid) three times a day,
- two spoonfuls of vinegar three times a day,
- a course of sea-water (half a pint every day),
- two oranges and one lemon each day,
- an electuary (Dunn, 1997, p.F65).
Gaddum (1954, p.196) wrote that the electuary had been recommended to Lind by a hospital surgeon, and that it contained garlic, mustard, balsam of Peru, and myrrh.
## 1784: animal magnetism
In 1784, the French Royal Commission looked into the existence of animal magnetism and investigated the practices of Charles d’Eslon (1739–1786), comparing the effects of his allegedly "magnetized" water with that of plain water.[25]
It did not examine the practices of Franz Mesmer, but examined the significantly different practices of his associate Charles d’Eslon.
See animal magnetism for more information.
## 1799: Perkins tractors
In 1799, John Haygarth investigated the efficacy of medical instruments called "Perkins tractors", by comparing the results from dummy wooden tractors with a set of allegedly "active" metal tractors.[26]
## 1863: placebo compared with active treatment
In 1863 Austin Flint (1812–1886) conducted the first-ever trial that directly compared the efficacy of a dummy simulator with that of an active treatment; although Flint's examination did not compare the two against each other in the same trial. Even so, this was a significant departure from the (then) customary practice of contrasting the consequences of an active treatment with what Flint described as "the natural history of [an untreated] disease".[27]
Flint’s paper is the first time that either of the terms "placebo" or "placeboic remedy" were ever used to refer to a dummy simulator in a clinical trial.
... to secure the moral effect of a remedy given specially for the disease, the patients were placed on the use of a placebo which consisted, in nearly all of the cases, of the tincture of quassia, very largely diluted. This was given regularly, and became well known in my wards as the placeboic remedy for rheumatism.
Flint (1863, p.21) treated 13 hospital inmates who had rheumatic fever; 11 were "acute", and 2 were "sub-acute". He then compared the results of his dummy "placeboic remedy" with that of the active treatment’s already well-understood results. (Flint had previously tested, and reported on, the active treatment’s efficacy.) There was no significant difference between the results of the active treatment and his "placeboic remedy" in 12 of the cases in terms of disease duration, duration of convalescence, number of joints affected, and emergence of complications (pp.32–34). In the thirteenth case, Flint expressed some doubt as to whether the particular complications that had emerged (namely, pericarditis, endocarditis, and pneumonia) would have been prevented if that subject had been immediately given the "active treatment" (p.36).
## 1946: a headache remedy ingredient
In post-World War II 1946, pharmaceutical chemicals were in short supply. One U.S. headache remedy manufacturer sold a drug that was composed of three ingredients: a, b, and c. Chemical b was in short supply.
Jellinek was asked to test whether or not the headache drug's overall efficacy would be reduced if ingredient b was missing.
Jellinek set up a complex trial involving 199 subjects, all of whom suffered from "frequent headaches". (Originally there were 200 subjects, but one did not complete the trial.) The subjects were randomly divided into four test groups. He prepared four test drugs, involving various permutations of the three drug constituents, with a placebo as a scientific control. The structure of this trial is significant because, in those days, the only time placebos were ever used "was to express the efficacy or non-efficacy of a drug in terms of "how much better" the drug was than the "placebo". (Jellinek (1946), p.88. Note that the trial conducted by Austin Flint is an example of such a drug efficacy vs. placebo efficacy trial.) The four test drugs were identical in shape, size, colour and taste:
- Drug A: contained a, b, and c.
- Drug B: contained a and c.
- Drug C: contained a and b.
- Drug D: a 'simulator', contained "ordinary lactate".
Each time a subject had a headache, they took their group’s designated test drug, and recorded whether their headache had been relieved (or not). Although "some subjects had only three headaches in the course of a two-week period while others had up to ten attacks in the same period", the data showed a "great consistency" across all subjects (Jellinek, 1946, p.88). Every two weeks the groups’ drugs were changed; so that by the end of eight weeks, all groups had tested all the drugs.
The stipulated drug (i.e., A, B, C, or D) was taken as often as necessary over each two-week period, and the two week sequences were:
- A, B, C, D
- B, A, D, C
- C, D, A, B
- D, C, B, A.
Each group took a test remedy for two weeks. The trial lasted eight weeks, and by the end of the trial all groups had taken each test drug for two weeks (although each group had taken them in a different sequence). Over the entire population of 199 subjects, 120 of the subjects responded to the placebo, and 79 did not; i.e., there were 120 "subjects reacting to placebo" and 79 "subjects not reacting to placebo".[28]
At first glance there was no difference between the self-reported "success rates" of Drugs A, B, and C (84%, 80%, and 80% respectively) (the "success rate" of the simulating placebo Drug D was 52%); and, from this, it appeared that ingredient b was completely unnecessary.
However, in quite a remarkable way, the trial eventually did demonstrate that ingredient b did make a significant contribution to the remedy’s efficacy. Examining his data more closely, Jellinek discovered that there was a very significant difference in responses between the 120 placebo-responders and the 79 non-responders. The 79 non-responders' reports showed that if they were considered as an entirely separate group, there was a significant difference the "success rates" of Drugs A, B, and C: viz., 88%, 67%, and 77%, respectively. And because this significant difference in relief from the test drugs could only be attributed to the presence or absence of ingredient b, he concluded that ingredient b was essential (thus contradicting his initial conclusion, derived from the comparison between the "success rates" for all test subjects, that Drugs A, B, and C were equally efficacious).
There were two further repercussions from this trial:
- Jellinek (p.90), having identified 120 "placebo reactors", went on to suppose that all of them may have been suffering from either "psychological headaches" (with or without attendant "hypochondriasis" (p.90)) or "true physiological headaches [which were] accessible to suggestion". Thus, according to this view, the degree to which a "placebo response" is present tends to be an index of the psychogenic origins of the condition in question.[29]
- It indicated that, whilst any given placebo was inert, a responder to that particular placebo may be responding for a wide number of reasons unconnected with the drug's active ingredients; and, from this, it could be important to pre-screen potential test populations, and treat those manifesting a placebo-response as a special group, or remove them altogether from the test population.
## 1983: cimetidine
This test wrongly seemed to show that cimetidine was a placebo, because they did not know that the bacterium Helicobacter pylori was sometimes present and interfering with results.
In 1983 medical anthropologist Daniel Moerman conducted a meta-study of 31 placebo-controlled trials of the gastric acid secretion inhibitor drug Cimetidine in the treatment of gastric or duodenal ulcers. His meta-study revealed that the placebo treatments were, in many cases, just as effective in treating ulcers as the active drug: of the 1692 patients treated in the 31 trials, 76% of the 916 treated with the drug were "healed", and 48% of the 776 treated with placebo were "healed". These results were confirmed by the direct post-treatment endoscopy of the treated area. He also found that German placebos were "stronger" than others; and that, overall, different physicians evoked quite different placebo responses in the same clinical trial (p.15).
Further examination revealed that many of these trials had been conducted in such a way that the gap between the active drugs and the placebo controls was "not because [the trials' constituents] had high drug effectiveness, but because they had low placebo effectiveness" (p.13).
In some trials, placebos were effective in 90% of the cases, whilst in others the placebos were only effective in 10% of the cases. Moerman argues that "what is demonstrated in [these] studies is not enhanced healing in drug groups, but reduced healing in placebo groups" (p.14).
Moerman also noted the results of two studies (one conducted in Germany, the other in Denmark), which examined "ulcer relapse in healed patients". Each study showed that the rate of relapse amongst those "healed" by the active drug treatment was five times that of those "healed" by the placebo treatment (pp.14–15). This led Moerman to remark: “we may be able to go so far as to say that while [the active drug] “heals” ulcers, placebo treatment can “cure” ulcer disease” (p.14).
These results of a 90% placebo response rate, and a placebo-healed relapse rate 20% that of the active drug seems to indicate that the drug Cimetidine was not effective in inhibiting gastric acid secretion.
However, as we now know, the majority of gastric or duodenal ulcers are not due to excessive gastric acid secretion caused by stress or spicy food, but are due to the bacterium Helicobacter pylori, it is highly significant that this high response rate and low relapse rate can now be interpreted otherwise: it was indicating that the drug's prescribers had chosen the wrong target for their therapeutic intervention (and, as a consequence, we now know that they had chosen what might be termed an "inappropriate target but correct drug", rather than a "correct target but inappropriate drug" as was first supposed).
## Placebo-controlled studies
Beecher (1955) reported that about a quarter of patients who were administered a placebo, for example against back pain, reported a relief or diminution of pain. Remarkably, not only did the patients report improvement, but the improvements themselves were often objectively measurable, and the same improvements were typically not observed in patients who did not receive the placebo.
Because of this effect, government regulatory agencies approve new drugs only after tests establish not only that patients respond to them, but also that their effect is greater than that of a placebo (by way of affecting more patients, by affecting responders more strongly or both). Such a test or clinical trial is called a placebo-controlled study.
Because a doctor's belief in the value of a treatment can affect his or her behaviour, and thus what his or her patient believes, such trials are usually conducted in "double-blind" fashion: that is, not only are the patients made unaware when they are receiving a placebo, the doctors are made unaware too. Recently, it has even been shown that "mock" surgery can have similar effects, and so some surgical techniques must be studied with placebo controls (rarely double blind, due to the difficulty involved). To merit approval, the group receiving the experimental treatment must experience a greater benefit than the placebo group.
Nearly all studies conducted this way show some benefit in the placebo group. For example, Khan published a meta-analysis of studies of investigational antidepressants and found a 30% reduction in suicide and attempted suicide in the placebo groups and a 40% reduction in the treated groups. (Khan 2000) However, studies generally do not include an untreated group, so determining the actual size of the placebo effect, compared to totally untreated patients, is difficult.
# Effect on various symptoms
## Pain
Placebo may bae able to reduce pain according to a systematic review by the Cochrane Collaboration.[30] More recent studies confirm this[31] and suggest that placebos that are perceived to be more expensive are more effective.[32]
The effect is more pronounced with pre-existing pain than with experimentally induced pain. People can be conditioned to expect analgesia in certain situations. When those conditions are provided to the patient, the brain responds by generating a pattern of neural activity that produces objectively quantifiable analgesia. (Benedetti 2003, Wager 2004)
Evans argued that the placebo effect works through a suppression of the acute phase response, and as a result does not work in medical conditions that do not feature this. (Evans 2005) The acute phase response consists of inflammation and sickness behaviour:
- Four classic signs of ‘inflammation’: tumor, rubor, calor, and dolor – (Latin for "swelling, redness, heat, and pain").
- Sickness behaviour: lethargy, apathy, loss of appetite, and increased sensitivity to pain.
## Depression
A brain-imaging study found that depressed patients who responded to the placebo effect showed changes in cerebral blood flow, which were similar to the changes in brain function seen in patients who responded to anti-depressant medication. (Leuchter 2002) Other studies argue that up to 75% of the effectiveness of anti-depressant medication is due to the placebo-effect rather than the treatment itself. (Khan 2000)
## Withdrawal symptoms on discontinuation
The Women's Health Initiative study of hormone replacement therapy for menopause was discontinued after participants still in the program had been taking either hormones or placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 40.5% of those on placebo compared to 63.3% of those on hormone replacement. Pain and stiffness (musculoskeletal symptoms) were the most frequently reported symptoms in both the placebo group (22.2%) and the hormone group (36.8%), exceeding other symptoms by more than 10%. Of those reporting pain and stiffness, 54.7% in the hormone group and 38.3% in the placebo group had these symptoms at the onset of therapy. Tiredness
was the second most frequently reported withdrawal symptom (21.3% hormone, 11.6% placebo) and hot flashes/night sweats the third (21.2% hormone, 4.8% placebo).[33] Only the vasomotor symptoms (hot flashes/night sweats) were acknowledged to be verified effects of menopause by a 2005 National Institutes of Health panel.[34]
These results may indicate some learned response concerning which withdrawal symptoms appear in a placebo group as well as in the subjects who received therapy, with a greater effect on pain and tiredness than on vasomotor symptoms.
## Objective and subjective effects
Hrobjartsson and Götzsche published a study in 2001 and a follow-up study in 2004 questioning the nature of the placebo effect. (Hrobjartsson 2001, Hrobjartsson 2004) They performed two meta-analyses involving 156 clinical trials in which an experimental drug or treatment protocol was compared to a placebo group and an untreated group, and specifically asked whether the placebo group improved compared to the untreated group. Hrobjartsson and Götzsche found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group. Similarly, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could only be documented in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have "powerful clinical effects," (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from bias.
These results suggest that the placebo effect is largely subjective. This would help explain why the placebo effect is easiest to demonstrate in conditions where subjective factors are very prominent or significant parts of the problem. Some of these conditions are headache, stomachache, asthma, allergy, tension, and the experience of pain, which is often a significant part of many mild and serious illnesses.
# Mechanism for the effect
It is universally accepted that, for a placebo response to occur, the subject must believe an effective medication (or other treatment) has been administered to them, but must not know it is an ineffective placebo. This is quite different from the case of an "active drug", where the drug response is generated even in the case of covert administration, in other words regardless of whether the patient knows or doesn't know they have received any medication.
The question of just how and why placebo responses are generated is not an abstract theoretical issue; it has wide implications for both clinical practice and the experimental evaluation of therapeutic interventions.
In recent times, three different hypotheses have been offered to account for these placebo responses — i.e., "expectancy theory" and 'classical conditioning" and motivation — which, whilst emphasizing different factors, are not mutually exclusive and, in fact, overlap to a certain extent.
## Expectancy effect
The subject-expectancy effect attributes the placebo effect to conscious or unconscious manipulation by patients in reporting improvement. Hrobjartsson and Götzsche argued in their article, "Most patients are polite and prone to please the investigators by reporting improvement, even when no improvement was felt." Subjective bias can also be unconscious, where the patient believes he is improving as a result of the attention and care he has received.
## Conditioning
Classical conditioning is a type of associative learning where the subject learns to associate a particular stimulus with a particular response. In this case the stimulant is the substance perceived as medicine but is the placebo, and the response is the relief of symptoms. It is difficult to tell the difference between conditioning and the expectancy effect when the outcome is subjective and reported by the patient. However, conditioning can result in measurable biological changes similar to the changes seen with the real treatment or drug. For example, studies showing that placebo treatments result in changes in brain function similar to the real drug are probably examples of conditioning resulting in objectively measurable results. (Sauro 2005, Wager 2004, Arnaldo 2002)
## Motivation
Motivational explanations of the placebo effect have typically considered the placebo effect to be an outcome of one’s desire to feel better, reduce anxiety, or cooperate with an experimenter or health care professional (Price et al. 1999, Margo 1999). The motivational perspective is supported by recent research showing that nonconscious goals for cooperation can be satisfied by confirming expectations about a treatment (Geers et al. 2005).
## Role of endogenous opiates
The discovery in 1975 of Endogenous opiates alias endorphins (substances like opiates but naturally produced in the body) have changed matters in investing placebo effect. When patients who claimed to experience pain relief after receiving a placebo were injected with naloxone (a drug that blocks the effects of opiates), their pain returned, suggesting that the placebo effect may be partly due to psychological reaction causing release of natural opiates. (Sauro 2005)
# Biological substrates of the placebo response
A "placebo response" can amplify, diminish, nullify, reverse or, even, divert the action of an "active" drug.
Because a "placebo response" is just as significant in the case of an "active" drug as it is in the case of an "inert" dummy drug, the more that we can discover about the mechanisms that produce "placebo responses", the more that we can enhance their effectiveness and convert their potential efficacy into actual relief, healing and cure.
Recent research[35] strongly indicates that a "placebo response" is a complex psychobiological phenomenon, contingent upon the psychosocial context of the subject, that may be due to a wide range of neurobiological mechanisms (with the specific response mechanism differing from circumstance to circumstance).
The very existence of these "placebo responses" strongly suggest that "we must broaden our conception of the limits of endogenous human control";[36] and, in recent times, researchers in a number of different areas have demonstrated the presence of biological substrates, unique brain processes, and neurological correlates for the "placebo response":
- 2001: de la Fuente-Fernández and colleagues reported their PET scan findings on test subjects with Parkinson's disease.
- 2002: Petrovic and colleagues reported their PET scan findings on test subjects in a trial of opioid analgesia.
- 2002: Mayberg and colleagues reported their PET scan findings on test subjects with unipolar depression.
- 2004: Wager and colleagues reported their fMRI scan findings on test subjects in a trial of placebo analgesia.
- 2004: Lieberman and colleagues reported their PET scan findings on test subjects with Irritable bowel syndrome.
- 2006: Bingel and colleagues reported their fMRI scan findings on test subjects in a trial of placebo analgesia.
- 2006: Zubieta and colleagues reported their PET scan findings on test subjects in a trial of placebo analgesia.
- 2006: Sarinopoulos and colleagues reported their fMRI scan findings on test subjects in a trial neural responses to a highly aversive bitter taste.
A complex fMRI-centred study by McClure, et al. (2004) on the brain responses of subjects who had previously expressed a preference for one or other of the similar soft drinks Pepsi and Coca-Cola, demonstrated that "brand information", which "significantly influences subjects’ expressed preferences", is processed in an entirely different brain area from the area activated in blind taste tests (when their "preferences are determined solely from sensory information").[37] This supports the claim that there are unconscious brain processes that activate the "placebo response".
# Ethical challenges and concerns
Bioethicists have raised diverse concerns on the use of placebos in modern medicine and research. These have been largely incorporated into modern rules for the use of placebos in research but some issues remain subject to debate. The ethics of prescribing placebos in medical practice is highly debated. Some practitioners argue that the use of placebos is sometimes justified because it will do no harm and may do some good. With the publication of studies by Hróbjartsson and Götzsche and others, the proposition that placebos may do some good is under fire.
- Disclosure. Rules that govern modern clinical trials insist on full disclosure to subjects who take part. Today, subjects are told that they may receive the drug being tested or they may receive the placebo.
- Balancing Treatment vs. Research Objectives. Ethicists have also raised concerns on the use of placebos in those circumstances in which a standard treatment exists unless there are genuine doubts of the effectivity of such standard treatment. If standard treatments exist for the disease being studied in clinical trials, a standard treatment is always used in place of a placebo for serious diseases. In research experimental studies, the method of establishing a proper control group to eliminate the placebo effect has also been difficult, particularly for surgical and therapy interventions that are not pharmaceutical in nature. Notably, there has been much debate of whether to use a placebo pill or conduct a sham procedure as a control.
Most of these concerns have been addressed in the modern conventions for the use of placebos in research; however, some issues remain subject to debate.
From the time of the Hippocratic Oath questions of the ethics of medical practice have been widely discussed, and codes of practice have been gradually developed as a response to advances in scientific medicine.
The Nuremberg Code, which was issued in August 1947, as a consequence of the so-called Doctors' Trial which examined the human experimentation conducted by Nazi doctors during World War II, offers ten principles for legitimate medical research, including informed consent, absence of coercion, and beneficence towards experiment participants.
In 1964, the World Medical Association issued the Declaration of Helsinki,[4] which specifically limited its directives to health research by physicians, and emphasized a number of additional conditions in circumstances where "medical research is combined with medical care".
The significant difference between the 1947 Nuremberg Code and the 1964 Declaration of Helsinki is that the first was a set of principles that was suggested to the medical profession by the "Doctors’ Trial" judges, whilst the second was imposed by the medical profession upon itself.
Paragraph 29 of the Declaration makes specific mention of placebos:
29. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.
In 2002, World Medical Association issued the following elaborative announcement:
Note of clarification on paragraph 29 of the WMA Declaration of HelsinkiThe WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:
All other provisions of the Declaration of Helsinki must be adhered to, especially the need for appropriate ethical and scientific review.
In addition to the requirement for informed consent from all drug-trial participants, it is also standard practice to inform all test subjects that they may receive the drug being tested or that they may receive the placebo.
A poll of 679 American internists and rheumatologists in the fall of 2008 revealed that approximately half of the physicians routinely prescribe placebos to their patients. Pain relievers and vitamins were the most frequently prescribed placebos, but many doctors also reported prescribing antibiotics and sedatives. The finding raised ethical concerns over informed consent and trust in the doctor-patient relationship as only 5 percent of the doctors revealed to their patients that the treatment was some form of placebo. Full results of the study were published in BMJ.[38]
# Doctor-patient relationship
A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the past year. The most frequently prescribed placebos were antibiotics for viral infections, and vitamins for fatigue. Specialists and hospital-based physicians reported much lower rates of placebo use. (Hrobjartsson 2003) A 2004 study in the British Medical Journal of physicians in Israel found that 60% used placebos in their medical practice, most commonly to "fend off" requests for unjustified medications or to calm a patient. Of the physicians who reported using placebos, only 15% told their patients they were receiving placebos or non-specific medications. (Nitzan 2004) An accompanying editorial stated,
The placebo effect, thought of as the result of the inert pill, can be better understood as an effect of the relationship between doctor and patient. Adding the doctor's caring to medical care affects the patient's experience of treatment, reduces pain, and may affect outcome. This survey makes it clear that doctors continue to use placebos, and most think they help.
The editorial suggested there were problems with Hróbjartsson and Götzsche's methods and argued that their results show that placebos can't cure everything, but don't prove that the placebo effect cures nothing. The editorial concluded, "We cannot afford to dispense with any treatment that works, even if we are not certain how it does." (Spiegel 2004)
The editorial prompted responses on both sides of the issue.
- Critics of the practice responded that it is unethical to prescribe treatments that don't work, and that telling a patient that a placebo is a real medication is deceptive and harms the doctor-patient relationship in the long run. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions.
- Defenders of the use of placebos suggested that placebos do not work in clinical trials because the subjects know they might be getting a placebo, but do work in medical practice where the patient believes he or she is getting an active drug. Other writers pointed to the empirical data showing that placebos can have measurable biological effects, especially in pain relief (see above), or argued that the use of a placebo to "please the patient" fosters real healing as part of a caring doctor-patient relationship. (Barfod 2005, Di Blasi 2005)
BMJ posted a series of responses to Dr. Spiegel's editorial online in their rapid response section. Selected responses were published in later issues of the Journal.
In addition, there are the impracticalities of placebos:
- Roughly only 30% of the population seems susceptible to placebo effects, and it is not possible to determine ahead of time for whom a placebo will work and for whom it will not.
- All placebo effects eventually wear off, thus making the placebo effect impractical for long term or chronic medical matters.
- Patients rightfully want immediate relief or improvement from their illness or symptoms. A non-placebo can often provide that, while a placebo might not.
- Legitimate doctors and pharmicists could open themselves up to charges of fraud since sugar pills would cost pennies or cents for a bottle, but the price for a "real" medication would be have to be charged to avoid making the patient suspicious.
- Unscrupulous medical practitioners could swindle patients with fake surgeries and sugar pills, then later claim that they only meant to help their patients by using "placebos".
About 25% of physicians in both the Danish and Israeli studies used placebos as a diagnostic tool to determine if a patient's symptoms were real, or if the patient was malingering. Both the critics and defenders of the medical use of placebos agreed that this was unethical. The British Medical Journal editorial said, "That a patient gets pain relief from a placebo does not imply that the pain is not real or organic in origin...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."
The placebo administration may prove to be a useful treatment in some specific cases where recommended drugs can not be used. For example, burn patients who are experiencing respiratory problems cannot often be prescribed opioid (morphine) or opioid derivatives (pethidine), as these can cause further respiratory depression. In such cases placebo injections (normal saline, etc.) are of use in providing real pain relief to burn patients if they (those not in delirium) are told that are being given a powerful dose of painkiller.
There is general agreement that placebo control groups are an important tool for controlling for several types of possible bias, including the placebo effect, in double blind clinical trials.
The placebo effect is an active area of research and discussion and it is possible that a clear consensus regarding the use of placebos in medical practice will emerge in the future.
# Use as morale-boosters
Hooper’s (1811) Quincy’s Lexicon-Medicum defines placebo as "an epithet given to any medicine adapted more to please than benefit the patient".
In the practice of medicine it had been long understood that, as Ambroise Paré (1510–1590) had expressed it, the physician’s duty was to "cure occasionally, relieve often, console always" ("Guérir quelquefois, soulager souvent, consoler toujours").
According to Jewson, eighteenth century English medicine was gradually moving away from the patient having a considerable interaction with the physician—and, through this consultative relationship, having an equal influence on the construction of the physician’s therapeutic approach—and it was gradually moving towards that of the patient being the recipient of a far more standard form of intervention that was determined by the prevailing opinions of the medical profession of the day.[39]
Jewson characterizes this as parallel to the changes that were taking place in the manner in which medical knowledge was being produced; namely, a transition all the way from "bedside medicine", through "hospital medicine", to "laboratory medicine".[40]
For more on the effect of the development of various types of medical technology see Medical sign#Increased reliance on signs.
From this point of view, the last vestiges of the "consoling" approach to treatment are to be found in the administration—often without any sort of adequate history being taken, or any sort of appropriate physical examination being made[41] -- of the morale-boosting and pleasing remedies, such as the "sugar pill", electuary or pharmaceutical syrup; all of which had no known pharmacodynamic action.
Those doctors who provided their patients with these sorts of morale-boosting therapies (which, whilst having no pharmacologically active ingredients, provided reassurance and comfort) did so either to reassure their patients whilst the vis medicatrix naturæ (i.e., "the healing power of nature") performed its normalizing task of restoring them to health, or to gratify their patients’ need for an active treatment.
Some statements about placebos in scientific articles are:
- Cooper (1823, p.259): "[When applying] the compound decoction of the sarsaparilla ... [in cases of] irritable ulcer, ... some think it placebo; others have a very high opinion of its efficacy ... [when it is used] after the use of mercury, it diminishes the irritability of the constitution, and soon soothes the system into peace" (emphasis added).
- Shapiro (1968, p.656): "[This use of the term "placebo" is a form of] positioning ... Introduction of the word placebo to describe a class of treatments not previously specified was an important development in the history of methodology and medicine."
- Handfield-Jones (1953): "some patients are so unintelligent, neurotic, or inadequate as to be incurable, and life is made easier for them by placebo".
- Platt (1947, p.307): "the frequency with which placebos are used varies inversely with the combined intellligence of the doctor and his patient".
- Steele (1891, pp 277–278)"To argue with a man, and especially with a woman, that there is little the matter with them might be thought injudicious, and to advise them to return at a more convenient occasion requires more time and resolution than writing out a prescription or administering a placebo."
- But Shapiro (1968, p.679): "If a placebo is prescribed by a physician because it is thought that it will help the patient, then it is a specific [remedy] and therefore not a placebo [at all]."
- An editorial in the British Medical Journal of 19 January 1952 (p.150): "But it is a fallacy to suppose that an inactive medicine can do no harm. If prescribed in a perfunctory way for a patient needing explanation and reassurance it may increase faith in his disease rather than in the remedy, and a doctor who gives a placebo in the wrong spirit may harm the patient."
- Pepper (1945, p.411): "There may be a time when during the carrying out of diagnostic tests it is undesirable to give potent medicine lest it interfere with the tests and yet the patient must be encouraged by treatment. ... there is a certain amount of skill in the choice and administration of a placebo. In the first place, it must be nothing more than what the name implies a medicine without any pharmacologic action whatever. Even a mild sedative is not a true placebo. Secondly, its name must be unknown to even the most inveterate patient who knows most drugs by name and is always quick to read the prescription. If the medicines named are familiar, the type of patient who needs a placebo will promptly exclaim that this or that drug had been tried and "had not helped me" or "had upset my stomach". It is well if the drug have a Latin and polysyllabic name; it is wise if it be prescribed with some assurance and emphasis for psychotherapeutic effect. The older physicians each had his favorite placeboic prescriptions—one chose Tincture of Condurango, another the Fluidextract [sic] of Cimicifuga nigra. Certainly this latter by its Latin name might be expected to have more supratentorial action than if one merely wrote for the Black Cohosh, and Condurango would be more efficacious than sugar of milk." Pepper's assertion that a placebo "must be nothing more than what the name implies"—namely that it must be "a medicine without any pharmacologic action whatever"—in order for it to be called a placebo, is most significant.
- Findley (1953), p.1826 & p.1824: "[If the placebo is not] used as an instrument of deception, but as a technique for cementing the emotional bond which must attach doctor to patient if any form of treatment is to be really successful… [it was] the most important weapon the physician has ... [specifically because] in proportion as this [doctor-patient] bond is firm, the [patient's] need for drugs will likely diminish."
- Leslie (1954, p.854): "Because medicine has been so concerned with its scientific growth too little attention has been paid to advancing the art of medicine, to which therapy with placebos belongs, and consequently knowledge of the use of placebos has not progressed significantly."
- Carruthers, Hoffman, Melmon & Nierenberg (2000, p.1268): "In clinical practice, where a majority of patient visits are for conditions that cannot be explained on a pathophysiologic basis of for which no specific treatment is available, it is essential that physicians understand the concepts and principles of placebos and placebo effects and, when appropriate, use them correctly".
## "Placebo" as a pejorative
Useless decoctions, drugs, treatments, remedies, and procedures are given the pejorative label placebo.
In the 14th century the English word "placebo" denoted a sycophant and a useless flatterer, but this usage became obsolete.
The second edition of Motherby’s (1785) New Medical Dictionary defines "placebo" as "a common place method or medicine" (not "a common place method of medicine" as often misquoted.)
Because this usage does not appear in English (or in any English, French, German, Italian, or Portuguese dictionary) before Motherby’s 1785 edition, Shapiro (1968, pp.656–657) is certain that this pejorative use of placebo was coined by Motherby. That Samuel Johnson's 1755 Dictionary of the English Language has no entry for placebo (or for placebo-singer or singer of placebo, see Placebo (at funeral)), strongly supports Shapiro's contention.
# Examples of effect
In 1938, Diehl, Baker and Cowan reported the results of a study that they had conducted over a two year period into the efficacy of injected vaccines in prevention of colds. Whilst their experimental group showed a significant reduction in the number of colds per person per year, the placebo control group reported the same magnitude of reduction as the vaccinated group.[42] This finding was significant, because they also found that their observed level of reduction in the number of colds per person per year matched that of other "uncontrolled studies"; which, given the demonstrated level of placebo responses, meant that "there is no evidence in this study… that vaccines reduce the complications of colds… in a cold-susceptiible group".[43]
By 1948, the term placebo effect was so widely established that an Egyptian physician could write to The Lancet, reporting that "The success achieved in 83% of cases cannot by any means be ascribed to suggestion or to a placebo effect."[44]
In 1949, Wolf conducted a series of investigations into the "measurable 'drug effects' that are not attributable to the chemical properties of the agents administered".[45] Wolf contrasting what he called drug effects with what he called placebo effects.
He noted the extent to which the "[observed] "placebo" actions depended for their force on the conviction of the patient that this or that effect would result".[46] He drew attention to the impressive frequency and magnitude of these placebo actions and placebo effects and how they could mimic, mask, potentiate, or prevent beneficial responses to the active drugs. He also stressed that all of these placebo actions and placebo effects, "which [modified] the pharmacologic action of drugs or [endowed] inert agents with potency" were associated with real and substantial physiological changes; and, therefore, they were not imaginary. His study also revealed that the action of a drug could be nullified or, even, reversed in the presence of emotional states such as anger, hostility or resentment.
He also observed that "these effects [were] at times more potent than the pharmacologic action customarily attributed to the [active] agent".[47] and spoke of the well-established understanding "that the mechanisms of the body are capable of reacting not only to direct physical and chemical stimulation but also to symbolic stimuli, words and events which have somehow acquired special meaning for the individual",[48] in the hope that, "in the future drugs will be assessed not only with reference to their pharmacologic action but also to the other [psychodynamic] forces at play and to the circumstances surrounding their administration".[49]
# Methodology of administration
Placebos are things like sugar pills, that look like real treatments but in fact have no physical effect. They are used to create "blind" trials in which the participants do not know whether they are getting the active treatment or not, so that physical effects can be measured independently of the participants' expectations. There are various effects of expectations, and blind trials control all of these together by making whatever expectations there are equal for all cases. Placebos are not the only possible technique for creating "blindness" (= unawareness of the treatment): to test the effectiveness of prayer by others, you just don't tell the participants who has and has not had prayers said for them. To test the effect of changing the frequency of fluorescent lights on headaches, you just change the light fittings at night in the absence of the office workers (this is a real case).
Related to this is the widespread opinion that placebo effects exist, where belief in the presence of a promising treatment (even though it is in fact an inert placebo) creates a real result e.g. recovery from disease. Placebos as a technique for "blinding" will remain important even if there is no placebo effect, but obviously it is in itself interesting to discover whether placebo effects exist, how common they are, and how large they are. After all, if they cure people then we probably want to employ them for that.
Claims that placebo effects are large and widespread go back to at least Beecher (1955). However Kienle and Kiene (1997) did a reanalysis of his reported work, and concluded his claims had no basis in his evidence. Beecher misinterpreted his data. Also, Beecher's methodology was very questionable. Then Hrobjartsson & Gotzsche (2001) did a meta-analysis or review of the evidence, and concluded that most of these claims have no basis in the clinical trials published to date. This opinion is widely spread in the placebo literature. The chief points of their skeptical argument are:
- Only trials that compare a group that gets no treatment with another group that gets a placebo can test the effect.
- Most claims are based on looking at the size of the improvement measured in placebo groups in trials comparing only placebo and experimental (active) treatments. This is misleading since (for instance) most diseases have a substantial clearup rate with no treatment: seeing improvements does not mean the placebo had an effect. (Put more technically, comparing with the baseline (pretest measure) is vulnerable to regression to the mean.)
Nevertheless, even they conclude that there is a real placebo effect for pain (not surprising since this is partly understood theoretically: Wall, 1999)); and for some other continuously-valued subjectively-assessed effects. A recent experimental demonstration was reported: Zubieta et al. (2005) "Endogenous Opiates and the Placebo Effect" The journal of neuroscience vol.25 no.34 p.7754–7762
This seems to show that the psychological cause (belief that the placebo treatment might be effective in reducing pain) causes opioid release in the brain, which then presumably operates in an analogous way to externally administered morphine.
A recent and more extensive review of the overall dispute is: M. Nimmo (2005) Placebo: Real, Imagined or Expected? A Critical Experimental Exploration Final year undergraduate Critical Review, Dept. of Psychology, University of Glasgow. PDF copy. | https://www.wikidoc.org/index.php/Non-specific_effect | |
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Peptides (from the Greek πεπτίδια, "small digestibles") are short polymers formed from the linking, in a defined order, of α-amino acids. The link between one amino acid residue and the next is known as an amide bond or a peptide bond.
Proteins are polypeptide molecules (or consist of multiple polypeptide subunits). The distinction is that peptides are short and polypeptides/proteins are long. There are several different conventions to determine these, all of which have flaws.
# Conventions
One convention is that those peptide chains that are short enough to be made synthetically from the constituent amino acids are called peptides rather than proteins. However, with the advent of better synthetic techniques, peptides as long as hundreds of amino acids can be made, including full proteins like ubiquitin. Native chemical ligation has given access to even longer proteins, so this convention seems to be outdated.
Another convention places an informal dividing line at approximately 50 amino acids in length (some people claim shorter lengths). However, this definition is somewhat arbitrary. Long peptides, such as the amyloid beta peptide linked to Alzheimer's disease, can be considered proteins; and small proteins, such as insulin, can be considered peptides.
# Peptide classes
Here are the major classes of peptides, according to how they are produced:
# Peptides in molecular biology
Peptides have received prominence in molecular biology in recent times for several reasons. The first and most important is that peptides allow the creation of peptide antibodies in animals without the need to purify the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein.
Another reason is that peptides have become instrumental in mass spectrometry, allowing the identification of proteins of interest based on peptide masses and sequence.
Peptides have recently been used in the study of protein structure and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur.
Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases.
# Well-known peptide families in humans
The peptide families in this section are all ribosomal peptides, usually with hormonal activity. All of these peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to exiting the cell. They are released into the bloodstream where they perform their signalling functions.
## The Tachykinin peptides
- Substance P
- Kassinin
- Neurokinin A
- Eledoisin
- Neurokinin B
## Vasoactive intestinal peptides
- VIP Vasoactive intestinal peptide
- PACAP Pituitary adenylate cyclase activating peptide
- PHI 27
- PHM 27
- GHRH 1-24 Growth hormone releasing hormone 1-24
- Glucagon
- Secretin
## Pancreatic polypeptide-related peptides
- NPY
- PYY Peptide YY
- APP Avian pancreatic polypeptide
- HPP Human pancreatic polypeptide
## Opioid peptides
- Proopiomelanocortin (POMC) Peptides
- The Enkephalin pentapeptides
- The Prodynorphin peptides
## Calcitonin peptides
- Calcitonin
- Amylin
- AGG01
# Notes on terminology
- A polypeptide is a single linear chain of amino acids.
- A protein are one or more polypeptides more than about 50 amino acids long.
- An oligopeptide or (simply) a peptide is a polypeptide less than 30-50 amino acids long.
- A dipeptide has two amino acids.
- A tripeptide has three amino acids.
- A pentapeptide has five amino acids.
- A nonapeptide has nine amino acids (e.g., oxytocin).
- A neuropeptide is a peptide that is active in association with neural tissue.
- A peptide hormone is a peptide that acts as a hormone. | Peptide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Peptides (from the Greek πεπτίδια, "small digestibles") are short polymers formed from the linking, in a defined order, of α-amino acids. The link between one amino acid residue and the next is known as an amide bond or a peptide bond.
Proteins are polypeptide molecules (or consist of multiple polypeptide subunits). The distinction is that peptides are short and polypeptides/proteins are long. There are several different conventions to determine these, all of which have flaws.
# Conventions
One convention is that those peptide chains that are short enough to be made synthetically from the constituent amino acids are called peptides rather than proteins. However, with the advent of better synthetic techniques, peptides as long as hundreds of amino acids can be made, including full proteins like ubiquitin. Native chemical ligation has given access to even longer proteins, so this convention seems to be outdated.
Another convention places an informal dividing line at approximately 50 amino acids in length (some people claim shorter lengths). However, this definition is somewhat arbitrary. Long peptides, such as the amyloid beta peptide linked to Alzheimer's disease, can be considered proteins; and small proteins, such as insulin, can be considered peptides.
# Peptide classes
Here are the major classes of peptides, according to how they are produced:
# Peptides in molecular biology
Peptides have received prominence in molecular biology in recent times for several reasons. The first and most important is that peptides allow the creation of peptide antibodies in animals without the need to purify the protein of interest.[11] This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein.
Another reason is that peptides have become instrumental in mass spectrometry, allowing the identification of proteins of interest based on peptide masses and sequence.
Peptides have recently been used in the study of protein structure and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur.
Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases.
# Well-known peptide families in humans
The peptide families in this section are all ribosomal peptides, usually with hormonal activity. All of these peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to exiting the cell. They are released into the bloodstream where they perform their signalling functions.
## The Tachykinin peptides
- Substance P
- Kassinin
- Neurokinin A
- Eledoisin
- Neurokinin B
## Vasoactive intestinal peptides
- VIP Vasoactive intestinal peptide
- PACAP Pituitary adenylate cyclase activating peptide
- PHI 27
- PHM 27
- GHRH 1-24 Growth hormone releasing hormone 1-24
- Glucagon
- Secretin
## Pancreatic polypeptide-related peptides
- NPY
- PYY Peptide YY
- APP Avian pancreatic polypeptide
- HPP Human pancreatic polypeptide
## Opioid peptides
- Proopiomelanocortin (POMC) Peptides
- The Enkephalin pentapeptides
- The Prodynorphin peptides
## Calcitonin peptides
- Calcitonin
- Amylin
- AGG01
# Notes on terminology
- A polypeptide is a single linear chain of amino acids.
- A protein are one or more polypeptides more than about 50 amino acids long.
- An oligopeptide or (simply) a peptide is a polypeptide less than 30-50 amino acids long.
- A dipeptide has two amino acids.
- A tripeptide has three amino acids.
- A pentapeptide has five amino acids.
- A nonapeptide has nine amino acids (e.g., oxytocin).
- A neuropeptide is a peptide that is active in association with neural tissue.
- A peptide hormone is a peptide that acts as a hormone. | https://www.wikidoc.org/index.php/Nonapeptide | |
fc6b788c4ca8e688fee99f51590cf27449b07b92 | wikidoc | Scabies | Scabies
Synonyms and keywords: Norwegian scabies
# Overview
Scabies is a skin infection caused by Sarcoptes scabiei and the mite is transmitted mostly by direct skin-to-skin contact. Scabies can be classified into 2 major types depending on the resultant skin lesions into typical scabies infestation and crusted (or Norwegian scabies). Crusted scabies is usually associated with an immunocompromised status. The characteristic symptoms of scabies is that of intense itching, which is worse at night and erythema of the skin. Examination reveals skin lesions of various sizes in certain areas of predilection, which include the webs of fingers and toes and wrists. With appropriate antimicrobial therapy, scabies has an excellent prognosis. Treatment must be initiated for patients and individuals with close contact with the patient, even if they are asymptomatic.
# Historical Perspective
- In 1687, Giovan Cosimo Bonomo, an Italian physician, described the relationship between mites infestation and the resultant skin lesions.
- Cases of scabies have been described in literature as early as 1853.
- In the early days, the use of sulfur-containing products, whether in the form of baths, vapors or ointments was believed to be the treatment of choice for scabies.
# Classification
Scabies can be divided into 2 major types depending on the resultant skin lesions:
# Pathophysiology
## Pathogenesis
### Mode of Transmission
The most common mode of transmission of scabies is through direct skin-to-skin contact. However other methods of transmission include:
- Sexual transmission, especially among men who have sex with men
- Fomites and shared clothing are a rare source of transmission of scabies; however, cases are more likely to occur with crusted scabies, due to the higher burden of mites
- Cross infectivity from other mammals: this is a rare mode of transmission, however, cases of cross infectivity of humans from companion dogs were reported.
### Mite Lifecycle and Pathogenesis
The following summarizes the lifecycle of the mite and the pathophysiology behind scabies infection:
- Away from the host, mites are viable for a period of 24-36 hours at a temperature of 21 C.
- Once the female mite comes in contact with human skin, it digs a small tunnel (i.e.: burrow) at a rate of 0.5-5.0 mm per day through the layers of the epidermis.
- A male mite searches for an unfertilized female, which lays 2-4 eggs per day and larvae hatches 2-4 days later. Larvae develop into adult mites 10-14 days later.
- The clinical presentation of intense itching, redness of the skin and the multiple skin lesions are due to a delayed type hypersensitivity reaction by the host immune system.
## Microscopic Pathology
The histopathology of scabies consists of mites being surrounded by an inflammatory infiltrate of eosinophils, lymphocytes and histiocytes.
## Associated Conditions
Crusted scabies may be associated with the following medical conditions:
- Down Syndrome
- Underlying immunosuppression, such as patients with:
Diabetes mellitus
HIV
HTLV-1
Leukemia
- Diabetes mellitus
- HIV
- HTLV-1
- Leukemia
# Causes
The cause of scabies infection is Sarcoptes scabiei. For more information about the causative organism, click here.
# Differentiating Scabies from Other Diseases
Scabies must be differentiated from the following pathologies:
# Epidemiology and Demographics
## Epidemiology
### Prevalence
The following data exists on the prevalence of scabies around the world:
- The prevalence of scabies worldwide varies greatly; it ranges from 200 to 71,400 per 100,00 cases.
- All regions had a prevalence of more than 10,000 per 100,000 cases, except in Europe and the Middle East.
- It is estimated that there are 300 million cases of scabies worldwide.
## Demographics
### Age
Scabies is more common in children and adolescents than adults.
### Region
- The Pacific and Latin America have the highest prevalence of scabies worldwide, while it is the lowest in Europe and the Middle East.
# Risk Factors
The following are believed to be risk factors for scabies:
- Living in high-risk areas, such as Sub-Saharan Africa and indigenous communities in Australia and New Zealand
- Living in crowded areas
- Homeless or displaced children
- Poor hygiene: the role of poor hygiene in the development of scabies is uncertain, as mites burrowed under the skin remain alive even after daily hot baths and are usually resistant to water and soap
- Immunocompromised individuals, such as the elderly, malnourished and those with HIV, DM are at risk of developing Norwegian Scabies, which is the severe form
# Screening
There are no screening recommendations for scabies.
# Natural History, Complications and Prognosis
## Natural History
If left untreated, scabies infection can lead to secondary bacterial infection of the skin and underlying soft tissue. These can have severe complications, such as sepsis, post-streptococcal glomerulonephritis and rheumatic heart disease, especially in an immunocompromised host.
## Complications
Major complications of scabies include:
- Secondary bacterial infection of the skin and soft tissue, caused mainly by S. aureus and S. pyogenes, which include:
Impetigo
Skin abscess
Cellulitis
Necrotizing fasciitis
- Impetigo
- Skin abscess
- Cellulitis
- Necrotizing fasciitis
- Secondary bacterial infection of the skin and soft tissue can progress to life-threatening complications such as:
Septicemia
Post-streptococcal glomerulonephritis
Renal failure
Rheumatic heart disease
- Septicemia
- Post-streptococcal glomerulonephritis
- Renal failure
- Rheumatic heart disease
## Prognosis
The prognosis of scabies is usually excellent. With prompt treatment with antimicrobial therapy, the infection and itching usually resolves within a matter of weeks.
# Diagnosis
## History and Symptoms
- In suspected cases of scabies, make sure to enquire about the following:
History of exposure to a known case of scabies or coming in close contact with patients with a similar complaint (mainly itching)
In the case of children, ask about daycare attendance
History of hospitalization
Recent travel history
- History of exposure to a known case of scabies or coming in close contact with patients with a similar complaint (mainly itching)
- In the case of children, ask about daycare attendance
- History of hospitalization
- Recent travel history
- The main symptoms in patients with scabies include:
Intense itching, which is worse at night
Skin lesions, which are typically red and of few millimeters in size, found mostly on finger webs, wrists, elbows, axillae, buttocks and groin
- Intense itching, which is worse at night
- Skin lesions, which are typically red and of few millimeters in size, found mostly on finger webs, wrists, elbows, axillae, buttocks and groin
## Physical Examination
In patients with scabies, skin should be carefully examined to look for:
- Burrows: are the tunnels which the female mite penetrates into the skin. Initially, they are not clinically visible and can only be seen several days later, when the host immune system forms a local reaction around the tunnel. Burrows are characterized by short, wavy lines.
- Papules: they are usually small and erythematous. The distribution of the papules is variable; they can be sparse or very close to each other. Over the course of the infection, papules can transform into vesicles and/or bullae. Characteristic distribution of scabies usually involves the web spaces of fingers and toes, the wrists and areolae of breasts in females and penis in males. The back is usually spared, while face and neck involvement are usually only seen in infants and children.
- Excoriations: skin excoriations are commonly seen in patients with scabies, due to the intense itching associated with the infection.
### Skin
- url = >
- url = >
- url = >
- url = >
- url = >
- Scabies (common location in ventral wrist)
- url = >
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- url = >
- url = >
- url = >
- url = >
- url = >
- url = >
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- Norwegian scabies. / Adapted from Dermatology Atlas.
- url = >
- url = >
- url = >
- url = >
- url = >
- url = >
## Laboratory Findings
- Serologic testing for Sarcoptes scabiei has a very high sensitivity and specificity.
- Peripheral IgE levels are elevated in patients with Norwegian Scabies.
## Other Diagnostic Studies
### Light Microscopy
The gold standard for diagnosis of scabies infection is visualization of the ova, feces or the mite itself on light microscopy.
### Skin Biopsy
Skin biopsy is another means for diagnosing scabies. Visualization of the mites in the stratum corneum layer of the skin confirms the diagnosis.
# Treatment
## Medical Therapy
Medical therapy in patients with scabies consists of antimicrobial therapy, mainly either with topical permethrin or oral ivermectin. Patients may experience worsening pruritus and erythema early during the administration of antimicrobial therapy. However, the parasite is gradually eliminated during the body's natural shedding process. The following summarizes the preferred antimicrobial regimens in the treatment of scabies:
- Antimicrobial therapy
- 1. Adult
- Preferred regimen (1): Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours;
- Preferred regimen (2): Ivermectin 200 ug/kg given orally, 4 times daily and repeated in 2 weeks as it has limited ovicidal activity;
- Preferred regimen (3): Ivermectin 1% lotion - applied to all areas of the body from the neck down and washed off after 8–14 hours; repeat treatment in 1 week if symptoms persist;
- Alternative regimen: Lindane (1%) 1 oz of lotion or 30 g of cream applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
- Lindane is an alternative choice because of its toxicity. Lindane is not recommended for pregnant and breastfeeding women, children aged <10 years, and persons with extensive dermatitis. Seizures have occurred when lindane was applied after a bath or used by patients who had extensive dermatitis. Aplastic anemia after lindane use also has been reported. Resistance has also been reported.
- Note: Patients may experience worsening pruritus and erythema early during the administration of antimicrobial therapy
- 2. Infants and young children
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours;
- Note: Infants and young children aged< 10 years should not be treated with lindane.
- 3. Crusted Scabies
- Preferred regimen: (Topical scabicide topical Benzyl benzoate 25% OR topical Permethrin 5% cream (full-body application to be repeated daily for 7 days then twice weekly until discharge or cure) AND treatment with Ivermectin 200 ug/kg PO on days 1,2,8,9, and 15. Additional Ivermectin treatment on days 22 and 29 might be required for severe cases;
- 4.Pregnant or Lactating Women
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours.
## Primary Prevention
One of the most important means of preventing scabies is to encourage good hygiene and advocate healthy living conditions away from crowded conditions.
## Secondary Prevention
Once a patient has been diagnosed with scabies, it is empirical to begin treatment with the appropriate antimicrobial therapy to eradicate the infection and prevent re-infection. However, the following measures must also be followed:
- Treatment of individuals who come in close contact with the patient, even if they are asymptomatic
- Fomites, such as clothes, towels and bed linens, must be machine washed and dried at a high temperature (60 C)
- Insecticide may be used for items that cannot be washed | Scabies
Template:DiseaseDisorder infobox
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Dima Nimri, M.D. [3]
Synonyms and keywords: Norwegian scabies
# Overview
Scabies is a skin infection caused by Sarcoptes scabiei and the mite is transmitted mostly by direct skin-to-skin contact. Scabies can be classified into 2 major types depending on the resultant skin lesions into typical scabies infestation and crusted (or Norwegian scabies). Crusted scabies is usually associated with an immunocompromised status. The characteristic symptoms of scabies is that of intense itching, which is worse at night and erythema of the skin. Examination reveals skin lesions of various sizes in certain areas of predilection, which include the webs of fingers and toes and wrists. With appropriate antimicrobial therapy, scabies has an excellent prognosis. Treatment must be initiated for patients and individuals with close contact with the patient, even if they are asymptomatic.
# Historical Perspective
- In 1687, Giovan Cosimo Bonomo, an Italian physician, described the relationship between mites infestation and the resultant skin lesions.[1][2]
- Cases of scabies have been described in literature as early as 1853.[3]
- In the early days, the use of sulfur-containing products, whether in the form of baths, vapors or ointments was believed to be the treatment of choice for scabies.[4]
# Classification
Scabies can be divided into 2 major types depending on the resultant skin lesions:[1][5][6][7][8][9][10][11]
# Pathophysiology
## Pathogenesis
### Mode of Transmission
The most common mode of transmission of scabies is through direct skin-to-skin contact. However other methods of transmission include:[1][12][13][14][15][16]
- Sexual transmission, especially among men who have sex with men
- Fomites and shared clothing are a rare source of transmission of scabies; however, cases are more likely to occur with crusted scabies, due to the higher burden of mites
- Cross infectivity from other mammals: this is a rare mode of transmission, however, cases of cross infectivity of humans from companion dogs were reported.
### Mite Lifecycle and Pathogenesis
The following summarizes the lifecycle of the mite and the pathophysiology behind scabies infection:[17][1][13][18]
- Away from the host, mites are viable for a period of 24-36 hours at a temperature of 21 C.
- Once the female mite comes in contact with human skin, it digs a small tunnel (i.e.: burrow) at a rate of 0.5-5.0 mm per day through the layers of the epidermis.
- A male mite searches for an unfertilized female, which lays 2-4 eggs per day and larvae hatches 2-4 days later. Larvae develop into adult mites 10-14 days later.
- The clinical presentation of intense itching, redness of the skin and the multiple skin lesions are due to a delayed type hypersensitivity reaction by the host immune system.
## Microscopic Pathology
The histopathology of scabies consists of mites being surrounded by an inflammatory infiltrate of eosinophils, lymphocytes and histiocytes.[1][19][20]
## Associated Conditions
Crusted scabies may be associated with the following medical conditions:[1][5][6][7][8][9][10][11]
- Down Syndrome
- Underlying immunosuppression, such as patients with:
Diabetes mellitus
HIV
HTLV-1
Leukemia
- Diabetes mellitus
- HIV
- HTLV-1
- Leukemia
# Causes
The cause of scabies infection is Sarcoptes scabiei.[17] For more information about the causative organism, click here.
# Differentiating Scabies from Other Diseases
Scabies must be differentiated from the following pathologies:[1][21][22][23][24][25][26][27]
# Epidemiology and Demographics
## Epidemiology
### Prevalence
The following data exists on the prevalence of scabies around the world:[17][12]
- The prevalence of scabies worldwide varies greatly; it ranges from 200 to 71,400 per 100,00 cases.
- All regions had a prevalence of more than 10,000 per 100,000 cases, except in Europe and the Middle East.
- It is estimated that there are 300 million cases of scabies worldwide.
## Demographics
### Age
Scabies is more common in children and adolescents than adults.[28][29][30][31]
### Region
- The Pacific and Latin America have the highest prevalence of scabies worldwide, while it is the lowest in Europe and the Middle East.[17]
# Risk Factors
The following are believed to be risk factors for scabies:[17][1][32][33][34][35][36][37][28]
- Living in high-risk areas, such as Sub-Saharan Africa and indigenous communities in Australia and New Zealand
- Living in crowded areas
- Homeless or displaced children
- Poor hygiene: the role of poor hygiene in the development of scabies is uncertain, as mites burrowed under the skin remain alive even after daily hot baths and are usually resistant to water and soap
- Immunocompromised individuals, such as the elderly, malnourished and those with HIV, DM are at risk of developing Norwegian Scabies, which is the severe form
# Screening
There are no screening recommendations for scabies.[38]
# Natural History, Complications and Prognosis
## Natural History
If left untreated, scabies infection can lead to secondary bacterial infection of the skin and underlying soft tissue. These can have severe complications, such as sepsis, post-streptococcal glomerulonephritis and rheumatic heart disease, especially in an immunocompromised host.[1][17][39]
## Complications
Major complications of scabies include:[17][1][39]
- Secondary bacterial infection of the skin and soft tissue, caused mainly by S. aureus and S. pyogenes, which include:
Impetigo
Skin abscess
Cellulitis
Necrotizing fasciitis
- Impetigo
- Skin abscess
- Cellulitis
- Necrotizing fasciitis
- Secondary bacterial infection of the skin and soft tissue can progress to life-threatening complications such as:
Septicemia
Post-streptococcal glomerulonephritis
Renal failure
Rheumatic heart disease
- Septicemia
- Post-streptococcal glomerulonephritis
- Renal failure
- Rheumatic heart disease
## Prognosis
The prognosis of scabies is usually excellent. With prompt treatment with antimicrobial therapy, the infection and itching usually resolves within a matter of weeks.[12]
# Diagnosis
## History and Symptoms
- In suspected cases of scabies, make sure to enquire about the following:[28]
History of exposure to a known case of scabies or coming in close contact with patients with a similar complaint (mainly itching)
In the case of children, ask about daycare attendance
History of hospitalization
Recent travel history
- History of exposure to a known case of scabies or coming in close contact with patients with a similar complaint (mainly itching)
- In the case of children, ask about daycare attendance
- History of hospitalization
- Recent travel history
- The main symptoms in patients with scabies include:[1][17][30][12]
Intense itching, which is worse at night
Skin lesions, which are typically red and of few millimeters in size, found mostly on finger webs, wrists, elbows, axillae, buttocks and groin
- Intense itching, which is worse at night
- Skin lesions, which are typically red and of few millimeters in size, found mostly on finger webs, wrists, elbows, axillae, buttocks and groin
## Physical Examination
In patients with scabies, skin should be carefully examined to look for:[1][17][40][41][37][42][43][28]
- Burrows: are the tunnels which the female mite penetrates into the skin. Initially, they are not clinically visible and can only be seen several days later, when the host immune system forms a local reaction around the tunnel. Burrows are characterized by short, wavy lines.
- Papules: they are usually small and erythematous. The distribution of the papules is variable; they can be sparse or very close to each other. Over the course of the infection, papules can transform into vesicles and/or bullae. Characteristic distribution of scabies usually involves the web spaces of fingers and toes, the wrists and areolae of breasts in females and penis in males. The back is usually spared, while face and neck involvement are usually only seen in infants and children.
- Excoriations: skin excoriations are commonly seen in patients with scabies, due to the intense itching associated with the infection.
### Skin
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=415>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- Scabies (common location in ventral wrist) [44]
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=415>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=415>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- Norwegian scabies. http://www.atlasdermatologico.com.br/ Adapted from Dermatology Atlas.[45]
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=414>
## Laboratory Findings
- Serologic testing for Sarcoptes scabiei has a very high sensitivity and specificity.[28][46]
- Peripheral IgE levels are elevated in patients with Norwegian Scabies.[19][20]
## Other Diagnostic Studies
### Light Microscopy
The gold standard for diagnosis of scabies infection is visualization of the ova, feces or the mite itself on light microscopy.[28][47][48]
### Skin Biopsy
Skin biopsy is another means for diagnosing scabies. Visualization of the mites in the stratum corneum layer of the skin confirms the diagnosis.[28]
# Treatment
## Medical Therapy
Medical therapy in patients with scabies consists of antimicrobial therapy, mainly either with topical permethrin or oral ivermectin. Patients may experience worsening pruritus and erythema early during the administration of antimicrobial therapy. However, the parasite is gradually eliminated during the body's natural shedding process. The following summarizes the preferred antimicrobial regimens in the treatment of scabies:[49][28][47][50][1][51][52][53]
- Antimicrobial therapy
- 1. Adult
- Preferred regimen (1): Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours;
- Preferred regimen (2): Ivermectin 200 ug/kg given orally, 4 times daily and repeated in 2 weeks as it has limited ovicidal activity;
- Preferred regimen (3): Ivermectin 1% lotion - applied to all areas of the body from the neck down and washed off after 8–14 hours; repeat treatment in 1 week if symptoms persist;
- Alternative regimen: Lindane (1%) 1 oz of lotion or 30 g of cream applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
- Lindane is an alternative choice because of its toxicity. Lindane is not recommended for pregnant and breastfeeding women, children aged <10 years, and persons with extensive dermatitis. Seizures have occurred when lindane was applied after a bath or used by patients who had extensive dermatitis. Aplastic anemia after lindane use also has been reported. Resistance has also been reported.
- Note: Patients may experience worsening pruritus and erythema early during the administration of antimicrobial therapy
- 2. Infants and young children
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours;
- Note: Infants and young children aged< 10 years should not be treated with lindane.
- 3. Crusted Scabies
- Preferred regimen: (Topical scabicide topical Benzyl benzoate 25% OR topical Permethrin 5% cream (full-body application to be repeated daily for 7 days then twice weekly until discharge or cure) AND treatment with Ivermectin 200 ug/kg PO on days 1,2,8,9, and 15. Additional Ivermectin treatment on days 22 and 29 might be required for severe cases;
- 4.Pregnant or Lactating Women
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours.
## Primary Prevention
One of the most important means of preventing scabies is to encourage good hygiene and advocate healthy living conditions away from crowded conditions.[17]
## Secondary Prevention
Once a patient has been diagnosed with scabies, it is empirical to begin treatment with the appropriate antimicrobial therapy to eradicate the infection and prevent re-infection. However, the following measures must also be followed:[12][54]
- Treatment of individuals who come in close contact with the patient, even if they are asymptomatic
- Fomites, such as clothes, towels and bed linens, must be machine washed and dried at a high temperature (60 C)
- Insecticide may be used for items that cannot be washed | https://www.wikidoc.org/index.php/Norwegian_scabies | |
789ea36bad78274395a948570527f2be18e68503 | wikidoc | Notch 1 | Notch 1
Notch homolog 1, translocation-associated (Drosophila), also known as NOTCH1, is a human gene encoding a single-pass transmembrane receptor.
# Function
This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in humans, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play multiple roles during development.
A deficiency can be associated with bicuspid aortic valve.
There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia. Notch 1, when activated before birth, induces radial glia differentiation, but postnatally induces the differentiation into astrocytes. One study shows that Notch-1 cascade is activated by Reelin in an unidentified way. Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.
# Interactions
NOTCH1 has been shown to interact with:
- GSK3B,
- Lck,
- MAML1,
- Mothers against decapentaplegic homolog 3
- NFKB1,
- NOV,
- RBPJ,
- SNW1,
- Ubiquitin C, and
- YY1. | Notch 1
Notch homolog 1, translocation-associated (Drosophila), also known as NOTCH1, is a human gene encoding a single-pass transmembrane receptor.
# Function
This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in humans, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play multiple roles during development.[1]
A deficiency can be associated with bicuspid aortic valve.[2]
There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia.[3] Notch 1, when activated before birth, induces radial glia differentiation,[4] but postnatally induces the differentiation into astrocytes.[5] One study shows that Notch-1 cascade is activated by Reelin in an unidentified way.[6] Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.[7]
# Interactions
NOTCH1 has been shown to interact with:
- GSK3B,[8]
- Lck,[9]
- MAML1,[10][11]
- Mothers against decapentaplegic homolog 3[12]
- NFKB1,[13][14]
- NOV,[15]
- RBPJ,[16][17]
- SNW1,[18][19]
- Ubiquitin C,[20] and
- YY1.[21] | https://www.wikidoc.org/index.php/Notch_1 | |
73b31378ca2d58ddceac7e25e474ca62b1ee7231 | wikidoc | Notch 2 | Notch 2
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.
NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome.
# Function
Notch 2 is a member of the notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development.
Mutations within the last coding exon of Notch2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of the Hajdu-Cheney syndrome.
# Interactions
NOTCH2 has been shown to interact with:
- Delta-like 1
- GSK3B,
- JAG1, and
- JAG2. | Notch 2
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.[1]
NOTCH2 is associated with Alagille syndrome[2] and Hajdu–Cheney syndrome.[3]
# Function
Notch 2 is a member of the notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development.[4]
Mutations within the last coding exon of Notch2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of the Hajdu-Cheney syndrome.[5][6][7]
# Interactions
NOTCH2 has been shown to interact with:
- Delta-like 1[8][9][10]
- GSK3B,[11]
- JAG1,[8][9][12] and
- JAG2.[9] | https://www.wikidoc.org/index.php/Notch_2 | |
3828d521688a1caf31cbaf116bd3e79b7332ee98 | wikidoc | OSTbeta | OSTbeta
Organic solute transporter beta, also known as OST-beta, is a protein which in humans is encoded by the OSTB gene.
# Function
OST-beta together with OST-alpha is able to transport estrone sulfate, taurocholate, digoxin, and prostaglandin E2 across cell membranes. The Ost-alpha / Ost-beta heterodimer, but not the individual subunits, stimulates sodium-independent bile acid uptake. The heterodimer furthermore is essential for intestinal bile acid transport.
OST-alpha and OST-beta have high expression in the testis, colon, liver, small intestine, kidney, ovary, and adrenal gland. | OSTbeta
Organic solute transporter beta, also known as OST-beta, is a protein which in humans is encoded by the OSTB gene.[1][2]
# Function
OST-beta together with OST-alpha is able to transport estrone sulfate, taurocholate, digoxin, and prostaglandin E2 across cell membranes.[2][3] The Ost-alpha / Ost-beta heterodimer, but not the individual subunits, stimulates sodium-independent bile acid uptake.[3] The heterodimer furthermore is essential for intestinal bile acid transport.[4]
OST-alpha and OST-beta have high expression in the testis, colon, liver, small intestine, kidney, ovary, and adrenal gland.[2] | https://www.wikidoc.org/index.php/OSTbeta | |
6d3b9224ca8dace25b82ae39244264e7bda62a0b | wikidoc | Oatmeal | Oatmeal
In the United States and Canada, oatmeal means any crushed oats, rolled oats, or cut oats used in recipes such as oatmeal cookies. Oatmeal is a product made by processing oats. Oatmeal is coarsely ground unsifted oats. Rolled oats and steel-cut oats are also called oatmeal. The porridge made from this is also called oatmeal or oatmeal cereal. However in other parts of the English-speaking world, oatmeal means coarsely ground groats (i.e. oat-meal, cf. cornmeal, peasemeal, etc.). The groats are coarsely ground to make oatmeal, or cut into small pieces to make steel-cut oats, or steamed and rolled to make rolled oats. The quick-cooking rolled oats are cut into small pieces before being steamed and rolled. Oatmeal porridge contains more B vitamins and calories than other kinds of porridges. Oatmeal is used in some alcoholic drinks, cosmetics, soaps, external medical treatments, and is sometimes an added flavour in canned animal products. It is also used as a thickener in some brands of canned chili con carne.
# Breakfast cereal
There has been increasing interest in oatmeal in recent years due to its beneficial health effects. Studies have shown that daily consumption of a bowl of oatmeal can lower blood cholesterol. After reports found that oats can help lower cholesterol, an "oat bran craze" swept the U.S. in the late 1980s, peaking in 1989. The food fad was short-lived and faded by the early 1990s. The popularity of oatmeal and other oat products again increased after the January 1997 decision by the Food and Drug Administration that food with a lot of oat bran or rolled oats can carry a label claiming it may reduce the risk of heart disease, when combined with a low-fat diet. This is because of the beta-glucan in the oats. Rolled oats have also long been a staple of many athletes' diets, especially weight trainers', given oatmeal's high content of complex carbohydrates and fiber which encourage slow digestion and stable blood-glucose levels. Despite these developments, according to the New York Times, Harry Balzar of the NPD Group stated that "the proportion of Americans who eat oatmeal for breakfast has not changed in 20 years;" "one in five Americans eat oatmeal."
Some of the items added to oatmeal porridge to enhance its flavour include salt, white sugar, brown sugar, cinnamon, honey, molasses, maple syrup, butter, milk, cream, strawberries, blueberries, apples, peaches, mangos, bananas, raisins, dried cherries and dried cranberries. Many times nuts are also added including pecans and walnuts. Peanut butter is also a tasty addition.
# Oatmeal in Scotland
In Scotland, oatmeal is created by grinding oats into a coarse powder. Various grades are available depending on the thoroughness of the grinding, including Coarse, Pin(head) and Fine oatmeal. The main uses are:
- as an ingredient in baking
- in the manufacture of bannocks or oatcakes
- as a stuffing for poultry
- as a coating for Caboc cheese
- as the main ingredient of the Scottish dish, skirlie, or its chip-shop counterpart, the deep-fried thickly-battered mealy pudding
- mixed with sheep's blood, salt, and pepper to make Highland black pudding
- mixed with fat, water, onions and seasoning, and boiled in a sheep's intestine to make "marag geal"' Outer Hebridean white pudding, served sliced with fried eggs at breakfast.
- Traditional porridge (or "porage")
- Brose: a thick mixture made with uncooked oatmeal and butter or cream; eaten like porridge but much more filling.
- Rolled oats, crushed oats, and other "instant" variations are often used for this purpose nowadays, since they are quicker to prepare.
- Gruel, made by mixing oatmeal with cold water which is then strained and heated for the benefit of infants and invalids.
Oatmeal has a long history in Scottish society because oats are better suited than wheat to the short, wet growing season. Hence it became the staple grain of that country. Ancient Scottish Universities had an holiday called Meal Monday, to permit students to return to their farms and collect more oats for food. Samuel Johnson referred, disparagingly, to this in his dictionary definition for oats:
To which his biographer, James Boswell (a Scot), is said to have retorted
A common alternative method of cooking oatmeal in Scotland is to soak it overnight in salted water and cook on a low heat in the morning for a few minutes until the mixture thickens.
# Oatmeal in Vermont
In the U.S. state of Vermont oatmeal making has a long tradition originating in farm families. While there are variations, most begin with heavy steel cut oats. The oats are soaked overnight in cold water, salt and maple syrup. Early the next morning, before beginning farm chores the cook will add ground nutmeg, ground cinnamon and sometimes ground ginger. The pot is placed over heat and cooks for upwards of 90 minutes, being served after the chores with cream, milk, or butter. As most contemporary Vermonters no longer have farm chores, the recipe is simplified to a briefer 10 to 30 minute cooking at a higher heat. Vermont leads the U.S. in per capita consumption of cooked oatmeal cereal. | Oatmeal
In the United States and Canada, oatmeal means any crushed oats, rolled oats, or cut oats used in recipes such as oatmeal cookies. Oatmeal is a product made by processing oats. Oatmeal is coarsely ground unsifted oats. Rolled oats and steel-cut oats are also called oatmeal. The porridge made from this is also called oatmeal or oatmeal cereal. However in other parts of the English-speaking world, oatmeal means coarsely ground groats (i.e. oat-meal, cf. cornmeal, peasemeal, etc.). The groats are coarsely ground to make oatmeal, or cut into small pieces to make steel-cut oats, or steamed and rolled to make rolled oats. The quick-cooking rolled oats are cut into small pieces before being steamed and rolled. Oatmeal porridge contains more B vitamins and calories than other kinds of porridges.[1] Oatmeal is used in some alcoholic drinks, cosmetics, soaps, external medical treatments, and is sometimes an added flavour in canned animal products. It is also used as a thickener in some brands of canned chili con carne.
# Breakfast cereal
There has been increasing interest in oatmeal in recent years due to its beneficial health effects. Studies have shown that daily consumption of a bowl of oatmeal can lower blood cholesterol. After reports found that oats can help lower cholesterol, an "oat bran craze" swept the U.S. in the late 1980s, peaking in 1989. The food fad was short-lived and faded by the early 1990s. The popularity of oatmeal and other oat products again increased after the January 1997 decision by the Food and Drug Administration that food with a lot of oat bran or rolled oats can carry a label claiming it may reduce the risk of heart disease, when combined with a low-fat diet. This is because of the beta-glucan in the oats. Rolled oats have also long been a staple of many athletes' diets, especially weight trainers', given oatmeal's high content of complex carbohydrates and fiber which encourage slow digestion and stable blood-glucose levels. Despite these developments, according to the New York Times, Harry Balzar of the NPD Group stated that "the proportion of Americans who eat oatmeal for breakfast has not changed in 20 years;" "one in five Americans eat oatmeal."
Some of the items added to oatmeal porridge to enhance its flavour include salt, white sugar, brown sugar, cinnamon, honey, molasses, maple syrup, butter, milk, cream, strawberries, blueberries, apples, peaches, mangos, bananas, raisins, dried cherries and dried cranberries. Many times nuts are also added including pecans and walnuts. Peanut butter is also a tasty addition.
# Oatmeal in Scotland
In Scotland, oatmeal is created by grinding oats into a coarse powder. Various grades are available depending on the thoroughness of the grinding, including Coarse, Pin(head) and Fine oatmeal. The main uses are:
- as an ingredient in baking
- in the manufacture of bannocks or oatcakes
- as a stuffing for poultry
- as a coating for Caboc cheese
- as the main ingredient of the Scottish dish, skirlie, or its chip-shop counterpart, the deep-fried thickly-battered mealy pudding
- mixed with sheep's blood, salt, and pepper to make Highland black pudding
- mixed with fat, water, onions and seasoning, and boiled in a sheep's intestine to make "marag geal"' Outer Hebridean white pudding, served sliced with fried eggs at breakfast.
- Traditional porridge (or "porage")
- Brose: a thick mixture made with uncooked oatmeal and butter or cream; eaten like porridge but much more filling.
- Rolled oats, crushed oats, and other "instant" variations are often used for this purpose nowadays, since they are quicker to prepare.
- Gruel, made by mixing oatmeal with cold water which is then strained and heated for the benefit of infants and invalids.
Oatmeal has a long history in Scottish society because oats are better suited than wheat to the short, wet growing season. Hence it became the staple grain of that country. Ancient Scottish Universities had an holiday called Meal Monday, to permit students to return to their farms and collect more oats for food. Samuel Johnson referred, disparagingly, to this in his dictionary definition for oats:
To which his biographer, James Boswell (a Scot), is said to have retorted
A common alternative method of cooking oatmeal in Scotland is to soak it overnight in salted water and cook on a low heat in the morning for a few minutes until the mixture thickens.
# Oatmeal in Vermont
In the U.S. state of Vermont oatmeal making has a long tradition originating in farm families. While there are variations, most begin with heavy steel cut oats. The oats are soaked overnight in cold water, salt and maple syrup. Early the next morning, before beginning farm chores the cook will add ground nutmeg, ground cinnamon and sometimes ground ginger. The pot is placed over heat and cooks for upwards of 90 minutes, being served after the chores with cream, milk, or butter. As most contemporary Vermonters no longer have farm chores, the recipe is simplified to a briefer 10 to 30 minute cooking at a higher heat. Vermont leads the U.S. in per capita consumption of cooked oatmeal cereal.[citation needed] | https://www.wikidoc.org/index.php/Oatmeal | |
3c8f8d0d756d927617b95466f5ce092d345bdea6 | wikidoc | Octanol | Octanol
Octanol is a straight chain fatty alcohol with eight carbon atoms and the molecular formula CH3(CH2)7OH. Although the term octanol usually refers exclusively to the primary alcohol 1-octanol, there are other less common isomers of octanol such as the secondary alcohols 2-octanol, 3-octanol and 4-octanol.
Octanol occurs naturally in the form of esters in some essential oils. The primary use of octanol is in the manufacture of various esters (both synthetic and naturally occurring), such as octyl acetate, which are used in perfumery and flavors. Other uses include experimental medical applications utilizing octanol to control certain types of involuntary tremors.
# Water/ octanol partitioning
Octanol and water are immiscible. The distribution of a compound between water and octanol is used to calculate the partition coefficient 'P' of that molecule (often expressed as its logarithm to the base 10, log P). Water/ octanol partitioning is a good approximation of the partitioning between the cytosol and lipid membranes of living systems.
Many dermal absorption models consider the stratum corneum/ water partition coefficient to be well approximated by a function of the water/ octanol partition coefficient of the form
Where a and b are constants,K_{sc/w} is the stratum corneum/ water partition coefficient, andK_{o/w} is the water/ octanol partition coefficient. The values of a and b vary between papers, but Cleek & Bunge
have reported the values a=0, b=0.74. | Octanol
Template:Chembox new
Octanol is a straight chain fatty alcohol with eight carbon atoms and the molecular formula CH3(CH2)7OH. Although the term octanol usually refers exclusively to the primary alcohol 1-octanol, there are other less common isomers of octanol such as the secondary alcohols 2-octanol, 3-octanol and 4-octanol.
Octanol occurs naturally in the form of esters in some essential oils. The primary use of octanol is in the manufacture of various esters (both synthetic and naturally occurring), such as octyl acetate, which are used in perfumery and flavors. Other uses include experimental medical applications utilizing octanol to control certain types of involuntary tremors.[1]
## Water/ octanol partitioning
Octanol and water are immiscible. The distribution of a compound between water and octanol is used to calculate the partition coefficient 'P' of that molecule (often expressed as its logarithm to the base 10, log P). Water/ octanol partitioning is a good approximation of the partitioning between the cytosol and lipid membranes of living systems.[citation needed]
Many dermal absorption models consider the stratum corneum/ water partition coefficient to be well approximated by a function of the water/ octanol partition coefficient of the form
[2]:
Where a and b are constants,<math>K_{sc/w}</math> is the stratum corneum/ water partition coefficient, and<math>K_{o/w}</math> is the water/ octanol partition coefficient. The values of a and b vary between papers, but Cleek & Bunge
[3]
have reported the values a=0, b=0.74. | https://www.wikidoc.org/index.php/Octanol | |
1eeb7e728b7f5ff13fa41f9fa3b42eb1e6ad8064 | wikidoc | Oestrus | Oestrus
The estrous cycle (also oestrous cycle; derived from Latin oestrus and originally from Greek οἶστρος) comprises the recurring physiologic changes that are induced by reproductive hormones in most mammalian placental females. Humans undergo a menstrual cycle instead. Estrous cycles start after puberty in sexually mature females and are interrupted by anestrous phases. Typically estrous cycles continue until death. Some animals may display bloody vaginal discharge, often mistaken for menstruation also called a "period".
# Differences from the menstrual cycle
Mammals share the same reproductive system, including the regulatory hypothalamic system that releases gonadotropin releasing hormone in pulses, the pituitary that secretes follicle stimulating hormone and luteinizing hormone, and the ovary itself releases sex hormones including estrogens and progesterone. However, species vary significantly in the detailed functioning. One difference is that animals that have estrous cycles reabsorb the endometrium if conception does not occur during that cycle. Animals that have menstrual cycles shed the endometrium through menstruation instead. Another difference is sexual activity. In species with estrous cycles, females are generally only sexually active during the estrus phase of their cycle (see below for an explanation of the different phases in an estrous cycle). This is also referred to as being "in heat." In contrast, females of species with menstrual cycles can be sexually active at any time in their cycle, even when they are not about to ovulate. Humans, unlike some other species, do not have any obvious external signs to signal estral receptivity at ovulation (concealed ovulation). Recent research suggests, however, that women tend to have more sexual thoughts and are far more prone to sexual activity right before ovulation (estrus).
# Etymology and nomenclature
Estrus is derived via Latin oestrus (frenzy, gadfly), from Greek οιστρος (gadfly, breeze, sting, mad impulse). Specifically, this refers to the gadfly that Hera sent to torment Io, who had been won in her heifer form by Zeus. Euripides used "oestrus" to indicate "frenzy", and to describe madness. Homer uses the word to describe panic. Plato also uses it to refer to an irrational drive and to describe the soul "driven and drawn by the gadfly of desire". Somewhat more closely aligned to current meaning and usage of "estrus", Herodotus (Histories ch.93.1) uses oistros to describe the desire of fish to spawn.
The earliest use in English is of "frenzied passion". In 1900 it was first used to describe "rut in animals, heat".
In British English, the spelling is oestrus or œstrus. In all English spellings it has a '-us' ending when used as a noun and an '-ous' spelling when used as an adjective. Thus (in American English) a mammal (humans included) may be described as 'in estrus' when it is in that particular part of the estrous or menstrual cycle. Estrum is sometimes used as a synonym for estrus.
# The four phases of the estrous cycle
## Proestrus
One or several follicles of the ovary are starting to grow. Their number is specific for the species. Typically this phase can last as little as one day or as long as 3 weeks, depending on the species. Under the influence of estrogen the lining in the uterus (endometrium) starts to develop. Some animals may experience vaginal secretions that could be bloody. The female is not yet sexually receptive.
## Estrus
Estrus refers to the phase when the female is sexually receptive ("in heat," or "on heat" in British English). Under regulation by gonadotropic hormones, ovarian follicles are maturing and estrogen secretions exert their biggest influence. The animal exhibits a sexually receptive behavior, a situation that may be signaled by visible physiologic changes. A signal trait of estrus is the lordosis reflex, in which the animal spontaneously elevates her hindquarters.
In some species, the vulvae are reddened. Ovulation may occur spontaneously in some species (e.g. cow), while in others it is induced by copulation (e.g. cat). If there is no copulation in an induced ovulator, estrus may continue for many days, followed by 'interestrus,' and the estrus phase starts again until copulation and ovulation occur.
## Metestrus
During this phase, the signs of estrogen stimulation subside and the corpus luteum starts to form. The uterine lining begins to secrete small amounts of progesterone. This phase typically is brief and may last 1 to 5 days. In some animals bleeding may be noted due to declining estrogen levels.
## Diestrus
Diestrus is characterised by the activity of the corpus luteum that produces progesterone. In the absence of pregnancy the diestrus phase (also termed pseudo-pregnancy) terminates with the regression of the corpus luteum. The lining in the uterus is not shed, but will be reorganised for the next cycle.
# Anestrus
Anestrus refers to the phase when the sexual cycle rests. This is typically a seasonal event and controlled by light exposure through the pineal gland that releases melatonin. Melatonin may repress stimulation of reproduction in long-day breeders and stimulate reproduction in short-day breeders. Melatonin is thought to act by regulating hypothalamic pulse activity of GnRH. Anestrus is induced by time of year, pregnancy, lactation, significant illness, and possibly age.
# Cycle variability
Cycle variability differs among species, but typically cycles are more frequent in smaller animals. Even within species significant variability can be observed, thus cats may undergo an estrous cycle of 3 to 7 weeks. Domestication can affect estrous cycles due to changes in the environment.
# Frequency
Some species, such as cats, cows and pigs, are polyestrous and can go into heat several times a year. Seasonally polyestrous animals have more than one estrous cycles during a specific time of the year and can be divided into short-day and long-day breeders:
- Short-day breeders, such as sheep, goats, deer, foxes, elk—are sexually active in fall or winter.
- Long-day breeders, such as horses and hamsters, are sexually active in spring and summer.
Species that go into heat twice per year, such as most dogs, are diestrous.
Monoestrous species, such as bears, foxes, and wolves, have only one breeding season a year, typically in spring to allow growth of the offspring during the warm season to survive the next winter.
A few mammalian species, such as rabbits, do not have an estrous cycle and are able to conceive at almost any arbitrary moment.
# Specific species
## Cats
The female cat in heat has an estrus of 14-21 days and is an induced ovulator. Without copulation she may enter interestrus before reentering estrus. With copulation and in the absence of pregnancy, cycles occur about every three weeks. Cats are polyestrous but experience a seasonal anestrus in autumn and late winter.
## Dogs
A female dog is diestrous and goes into heat typically twice every year, although some breeds typically have one or three cycles a year. The proestrus is relatively long at 5-7 days, while the estrus may last 4-13 days. With a diestrus of 7-10 days, a typical cycle lasts about 3 weeks followed by about 150 days of anestrus. They bleed during this time, which will usually last from 7-13 days, depending on the size and maturity of the dog.
## Horses
For more information, see the article on Horse reproduction.
A mare may be 4 to 10 days in heat and about 14 days in diestrus. Thus a cycle may be short, i.e. 3 weeks. Horses mate in spring and summer, autumn is a transition time, and anestrus rules the winter.
A feature of the fertility cycle of horses and other large herd animals is that it is usually affected by the seasons. The number of hours daily that light enters the eye of the animal affects the brain, which governs the release of certain precursors and hormones. When daylight hours are few, these animals "shut down," become anestrous, and do not become fertile. As the days grow longer, the longer periods of daylight cause the hormones which activate the breeding cycle to be released. As it happens, this has a sort of utility for these animals in that, given a gestation period of about eleven months, it prevents them from having young when the cold of winter would make their survival risky. This is why animals can reproduce during only certain times of the year.
## Rats
Rats typically have rapid cycle times of 4 to 5 days. Although they ovulate spontaneously, they do not develop a fully functioning corpus luteum unless they receive coital stimulation. Fertile mating leads to pregnancy in this way, but infertile mating leads to a state of pseudopregnancy which lasts about 10 days. Mice and hamsters have similar behaviour. The events of the cycle are strongly influenced by lighting periodicity.
A set of follicles start to develop near the end of proestrus and grow at a nearly constant rate until the beginning of the subsequent estrus when the growth rates accelerate eightfold. They then ovulate about 109 hours after starting growth.
Oestrogen peaks at about 11am on the day of proestrus. Between then and midnight there is a surge in progesterone, LH and FSH, and ovulation occurs at about 4am on the next, estrus day. The following day, metestrus, is called early diestrus or diestrus I by some authors. During this day the corpus lutea grow to a maximal volume, achieved within 24 hours of ovulation. They remain at that size for 3 days, halve in size before the metestrus of the next cycle and then shrink abruptly before estrus of the cycle after that. Thus the ovaries of cycling rats contain three different sets of corpora lutea at different phases of development.
## Others
Estrus frequencies of some other mammals:
- Ewe - 17 days
- Bovine - 21 days
- Goat - 21 days
- Sow - 21 days
- Elephant - 16 weeks | Oestrus
The estrous cycle (also oestrous cycle; derived from Latin oestrus and originally from Greek οἶστρος) comprises the recurring physiologic changes that are induced by reproductive hormones in most mammalian placental females. Humans undergo a menstrual cycle instead. Estrous cycles start after puberty in sexually mature females and are interrupted by anestrous phases. Typically estrous cycles continue until death. Some animals may display bloody vaginal discharge, often mistaken for menstruation also called a "period".
# Differences from the menstrual cycle
Mammals share the same reproductive system, including the regulatory hypothalamic system that releases gonadotropin releasing hormone in pulses, the pituitary that secretes follicle stimulating hormone and luteinizing hormone, and the ovary itself releases sex hormones including estrogens and progesterone. However, species vary significantly in the detailed functioning. One difference is that animals that have estrous cycles reabsorb the endometrium if conception does not occur during that cycle. Animals that have menstrual cycles shed the endometrium through menstruation instead. Another difference is sexual activity. In species with estrous cycles, females are generally only sexually active during the estrus phase of their cycle (see below for an explanation of the different phases in an estrous cycle). This is also referred to as being "in heat." In contrast, females of species with menstrual cycles can be sexually active at any time in their cycle, even when they are not about to ovulate. Humans, unlike some other species, do not have any obvious external signs to signal estral receptivity at ovulation (concealed ovulation). Recent research[1] suggests, however, that women tend to have more sexual thoughts and are far more prone to sexual activity right before ovulation (estrus).
[2]
# Etymology and nomenclature
Estrus is derived via Latin oestrus (frenzy, gadfly), from Greek οιστρος (gadfly, breeze, sting, mad impulse). Specifically, this refers to the gadfly that Hera sent to torment Io, who had been won in her heifer form by Zeus. Euripides used "oestrus" to indicate "frenzy", and to describe madness. Homer uses the word to describe panic[3]. Plato also uses it to refer to an irrational drive[4] and to describe the soul "driven and drawn by the gadfly of desire"[5]. Somewhat more closely aligned to current meaning and usage of "estrus", Herodotus (Histories ch.93.1) uses oistros to describe the desire of fish to spawn[6].
The earliest use in English is of "frenzied passion". In 1900 it was first used to describe "rut in animals, heat".[7][8]
In British English, the spelling is oestrus or œstrus. In all English spellings it has a '-us' ending when used as a noun and an '-ous' spelling when used as an adjective. Thus (in American English) a mammal (humans included) may be described as 'in estrus' when it is in that particular part of the estrous or menstrual cycle. Estrum is sometimes used as a synonym for estrus.
# The four phases of the estrous cycle
## Proestrus
One or several follicles of the ovary are starting to grow. Their number is specific for the species. Typically this phase can last as little as one day or as long as 3 weeks, depending on the species. Under the influence of estrogen the lining in the uterus (endometrium) starts to develop. Some animals may experience vaginal secretions that could be bloody. The female is not yet sexually receptive.
## Estrus
Estrus refers to the phase when the female is sexually receptive ("in heat," or "on heat" in British English). Under regulation by gonadotropic hormones, ovarian follicles are maturing and estrogen secretions exert their biggest influence. The animal exhibits a sexually receptive behavior, a situation that may be signaled by visible physiologic changes. A signal trait of estrus is the lordosis reflex, in which the animal spontaneously elevates her hindquarters.
In some species, the vulvae are reddened. Ovulation may occur spontaneously in some species (e.g. cow), while in others it is induced by copulation (e.g. cat). If there is no copulation in an induced ovulator, estrus may continue for many days, followed by 'interestrus,' and the estrus phase starts again until copulation and ovulation occur.
## Metestrus
During this phase, the signs of estrogen stimulation subside and the corpus luteum starts to form. The uterine lining begins to secrete small amounts of progesterone. This phase typically is brief and may last 1 to 5 days. In some animals bleeding may be noted due to declining estrogen levels.
## Diestrus
Diestrus is characterised by the activity of the corpus luteum that produces progesterone. In the absence of pregnancy the diestrus phase (also termed pseudo-pregnancy) terminates with the regression of the corpus luteum. The lining in the uterus is not shed, but will be reorganised for the next cycle.
# Anestrus
Anestrus refers to the phase when the sexual cycle rests. This is typically a seasonal event and controlled by light exposure through the pineal gland that releases melatonin. Melatonin may repress stimulation of reproduction in long-day breeders and stimulate reproduction in short-day breeders. Melatonin is thought to act by regulating hypothalamic pulse activity of GnRH. Anestrus is induced by time of year, pregnancy, lactation, significant illness, and possibly age.
# Cycle variability
Cycle variability differs among species, but typically cycles are more frequent in smaller animals. Even within species significant variability can be observed, thus cats may undergo an estrous cycle of 3 to 7 weeks. Domestication can affect estrous cycles due to changes in the environment.
# Frequency
Some species, such as cats, cows and pigs, are polyestrous and can go into heat several times a year. Seasonally polyestrous animals have more than one estrous cycles during a specific time of the year and can be divided into short-day and long-day breeders:
- Short-day breeders, such as sheep, goats, deer, foxes, elk—are sexually active in fall or winter.
- Long-day breeders, such as horses and hamsters, are sexually active in spring and summer.
Species that go into heat twice per year, such as most dogs, are diestrous.
Monoestrous species, such as bears, foxes, and wolves, have only one breeding season a year, typically in spring to allow growth of the offspring during the warm season to survive the next winter.
A few mammalian species, such as rabbits, do not have an estrous cycle and are able to conceive at almost any arbitrary moment.
# Specific species
## Cats
The female cat in heat has an estrus of 14-21 days and is an induced ovulator. Without copulation she may enter interestrus before reentering estrus. With copulation and in the absence of pregnancy, cycles occur about every three weeks. Cats are polyestrous but experience a seasonal anestrus in autumn and late winter.
## Dogs
A female dog is diestrous and goes into heat typically twice every year, although some breeds typically have one or three cycles a year. The proestrus is relatively long at 5-7 days, while the estrus may last 4-13 days. With a diestrus of 7-10 days, a typical cycle lasts about 3 weeks followed by about 150 days of anestrus. They bleed during this time, which will usually last from 7-13 days, depending on the size and maturity of the dog.
## Horses
For more information, see the article on Horse reproduction.
A mare may be 4 to 10 days in heat and about 14 days in diestrus. Thus a cycle may be short, i.e. 3 weeks. Horses mate in spring and summer, autumn is a transition time, and anestrus rules the winter.
A feature of the fertility cycle of horses and other large herd animals is that it is usually affected by the seasons. The number of hours daily that light enters the eye of the animal affects the brain, which governs the release of certain precursors and hormones. When daylight hours are few, these animals "shut down," become anestrous, and do not become fertile. As the days grow longer, the longer periods of daylight cause the hormones which activate the breeding cycle to be released. As it happens, this has a sort of utility for these animals in that, given a gestation period of about eleven months, it prevents them from having young when the cold of winter would make their survival risky. This is why animals can reproduce during only certain times of the year.
## Rats
Rats typically have rapid cycle times of 4 to 5 days. Although they ovulate spontaneously, they do not develop a fully functioning corpus luteum unless they receive coital stimulation. Fertile mating leads to pregnancy in this way, but infertile mating leads to a state of pseudopregnancy which lasts about 10 days. Mice and hamsters have similar behaviour.[9] The events of the cycle are strongly influenced by lighting periodicity.[7]
A set of follicles start to develop near the end of proestrus and grow at a nearly constant rate until the beginning of the subsequent estrus when the growth rates accelerate eightfold. They then ovulate about 109 hours after starting growth.
Oestrogen peaks at about 11am on the day of proestrus. Between then and midnight there is a surge in progesterone, LH and FSH, and ovulation occurs at about 4am on the next, estrus day. The following day, metestrus, is called early diestrus or diestrus I by some authors. During this day the corpus lutea grow to a maximal volume, achieved within 24 hours of ovulation. They remain at that size for 3 days, halve in size before the metestrus of the next cycle and then shrink abruptly before estrus of the cycle after that. Thus the ovaries of cycling rats contain three different sets of corpora lutea at different phases of development. [10]
## Others
Estrus frequencies of some other mammals:
- Ewe - 17 days
- Bovine - 21 days
- Goat - 21 days
- Sow - 21 days
- Elephant - 16 weeks | https://www.wikidoc.org/index.php/Oestrus | |
b3bc4f7e00c580ce7bf662bdbbb13c7e68b8105f | wikidoc | Okclipo | Okclipo
OKC Lipo is a Cosmetic Surgery group based in Oklahoma that offers “lunchtime” or “awake” liposuction treatments. It is one of the Cosmetic Surgery practices in Oklahoma employed as a test market for numerous makers of liposuction equipment. OKC Lipo is an exclusive Midwest training center (OK, NM, CO, AR, NE, KS) for such manufacturers. Training on matters of safety, getting quality results, and effectiveness is imparted to other physicians.
# OVERVIEW
The variety of liposuction procedures performed aims at making the most of the patient’s anatomy and improving his/her beauty for a youthful appearance. Traditional, power-assisted, Vaser ultrasonic or laser liposuction methods are adopted to lessen fat and tone the body in a safe manner. The regions treated with “lunchtime/local lipo” are the love handles or waist, thighs (outer and inner), abdomen, arms, male chest, hips, chin, and knees. Other treatable areas are banana roll, bra rolls, neck, buffalo hump, saddle bags, calves, ankles, buttocks, male pubic, jowls, and male breasts.
# History
A rising demand for the services of OKC Lipo caused the practice to shift to their sophisticated surgical facility, situated on the same area as that of Cosmetic Surgery Affiliates.
## Medical Team
### Dr. Miller
Dr. Miller received his medical degree from the Oklahoma School of Medicine. By way of Texas A & M, he finished a General Surgery Residency of 5 years duration, finally entering into the famous Scott & White Hospital, Temple, Texas as a Staff Surgeon (Trauma Surgery). This was followed by a year of training under Dr. Angelo Cuzalina in Tulsa, Oklahoma, Dr. Miller’s mentor, for fellowship training specifically in Cosmetic Surgery.
Dr. Miller educates physicians from all over the US who handle Cosmetic Surgery. He delivers lectures nationwide on the different kinds of liposuction. He is board-certified in General Surgery and Cosmetic Surgery. He is a member of the American Medical Association, the American Academy of Cosmetic Surgeons, and the Texas Medical Association. He is a prospective member of the American College of Surgeons. He has an affiliation with Leutronic Liposuction to provide special training in learning liposuction methods to regional physicians.
### Dr. Nuveen
Dr. Nuveen possesses subspecialized fellowship training in Cosmetic Surgery. He possesses dental and medical graduate degrees, the former from a dental school considered to be the best in the US – University of Connecticut School of Dental Medicine, and the latter from the esteemed Case Western University School of Medicine. He did an extra year of general surgery at Penn State/Hershey Medical Center.
Dr. Nuveen is a global Cosmetic Surgery instructor and much of his professional life is spent in the Cosmetic Surgery training and instruction for physicians from different parts of the world. He has done research in rheumatology and immunology. The doctor’s practice is the biggest in Oklahoma having 5 locations. In addition, it has hospital privileges to perform all the doctor’s procedures within or outside the hospital.
Dr. Nuveen was taken in for a fellowship accredited by the American Academy of Cosmetic Surgery, in Cosmetic Surgery of the face and body in Salt Lake City, Utah.
# Liposection
Liposuction is one of the most well-liked and safest procedures for body contouring in the world. Its popularity can be attributed to the fact that any surplus body fat (trouble areas) that does not get reduced despite doing exercise and watching food intake, can be easily, quickly, and permanently removed with this procedure. It also tightens loose skin, and helps to improve male and female body contours. Areas that can be worked on include the face, breasts/chest, hips, knees, abdomen, neck, ankles, upper arms, and thighs. Fat can be removed from one or multiple areas simultaneously.
Little incisions are made in natural skin creases or hair bearing regions. Following this, a special tumescent solution is introduced within the trouble areas to be a local anesthetic and control blood loss. A cannula that is connected to a suction machine by way of tubing is then used to get rid of the excess fat (now in melted form) from the particular fatty area(s). How long the procedure would take would depend on how much fat is involved and how difficult the process is for a particular patient. Results from the procedure are also variable. A compression garment limits surgical trauma, and helps with retraction of any flabby skin. Most patients get back to their regular lifestyle within a couple of days.
## Laser-Assisted Lipolysis
Stubborn fat, settled in big regions or localized is removed using an FDA approved body sculpting device (AccuSculpt laser lipo-sculpting system) and the energy of its wavelength of frequency 1444 nm which causes emulsification. The patient is administered local anesthesia before the procedure which is stated to be fast, minimally invasive, causing minimal surgical trauma, and facilitating a speedy recovery. Most body regions can be treated including face, flanks, arms, neck, back, abdomen, inner thighs, knees, and buttocks.
## Power-Assisted Liposuction
A minimally invasive liposuction procedure is carried out to treat big regions containing obstinate fat deposits. For the purpose, a power aided device (MicroAire Power-Assisted Liposculptor) is made use of. Fat is loosened by way of the device’s 2 mm cannula which vibrates at the rate of 4000 cycles a minute. Liposuction with this device has been stated by the practice to be safe as it doesn’t depend on heat energy that could cause surgical trauma, it causes minimal uneasiness and pain, and doesn’t require the application of a lot of pressure or force. Both anesthetic and salt solutions are introduced into the concerned area to limit discomfort and pain. Difficult regions such as the male breasts, flanks, and inner thighs are treatable with this procedure.
## Ultrasound Assisted Liposuction
This is a procedure generally used for fat removal from dense regions of the body and for reducing the size of the breasts. It is for taking away fat from particular body areas. The method adopted by the practice is the VASER Ultrasonic Liposuction system which is suitable for both delicate body regions such as the chin, inner thighs, arms, and neck, and also regions of a less fragile nature. The ultrasound energy gets rid of the redundant fat deposits. It does not hurt vital structures such as the blood vessels and nerves. The VASER Hi Def method is used to improve the appearance of the natural body contours.
## Traditional Liposuction
It is an outpatient procedure that is often carried out using local anesthesia. It can cause permanent changes in the contours of the body in areas where surplus fat deposits cause rounding or protruding in a body structure that is otherwise balanced. The procedure is not suitable for the removal of cellulite. The ultrasonic method is preferable to this conventional method in cases where the patient has a lot of skin. The best candidates for this procedure would be adults within 30% of the correct weight for them and having elastic, firm skin with good muscle tone.
# PRE-PROCEDURE FORMALITIES
Before surgery can be done, patients have to submit signed forms showing that they have been advised on possible surgical complications because of a smoking habit; have consented to have photographs taken of themselves, or of their body parts; and have agreed to the surgery after having read through the possible risks, and so on. Information relating to the procedure is available for downloading by patients from the OKC Lipo website. | Okclipo
OKC Lipo is a Cosmetic Surgery group based in Oklahoma that offers “lunchtime” or “awake” liposuction treatments. It is one of the Cosmetic Surgery practices in Oklahoma employed as a test market for numerous makers of liposuction equipment. OKC Lipo is an exclusive Midwest training center (OK, NM, CO, AR, NE, KS) for such manufacturers. Training on matters of safety, getting quality results, and effectiveness is imparted to other physicians.
# OVERVIEW
The variety of liposuction procedures performed aims at making the most of the patient’s anatomy and improving his/her beauty for a youthful appearance. Traditional, power-assisted, Vaser ultrasonic or laser liposuction methods are adopted to lessen fat and tone the body in a safe manner. The regions treated with “lunchtime/local lipo” are the love handles or waist, thighs (outer and inner), abdomen, arms, male chest, hips, chin, and knees. Other treatable areas are banana roll, bra rolls, neck, buffalo hump, saddle bags, calves, ankles, buttocks, male pubic, jowls, and male breasts.
# History
A rising demand for the services of OKC Lipo caused the practice to shift to their sophisticated surgical facility, situated on the same area as that of Cosmetic Surgery Affiliates.
## Medical Team
### Dr. Miller
Dr. Miller received his medical degree from the Oklahoma School of Medicine. By way of Texas A & M, he finished a General Surgery Residency of 5 years duration, finally entering into the famous Scott & White Hospital, Temple, Texas as a Staff Surgeon (Trauma Surgery). This was followed by a year of training under Dr. Angelo Cuzalina in Tulsa, Oklahoma, Dr. Miller’s mentor, for fellowship training specifically in Cosmetic Surgery.
Dr. Miller educates physicians from all over the US who handle Cosmetic Surgery. He delivers lectures nationwide on the different kinds of liposuction. He is board-certified in General Surgery and Cosmetic Surgery. He is a member of the American Medical Association, the American Academy of Cosmetic Surgeons, and the Texas Medical Association. He is a prospective member of the American College of Surgeons. He has an affiliation with Leutronic Liposuction to provide special training in learning liposuction methods to regional physicians.
### Dr. Nuveen
Dr. Nuveen possesses subspecialized fellowship training in Cosmetic Surgery. He possesses dental and medical graduate degrees, the former from a dental school considered to be the best in the US – University of Connecticut School of Dental Medicine, and the latter from the esteemed Case Western University School of Medicine. He did an extra year of general surgery at Penn State/Hershey Medical Center.
Dr. Nuveen is a global Cosmetic Surgery instructor and much of his professional life is spent in the Cosmetic Surgery training and instruction for physicians from different parts of the world. He has done research in rheumatology and immunology. The doctor’s practice is the biggest in Oklahoma having 5 locations. In addition, it has hospital privileges to perform all the doctor’s procedures within or outside the hospital.
Dr. Nuveen was taken in for a fellowship accredited by the American Academy of Cosmetic Surgery, in Cosmetic Surgery of the face and body in Salt Lake City, Utah.
# Liposection
Liposuction is one of the most well-liked and safest procedures for body contouring in the world. Its popularity can be attributed to the fact that any surplus body fat (trouble areas) that does not get reduced despite doing exercise and watching food intake, can be easily, quickly, and permanently removed with this procedure. It also tightens loose skin, and helps to improve male and female body contours. Areas that can be worked on include the face, breasts/chest, hips, knees, abdomen, neck, ankles, upper arms, and thighs. Fat can be removed from one or multiple areas simultaneously.
Little incisions are made in natural skin creases or hair bearing regions. Following this, a special tumescent solution is introduced within the trouble areas to be a local anesthetic and control blood loss. A cannula that is connected to a suction machine by way of tubing is then used to get rid of the excess fat (now in melted form) from the particular fatty area(s). How long the procedure would take would depend on how much fat is involved and how difficult the process is for a particular patient. Results from the procedure are also variable. A compression garment limits surgical trauma, and helps with retraction of any flabby skin. Most patients get back to their regular lifestyle within a couple of days.
## Laser-Assisted Lipolysis
Stubborn fat, settled in big regions or localized is removed using an FDA approved body sculpting device (AccuSculpt laser lipo-sculpting system) and the energy of its wavelength of frequency 1444 nm which causes emulsification. The patient is administered local anesthesia before the procedure which is stated to be fast, minimally invasive, causing minimal surgical trauma, and facilitating a speedy recovery. Most body regions can be treated including face, flanks, arms, neck, back, abdomen, inner thighs, knees, and buttocks.
## Power-Assisted Liposuction
A minimally invasive liposuction procedure is carried out to treat big regions containing obstinate fat deposits. For the purpose, a power aided device (MicroAire Power-Assisted Liposculptor) is made use of. Fat is loosened by way of the device’s 2 mm cannula which vibrates at the rate of 4000 cycles a minute. Liposuction with this device has been stated by the practice to be safe as it doesn’t depend on heat energy that could cause surgical trauma, it causes minimal uneasiness and pain, and doesn’t require the application of a lot of pressure or force. Both anesthetic and salt solutions are introduced into the concerned area to limit discomfort and pain. Difficult regions such as the male breasts, flanks, and inner thighs are treatable with this procedure.
## Ultrasound Assisted Liposuction
This is a procedure generally used for fat removal from dense regions of the body and for reducing the size of the breasts. It is for taking away fat from particular body areas. The method adopted by the practice is the VASER Ultrasonic Liposuction system which is suitable for both delicate body regions such as the chin, inner thighs, arms, and neck, and also regions of a less fragile nature. The ultrasound energy gets rid of the redundant fat deposits. It does not hurt vital structures such as the blood vessels and nerves. The VASER Hi Def method is used to improve the appearance of the natural body contours.
## Traditional Liposuction
It is an outpatient procedure that is often carried out using local anesthesia. It can cause permanent changes in the contours of the body in areas where surplus fat deposits cause rounding or protruding in a body structure that is otherwise balanced. The procedure is not suitable for the removal of cellulite. The ultrasonic method is preferable to this conventional method in cases where the patient has a lot of skin. The best candidates for this procedure would be adults within 30% of the correct weight for them and having elastic, firm skin with good muscle tone.
# PRE-PROCEDURE FORMALITIES
Before surgery can be done, patients have to submit signed forms showing that they have been advised on possible surgical complications because of a smoking habit; have consented to have photographs taken of themselves, or of their body parts; and have agreed to the surgery after having read through the possible risks, and so on. Information relating to the procedure is available for downloading by patients from the OKC Lipo website.
# External links
- Website : okclipo.com | https://www.wikidoc.org/index.php/Okclipo | |
bf834653b55630367ac0b6a19da9dc42b6b79739 | wikidoc | Olaflur | Olaflur
# Overview
Olaflur (INN, or amine fluoride 297) is a fluoride-containing substance that is an ingredient of toothpastes and solutions for the prevention of dental caries. It has been in use since 1966. Especially in combination with dectaflur, it is also used in the form of gels for the treatment of early stages of caries, sensitive teeth, and by dentists for the refluoridation of damaged tooth enamel.
# Overdosage
Overdosage leads to irritation of the oral mucosa. In especially sensitive persons, even standard doses of olaflur can cause irritation.
Like other fluoride salts, olaflur is toxic when given in high doses over an extended period of time. Especially in children, before the development of the permanent teeth, overdosage can lead to dental fluorosis, a discolouring and weakening of the enamel. In acute cases of overdosage, for example when an olaflur containing preparation is swallowed, calcium in any oral form serves as an antidote. Often milk is used because it is usually at hand.
# Interactions
Because calcium fluoride is practically insoluble in water, calcium-containing drugs and food inhibit the action of olaflur.
# Chemistry and mechanism of action
Olaflur is a salt consisting of an alkyl ammonium cation and fluoride as the counterion. With a long lipophilic hydrocarbon chain, the cation has surfactant properties. It forms a film layer on the surface of teeth, which facilitates incorporation of fluoride into the enamel. The top layers of the enamel's primary mineral, hydroxylapatite, are converted into the more robust fluorapatite. The fluoridation reaches only a depth of a few nanometres, which has raised doubts whether the mechanism really relies on the formation of fluorapatite.
## Synthesis
The synthesis of olaflur starts from cattle's tallow. The contained fatty acids, mainly stearic acid (C17H35COOH), are obtained by hydrolysis, and then converted to the corresponding amides, which in turn are reduced catalytically to the primary amines. Addition of acrylonitrile, followed by another reduction, yields N-alkyl-1,3-propanediamines. The two nitrogen atoms react with ethylene oxide (oxirane) to tertiary amines. Finally, hydrofluoric acid is added to give the end product. Because olaflur is produced from a mixture of fatty acids, some molecules have side chains that are longer or shorter than 18 carbon atoms. Other byproducts of the reaction include hydroxyethyl ethers resulting from addition of ethylene oxide to the free hydroxyl groups. The presence of these side products is clinically irrelevant. | Olaflur
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Olaflur (INN, or amine fluoride 297) is a fluoride-containing substance that is an ingredient of toothpastes and solutions for the prevention of dental caries.[1] It has been in use since 1966. Especially in combination with dectaflur, it is also used in the form of gels for the treatment of early stages of caries, sensitive teeth, and by dentists for the refluoridation of damaged tooth enamel.[2]
# Overdosage
Overdosage leads to irritation of the oral mucosa. In especially sensitive persons, even standard doses of olaflur can cause irritation.[2]
Like other fluoride salts, olaflur is toxic when given in high doses over an extended period of time. Especially in children, before the development of the permanent teeth, overdosage can lead to dental fluorosis, a discolouring and weakening of the enamel.[3] In acute cases of overdosage, for example when an olaflur containing preparation is swallowed, calcium in any oral form serves as an antidote. Often milk is used because it is usually at hand.[2]
# Interactions
Because calcium fluoride is practically insoluble in water, calcium-containing drugs and food inhibit the action of olaflur.[2]
# Chemistry and mechanism of action
Olaflur is a salt consisting of an alkyl ammonium cation and fluoride as the counterion. With a long lipophilic hydrocarbon chain, the cation has surfactant properties. It forms a film layer on the surface of teeth, which facilitates incorporation of fluoride into the enamel. The top layers of the enamel's primary mineral, hydroxylapatite, are converted into the more robust fluorapatite. The fluoridation reaches only a depth of a few nanometres, which has raised doubts whether the mechanism really relies on the formation of fluorapatite.[4]
## Synthesis
The synthesis of olaflur starts from cattle's tallow.[5] The contained fatty acids, mainly stearic acid (C17H35COOH), are obtained by hydrolysis, and then converted to the corresponding amides, which in turn are reduced catalytically to the primary amines. Addition of acrylonitrile, followed by another reduction, yields N-alkyl-1,3-propanediamines. The two nitrogen atoms react with ethylene oxide (oxirane) to tertiary amines. Finally, hydrofluoric acid is added to give the end product. Because olaflur is produced from a mixture of fatty acids, some molecules have side chains that are longer or shorter than 18 carbon atoms. Other byproducts of the reaction include hydroxyethyl ethers resulting from addition of ethylene oxide to the free hydroxyl groups. The presence of these side products is clinically irrelevant.[5] | https://www.wikidoc.org/index.php/Olaflur | |
b95483a7f5d2893decaa806055eaef0250da6b41 | wikidoc | Onychia | Onychia
Synonyms and keywords: Onychosis
# Overview
Onychia is an inflammation of the matrix (surrounding tissue) of the nail with formation of pus and shedding of the nail.
# Pathophysiology
Onychia results from the introduction of microscopic pathogens through small wounds.
# Causes
## Common Causes
Onychia can be caused by manicuring instruments that have not been properly disinfected. | Onychia
Template:DiseaseDisorder infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Onychosis
# Overview
Onychia is an inflammation of the matrix (surrounding tissue) of the nail with formation of pus and shedding of the nail.
# Pathophysiology
Onychia results from the introduction of microscopic pathogens through small wounds.
# Causes
## Common Causes
Onychia can be caused by manicuring instruments that have not been properly disinfected. | https://www.wikidoc.org/index.php/Onychia | |
763b902c52f45c84d42ea2a730b99e39aa666765 | wikidoc | Onyx-15 | Onyx-15
Onyx 015 is an experimental intratumoral adenovirus, genetically modified from its original cold virus form.
In its unattenuated form, the adenovirus blocks the cell-cycle control protein p53, using the E1B protein, then replicates in the cell it has attacked, and causes lysis, enabling it to spread and infect other cells.
When modified to the Onyx 015 form (E1B-55kDa-deleted), the virus lacks the E1B protein, and so upon infection p53 can block viral replication and initiate cell cycle arrest, and the virus is unable to spread.
However in cancerous cells which lack p53, the virus is still able to replicate. Thus the tumour cells will undergo lysis whilst the healthy surrounding cells are safe.
# Chemotherapeutic Use
Onyx 015 has been used experimentally for combatting head and neck tumours, in combination with the standard chemotherapeutic agents cisplatin and 5-fluorouracil | Onyx-15
Onyx 015 is an experimental intratumoral adenovirus, genetically modified from its original cold virus form.[1]
In its unattenuated form, the adenovirus blocks the cell-cycle control protein p53, using the E1B protein, then replicates in the cell it has attacked, and causes lysis, enabling it to spread and infect other cells.
When modified to the Onyx 015 form (E1B-55kDa-deleted), the virus lacks the E1B protein, and so upon infection p53 can block viral replication and initiate cell cycle arrest, and the virus is unable to spread.
However in cancerous cells which lack p53, the virus is still able to replicate. Thus the tumour cells will undergo lysis whilst the healthy surrounding cells are safe.
# Chemotherapeutic Use
Onyx 015 has been used experimentally for combatting head and neck tumours, in combination with the standard chemotherapeutic agents cisplatin and 5-fluorouracil [2] | https://www.wikidoc.org/index.php/Onyx-15 | |
0a068c872f32f8fc6e135682a860e54aa3294bc8 | wikidoc | Surgery | Surgery
# Overview
In medicine, surgery (from the Greek error: {{lang}}: text has italic markup (help) and latin error: {{lang}}: text has italic markup (help) meaning "hand work") is a medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance, or sometimes for some other reason. An act of performing surgery may be called a surgical procedure, operation, or simply surgery. In this context, the verb operating means performing surgery. The adjective surgical means pertaining to surgery; e.g. surgical instruments or surgical nurse. The patient or subject that the surgery is being performed on can be a person or an animal. A surgeon is a person who performs surgery on patients. Persons described as surgeons are commonly medical practitioners, but the term is also applied to dentists and veterinarians. Surgery can last from minutes to hours, but is typically not an ongoing or periodic type of treatment.
The term surgery can also refer to the place where surgery is performed, or simply the office of a physician, dentist, or veterinarian.
# Overview of modern surgery
Although it is sometimes difficult to determine when a medical procedure is considered surgery, a medical treatment that involves a cutting of a patient's live tissue (e.g., hair and nails are dead tissue) is usually considered surgery of some sort. A medical procedure involving a drilling of live tissue in a body would often be considered surgery, but mere piercing of a body is not necessarily surgery since piercing is often done for taking samples or draining fluids from or injecting materials into the body, or setting up intravenous drip, and usually does not require suturing to close the pierced opening. Even if a medical procedure or treatment does not include cutting or drilling of live tissue in a body, it may be considered surgery, if it involves common surgical procedure or a setting, such as use of an operating room or table in a hospital, anesthesia, antiseptic conditions, typical surgical instruments, and suturing or stapling. Surgery is considered an invasive procedure. Examples of surgery without cutting the body may include debridement or closing (suturing or stapling) an open wound or applying skin grafts if done under typical surgical conditions. Many types of more complicated or involved surgery are obviously considered surgery, since they involve common surgical procedure or setting as mentioned above. A medical procedure may be surgery even if not all of the typical surgical conditions or procedures mentioned above are used.
## A few general types of surgery
Surgery can be categorized in many ways, a few of which are mentioned as follows. Some surgery may be required to save the life of a patient. Elective surgery is surgery not needed to save the life of the patient, but is expected to provide some other benefit. Emergency surgery is surgery which must be done quickly to save life, limb, or other capacity such as eyesight. Exploratory surgery is for investigating a patient's medical condition or making a diagnosis. Therapeutic surgery is for treating a patient. Surgery may start out as exploratory and become therapeutic. Amputation involves cutting off a body part; for example, a limb or digit. Replantation, an often difficult type of surgery more recently developed, involves reattaching a severed body part. Reconstructive surgery involves reconstruction of an injured, mutilated, or deformed part of the body. Reconstructive surgery is for reshaping of certain bodily tissues including bone, cartilage, muscle, fat, and skin that have been previously damanged by trauma or are congenitally abnormal.
Cosmetic surgery, a common type of elective surgery that is done to improve the appearance of the patient. Excision is the cutting out of an organ or other body part from the patient. Transplant surgery is the replacement of an organ or body part by insertion of another from different human (or animal) into the patient. Removing an organ or body part from a live human or animal for use in transplant is also a type of surgery. Minimally invasive surgery involves smaller outer incision(s) to insert some sort of endoscope, which is tube-like equipment, to perform surgery. There are also many types of more specific surgeries. Laser surgery involves use of a laser for cutting tissue instead of a scalpel or similar surgical instruments. Microsurgery is fine surgery with the aid of a microscope for the surgeon to see better. Bariatric surgery is a class of surgery for treating obesity, a common example of which is gastric bypass surgery. Surgery is also used for sterilization to prevent reproduction, although it is a rather simple procedure for males.
Suffixes used for some surgical procedures:
- Excision surgery names often start with a name for the organ to be excised (cut out) and end in -ectomy.
- Procedures involving cutting into an organ or tissue end in -otomy. A surgical procedure cutting through the abdominal wall to gain access to the abdominal cavity is a laparotomy.
- Minimally invasive procedures involving small incisions through which an endoscope is inserted end in -oscopy. For example, such surgery in the abdominal cavity is called laparoscopy.
- Procedures for formation of a permanent or semi-permanent opening called a stoma in the body end in -ostomy.
- Reconstruction or Cosmetic surgery of a body part starts with a name for the body part to be reconstructed and ends in -oplasty. Rhino is used as a prefix for "nose", so rhinoplasty is basically reconstructive or cosmetic surgery for the nose.
For specific examples, see List of surgical procedures.
## Description of surgical procedure
At a hospital, modern surgery is often done in an operating room using surgical instruments, an operating table for the patient, and other equipment. Any surgical instrument which go into the body must be pre-sterilized to avoid infection by micro-organisms. Also to maintain sanitation and sterility, surgeons clean (scrub) their hands. The surgical team wears sterile gloves during surgery. Surgical masks and gowns are also worn.
Modern surgery usually proceeds as follows:
Prior to surgery, particularly if it's non-emergency, the patient is given a medical examination, certain pre-operative tests, an ASA score, and (if satisfactory) a surgical clearance to be operated on. An autologous blood donation may be made a couple weeks prior to surgery to readd in case of blood loss during surgery. If the surgery involves the digestive system, evacuation of the digestive tract with subsequent fasting is done by the patient.
Other preparations for surgery are often done. When the patient enters the operating room, intravenous injection and various instruments to monitor the patient's vital signs are attached. The skin surface to be operated on is cleaned and prepared by shaving hair in area of incision and applying an antiseptic such as betadine to avoid a possibility of infection.
Anesthesia is administered to prevent pain from incision, other tissue cutting and suturing, etc. Although in theory it may sometimes be possible to operate without anesthesia, in most surgeries the pain would be unbearable and a patient would not hold sufficiently still for a surgeon to precisely operate. The anesthesia could be local or general anesthesia. With local anesthesia, the body area operated on is anesthetized, but the patient can remain conscious. With general anesthesia, the patient is rendered unconscious during surgery by an anesthesiologist. The anesthesia is often administered in the form of a drug. For certain serious types of surgery when a muscle relaxant is used, the patient undergoes intubation and is placed on mechanical ventilation using a mechanical ventilator. Intubation is inserting an endotracheal tube into the mouth, through the throat, and into the trachea to provide oxygen to the lungs. Open heart surgery often involves placement of a patient on a heart-lung machine and lowering body temperature so the heart stops beating. When finished, body temperature is raised and, if necessary, an electrical impulse administered to restart the heart.
Then, an incision is made to access the inside of the body area to be worked on. Blood vessels may be clamped to prevent bleeding. Other surgical tools (instruments) may be used to keep the incision open. It is commonly desired to keep the incision as small as possible. Various internal membranes may be cut also for further access inside. In certain cases, bone may be cut to further access the interior of the body; for example, cutting the skull for brain surgery or cutting the sternum for thoracic (chest) surgery to open up the rib cage.
Work to correct the problem in body then proceeds. This work may involve:
- excision - cutting out an organ, tumor, or other body part.
- resection - partial removal of an organ or other bodily structure.
- reconnection of organs, tissues, etc., particularly if severed. Resection of organs such as intestines involves reconnection. Internal suturing or stapling may be used. Surgical connection between blood vessels or other tubular or hollow structures such as loops of intestine is called anastomosis.
- ligation - tying off blood vessels, ducts, or "tubes".
- grafts - may be severed pieces of tissue cut from the same (or different) body or flaps of tissue still partly connected to the body but resewn for rearranging or restructuring of the area of the body in question. Although grafting is often used in cosmetic surgery, it is also used in other surgery. Grafts may be taken from one area of the patient's body and inserted to another area of the body. An example is bypass surgery, where clogged blood vessels are bypassed with a graft from another part of the body. Alternatively, grafts may be from other persons, cadavers, or animals.
- insertion of prosthetic parts when needed. Pins or screws to set and hold bones may be used. Sections of bone may be replaced with prosthetic rods or other parts. Sometime a plate is inserted to replace a damaged area of skull. Artificial hip replacement has become more common. Heart pacemakers or valves may be inserted. Many other types of prostheses are used.
- creation of a stoma, a permanent or semi-permanent opening in the body
- injury wound repair including cleaning and suturing injury wounds, setting broken bones, removal of foreign objects such as bullets, broken blades, etc.
- in transplant surgery, the donor organ (taken out of the donor's body) is inserted into the recipient's body and reconnected to the recipient in all necessary ways (blood vessels, ducts, etc.).
- arthrodesis - surgical connection of adjacent bones so the bones can grow together into one. Spinal fusion is an example of adjacent vertebrae connected allowing them to grow together into one piece.
- modifying the digestive tract in bariatric surgery for weight loss.
- repair of a fistula, hernia, or prolapse
- other problem corrections may include:
- clearing clogged ducts, blood or other vessels
- removal of calculi (stones)
- draining of accumulated fluids
- debridement- removal of dead, damaged, or diseased tissue
- Surgery may also involve reattachment of severed limbs, digits, or other body parts. Often a lot of microsurgery is involved in replantation. Muscles, blood vessels, and nerves often need to be reattached.
- Surgery has also been conducted to separate conjoined twins.
- Sex change operations are also a form of surgery.
Blood transfusions to the patient may be made to compensate for blood lost during surgery. Towards the end of surgery, sutures or staples are used to close the incision. Such closure allows the incision(s) to heal naturally. An incision scar typically remains. At the end of surgery when the patient is able to breath on one's own, the patient is taken off of mechanical ventilation and any endotracheal tube used is removed.
After completion of surgery, the patient is brought to a recovery room for a while and closely monitored. After some major operations, the patient may be in an intensive care unit (ICU) for a while. Afterwards a patient often continues recuperation in a regular hospital room or if surgery was relatively minor, discharged to recuperate at home. A patient having undergone surgery on the digestive system may be put on a liquid diet for a while. Often after surgery, the incision closure is checked periodically for signs of infection. External stitches are removed after perhaps 10 days or so (See Suture), after healing of the incision is well under way.
Adjuvant treatment such as chemotherapy, radiation therapy, or administration of medication such as anti-rejection medicine for transplants may be done. Other follow-up checks or rehabilitation may be done for a recovery period. As a result of some serious surgery, it is possible for a patient to suffer perioperative mortality, i.e. die during or after the surgery.
# History
At least two prehistoric cultures had developed forms of surgery. The oldest for which we have evidence is trepannation, in which a hole is drilled or scraped into the skull, thus exposing the dura mater in order to treat health problems related to intracranial pressure and other diseases. Evidence has been found in prehistoric human remains from Neolithic times, in cave paintings, and the procedure continued in use well into recorded history. Surprisingly, many prehistoric and premodern patients had signs of their skull structure healing; suggesting that many survived the operation. In modern-day Pakistan, remains from the early Harappan periods of the Indus Valley Civilization (c. 3300 BC) show evidence of teeth having been drilled dating back 9,000 years. A final candidate for prehistoric surgical techniques is ancient Egypt, where a mandible dated to approximately 2650 BC shows two perforations just below the root of the first molar, indicating the draining of an abscessed tooth. Recent excavations of the construction workers of the Egyptian pyramids also led to possible evidence of brain surgery.
The oldest known surgical texts date back to Indian physician Sushruta, the "Father of Surgery", who taught and practiced surgery on the banks of the Ganges around 600 BC. Much of what is known about Sushruta is contained in a series of volumes he authored, which are collectively known as the Susrutha Samhita. It is the oldest known surgical text and it describes in great detail the examination, diagnosis, treatment, and prognosis of numerous ailments, as well as procedures on performing various forms of plastic surgery, such as cosmetic surgery and rhinoplasty. His technique for the latter, used to reconstruct noses that were amputated as a punishment for crimes, is practiced almost unchanged in technique to this day.
Other ancient cultures to have surgical knowledge include ancient Greece - the Hippocratic Oath was an innovation of the Greek physician Hippocrates - and ancient China. However ancient Greek culture traditionally considered the practice of opening the body to be repulsive and thus left known surgical practices such as lithotomy to such persons as practice . In China, Hua Tuo was a famous Chinese physician during the Eastern Han and Three Kingdoms era. He was the first person to perform surgery with the aid of anesthesia, some 1600 years before the practice was adopted by Europeans.
In the Middle Ages, surgery was developed to a high degree in the Islamic world, with renowned practitioners such as Abulcasis (Abu al-Qasim Khalaf ibn al-Abbas Al-Zahrawi), an Andalusian-Arab physician and scientist who practised in the Zahra suburb of Córdoba. A great medieval surgeon, whose comprehensive medical texts shaped European surgical procedures up until the Renaissance. He is also often regarded as a Father Of Surgery.
In Europe, the demand grew for surgeons to formally study for many years before practicing; universities such as Montpellier, Padua and Bologna Universities were particularly renowned. By the fifteenth century at the latest, surgery had split away from physics as its own subject, of a lesser status than pure medicine, and initially took the form of a craft tradition until Rogerius Salernitanus composed his Chirurgia, laying the foundation for modern Western surgical manuals up to the modern time. Late in the nineteenth century, Bachelor of Surgery degrees (usually Ch.B.) began to be awarded with the (M.B.), and the mastership became a higher degree, usually abbreviated Ch.M. or M.S. in London, where the first degree was M.B.,B.S.
## Modern surgery
Modern surgery developed rapidly with the scientific era. Ambroise Paré (sometimes spelled "Ambrose") pioneered the treatment of gunshot wounds, and the first modern surgeons were battlefield doctors in the Napoleonic Wars. Naval surgeons were often barber surgeons, who combined surgery with their main jobs as barbers. Three main developments permitted the transition to modern surgical approaches - control of bleeding, control of infection and control of pain (anaesthesia).
# Conditions treated by surgery
Surgery is used to both as a treatment, and as an aspect of treatment, for many conditions, including:
- Physical trauma, e.g. wounds
- Anatomical Abnormalities
- Disorders of function
- Inflammation
- Ischaemia and infarction
- Metabolic disorders
- Neoplasia
- Other abnormalities of tissue growth, e.g. cysts, hyperplasia or Organ hypertrophy, as well as some cancers, if caught early enough
- Deformity and heavy scarring.
- Brain damage and nerve damage
# Common procedures
Five of the most common surgical procedures in the United States are male circumcision, obstetric: episiotomy, repair of obstetric laceration, cesarean section, and artificial rupture of the amniotic membrane
The most common non-obstetric surgical procedures include amputation, appendectomy, cataract surgery, circumcision, dental extraction and herniorraphy.
According to 1996 data from the US National Center for Health Statistics, 40.3 million inpatient surgical procedures were performed in the United States in 1996, followed closely by 31.5 million outpatient operations. | Surgery
Editor-In-Chief: Niral Shah, M.D. [1]
# Overview
In medicine, surgery (from the Greek [χειρουργική] error: {{lang}}: text has italic markup (help) and latin [chirurgiae] error: {{lang}}: text has italic markup (help) meaning "hand work") is a medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance, or sometimes for some other reason. An act of performing surgery may be called a surgical procedure, operation, or simply surgery. In this context, the verb operating means performing surgery. The adjective surgical means pertaining to surgery; e.g. surgical instruments or surgical nurse. The patient or subject that the surgery is being performed on can be a person or an animal. A surgeon is a person who performs surgery on patients. Persons described as surgeons are commonly medical practitioners, but the term is also applied to dentists and veterinarians. Surgery can last from minutes to hours, but is typically not an ongoing or periodic type of treatment.
The term surgery can also refer to the place where surgery is performed, or simply the office of a physician, dentist, or veterinarian.
# Overview of modern surgery
Although it is sometimes difficult to determine when a medical procedure is considered surgery, a medical treatment that involves a cutting of a patient's live tissue (e.g., hair and nails are dead tissue) is usually considered surgery of some sort. A medical procedure involving a drilling of live tissue in a body would often be considered surgery, but mere piercing of a body is not necessarily surgery since piercing is often done for taking samples or draining fluids from or injecting materials into the body, or setting up intravenous drip, and usually does not require suturing to close the pierced opening. Even if a medical procedure or treatment does not include cutting or drilling of live tissue in a body, it may be considered surgery, if it involves common surgical procedure or a setting, such as use of an operating room or table in a hospital, anesthesia, antiseptic conditions, typical surgical instruments, and suturing or stapling. Surgery is considered an invasive procedure. Examples of surgery without cutting the body may include debridement or closing (suturing or stapling) an open wound or applying skin grafts if done under typical surgical conditions. Many types of more complicated or involved surgery are obviously considered surgery, since they involve common surgical procedure or setting as mentioned above. A medical procedure may be surgery even if not all of the typical surgical conditions or procedures mentioned above are used.
## A few general types of surgery
Surgery can be categorized in many ways, a few of which are mentioned as follows. Some surgery may be required to save the life of a patient. Elective surgery is surgery not needed to save the life of the patient, but is expected to provide some other benefit. Emergency surgery is surgery which must be done quickly to save life, limb, or other capacity such as eyesight. Exploratory surgery is for investigating a patient's medical condition or making a diagnosis. Therapeutic surgery is for treating a patient. Surgery may start out as exploratory and become therapeutic. Amputation involves cutting off a body part; for example, a limb or digit. Replantation, an often difficult type of surgery more recently developed, involves reattaching a severed body part. Reconstructive surgery involves reconstruction of an injured, mutilated, or deformed part of the body. Reconstructive surgery is for reshaping of certain bodily tissues including bone, cartilage, muscle, fat, and skin that have been previously damanged by trauma or are congenitally abnormal.
Cosmetic surgery, a common type of elective surgery that is done to improve the appearance of the patient. Excision is the cutting out of an organ or other body part from the patient. Transplant surgery is the replacement of an organ or body part by insertion of another from different human (or animal) into the patient. Removing an organ or body part from a live human or animal for use in transplant is also a type of surgery. Minimally invasive surgery involves smaller outer incision(s) to insert some sort of endoscope, which is tube-like equipment, to perform surgery. There are also many types of more specific surgeries. Laser surgery involves use of a laser for cutting tissue instead of a scalpel or similar surgical instruments. Microsurgery is fine surgery with the aid of a microscope for the surgeon to see better. Bariatric surgery is a class of surgery for treating obesity, a common example of which is gastric bypass surgery. Surgery is also used for sterilization to prevent reproduction, although it is a rather simple procedure for males.
Suffixes used for some surgical procedures:
- Excision surgery names often start with a name for the organ to be excised (cut out) and end in -ectomy.
- Procedures involving cutting into an organ or tissue end in -otomy. A surgical procedure cutting through the abdominal wall to gain access to the abdominal cavity is a laparotomy.
- Minimally invasive procedures involving small incisions through which an endoscope is inserted end in -oscopy. For example, such surgery in the abdominal cavity is called laparoscopy.
- Procedures for formation of a permanent or semi-permanent opening called a stoma in the body end in -ostomy.
- Reconstruction or Cosmetic surgery of a body part starts with a name for the body part to be reconstructed and ends in -oplasty. Rhino is used as a prefix for "nose", so rhinoplasty is basically reconstructive or cosmetic surgery for the nose.
For specific examples, see List of surgical procedures.
## Description of surgical procedure
At a hospital, modern surgery is often done in an operating room using surgical instruments, an operating table for the patient, and other equipment. Any surgical instrument which go into the body must be pre-sterilized to avoid infection by micro-organisms. Also to maintain sanitation and sterility, surgeons clean (scrub) their hands. The surgical team wears sterile gloves during surgery. Surgical masks and gowns are also worn.
Modern surgery usually proceeds as follows:
Prior to surgery, particularly if it's non-emergency, the patient is given a medical examination, certain pre-operative tests, an ASA score, and (if satisfactory) a surgical clearance to be operated on. An autologous blood donation may be made a couple weeks prior to surgery to readd in case of blood loss during surgery. If the surgery involves the digestive system, evacuation of the digestive tract with subsequent fasting is done by the patient.
Other preparations for surgery are often done. When the patient enters the operating room, intravenous injection and various instruments to monitor the patient's vital signs are attached. The skin surface to be operated on is cleaned and prepared by shaving hair in area of incision and applying an antiseptic such as betadine to avoid a possibility of infection.
Anesthesia is administered to prevent pain from incision, other tissue cutting and suturing, etc. Although in theory it may sometimes be possible to operate without anesthesia, in most surgeries the pain would be unbearable and a patient would not hold sufficiently still for a surgeon to precisely operate. The anesthesia could be local or general anesthesia. With local anesthesia, the body area operated on is anesthetized, but the patient can remain conscious. With general anesthesia, the patient is rendered unconscious during surgery by an anesthesiologist. The anesthesia is often administered in the form of a drug. For certain serious types of surgery when a muscle relaxant is used, the patient undergoes intubation and is placed on mechanical ventilation using a mechanical ventilator. Intubation is inserting an endotracheal tube into the mouth, through the throat, and into the trachea to provide oxygen to the lungs. Open heart surgery often involves placement of a patient on a heart-lung machine and lowering body temperature so the heart stops beating. When finished, body temperature is raised and, if necessary, an electrical impulse administered to restart the heart.
Then, an incision is made to access the inside of the body area to be worked on. Blood vessels may be clamped to prevent bleeding. Other surgical tools (instruments) may be used to keep the incision open. It is commonly desired to keep the incision as small as possible. Various internal membranes may be cut also for further access inside. In certain cases, bone may be cut to further access the interior of the body; for example, cutting the skull for brain surgery or cutting the sternum for thoracic (chest) surgery to open up the rib cage.
Work to correct the problem in body then proceeds. This work may involve:
- excision - cutting out an organ, tumor, or other body part.
- resection - partial removal of an organ or other bodily structure.
- reconnection of organs, tissues, etc., particularly if severed. Resection of organs such as intestines involves reconnection. Internal suturing or stapling may be used. Surgical connection between blood vessels or other tubular or hollow structures such as loops of intestine is called anastomosis.
- ligation - tying off blood vessels, ducts, or "tubes".
- grafts - may be severed pieces of tissue cut from the same (or different) body or flaps of tissue still partly connected to the body but resewn for rearranging or restructuring of the area of the body in question. Although grafting is often used in cosmetic surgery, it is also used in other surgery. Grafts may be taken from one area of the patient's body and inserted to another area of the body. An example is bypass surgery, where clogged blood vessels are bypassed with a graft from another part of the body. Alternatively, grafts may be from other persons, cadavers, or animals.
- insertion of prosthetic parts when needed. Pins or screws to set and hold bones may be used. Sections of bone may be replaced with prosthetic rods or other parts. Sometime a plate is inserted to replace a damaged area of skull. Artificial hip replacement has become more common. Heart pacemakers or valves may be inserted. Many other types of prostheses are used.
- creation of a stoma, a permanent or semi-permanent opening in the body
- injury wound repair including cleaning and suturing injury wounds, setting broken bones, removal of foreign objects such as bullets, broken blades, etc.
- in transplant surgery, the donor organ (taken out of the donor's body) is inserted into the recipient's body and reconnected to the recipient in all necessary ways (blood vessels, ducts, etc.).
- arthrodesis - surgical connection of adjacent bones so the bones can grow together into one. Spinal fusion is an example of adjacent vertebrae connected allowing them to grow together into one piece.
- modifying the digestive tract in bariatric surgery for weight loss.
- repair of a fistula, hernia, or prolapse
- other problem corrections may include:
- clearing clogged ducts, blood or other vessels
- removal of calculi (stones)
- draining of accumulated fluids
- debridement- removal of dead, damaged, or diseased tissue
- Surgery may also involve reattachment of severed limbs, digits, or other body parts. Often a lot of microsurgery is involved in replantation. Muscles, blood vessels, and nerves often need to be reattached.
- Surgery has also been conducted to separate conjoined twins.
- Sex change operations are also a form of surgery.
Blood transfusions to the patient may be made to compensate for blood lost during surgery. Towards the end of surgery, sutures or staples are used to close the incision. Such closure allows the incision(s) to heal naturally. An incision scar typically remains. At the end of surgery when the patient is able to breath on one's own, the patient is taken off of mechanical ventilation and any endotracheal tube used is removed.
After completion of surgery, the patient is brought to a recovery room for a while and closely monitored. After some major operations, the patient may be in an intensive care unit (ICU) for a while. Afterwards a patient often continues recuperation in a regular hospital room or if surgery was relatively minor, discharged to recuperate at home. A patient having undergone surgery on the digestive system may be put on a liquid diet for a while. Often after surgery, the incision closure is checked periodically for signs of infection. External stitches are removed after perhaps 10 days or so (See Suture), after healing of the incision is well under way.
Adjuvant treatment such as chemotherapy, radiation therapy, or administration of medication such as anti-rejection medicine for transplants may be done. Other follow-up checks or rehabilitation may be done for a recovery period. As a result of some serious surgery, it is possible for a patient to suffer perioperative mortality, i.e. die during or after the surgery.
# History
At least two prehistoric cultures had developed forms of surgery. The oldest for which we have evidence is trepannation,[1] in which a hole is drilled or scraped into the skull, thus exposing the dura mater in order to treat health problems related to intracranial pressure and other diseases. Evidence has been found in prehistoric human remains from Neolithic times, in cave paintings, and the procedure continued in use well into recorded history. Surprisingly, many prehistoric and premodern patients had signs of their skull structure healing; suggesting that many survived the operation. In modern-day Pakistan, remains from the early Harappan periods of the Indus Valley Civilization (c. 3300 BC) show evidence of teeth having been drilled dating back 9,000 years.[2] A final candidate for prehistoric surgical techniques is ancient Egypt, where a mandible dated to approximately 2650 BC shows two perforations just below the root of the first molar, indicating the draining of an abscessed tooth. Recent excavations of the construction workers of the Egyptian pyramids also led to possible evidence of brain surgery.
The oldest known surgical texts date back to Indian physician Sushruta, the "Father of Surgery", who taught and practiced surgery on the banks of the Ganges around 600 BC. Much of what is known about Sushruta is contained in a series of volumes he authored, which are collectively known as the Susrutha Samhita. It is the oldest known surgical text and it describes in great detail the examination, diagnosis, treatment, and prognosis of numerous ailments, as well as procedures on performing various forms of plastic surgery, such as cosmetic surgery and rhinoplasty.[3] His technique for the latter, used to reconstruct noses that were amputated as a punishment for crimes, is practiced almost unchanged in technique to this day.
Other ancient cultures to have surgical knowledge include ancient Greece - the Hippocratic Oath was an innovation of the Greek physician Hippocrates - and ancient China. However ancient Greek culture traditionally considered the practice of opening the body to be repulsive and thus left known surgical practices such as lithotomy to such persons as practice [it]. In China, Hua Tuo was a famous Chinese physician during the Eastern Han and Three Kingdoms era. He was the first person to perform surgery with the aid of anesthesia, some 1600 years before the practice was adopted by Europeans.
In the Middle Ages, surgery was developed to a high degree in the Islamic world, with renowned practitioners such as Abulcasis (Abu al-Qasim Khalaf ibn al-Abbas Al-Zahrawi), an Andalusian-Arab physician and scientist who practised in the Zahra suburb of Córdoba. A great medieval surgeon, whose comprehensive medical texts shaped European surgical procedures up until the Renaissance. He is also often regarded as a Father Of Surgery.[4]
In Europe, the demand grew for surgeons to formally study for many years before practicing; universities such as Montpellier, Padua and Bologna Universities were particularly renowned. By the fifteenth century at the latest, surgery had split away from physics as its own subject, of a lesser status than pure medicine, and initially took the form of a craft tradition until Rogerius Salernitanus composed his Chirurgia, laying the foundation for modern Western surgical manuals up to the modern time. Late in the nineteenth century, Bachelor of Surgery degrees (usually Ch.B.) began to be awarded with the (M.B.), and the mastership became a higher degree, usually abbreviated Ch.M. or M.S. in London, where the first degree was M.B.,B.S.
## Modern surgery
Modern surgery developed rapidly with the scientific era. Ambroise Paré (sometimes spelled "Ambrose"[5]) pioneered the treatment of gunshot wounds, and the first modern surgeons were battlefield doctors in the Napoleonic Wars. Naval surgeons were often barber surgeons, who combined surgery with their main jobs as barbers. Three main developments permitted the transition to modern surgical approaches - control of bleeding, control of infection and control of pain (anaesthesia).
# Conditions treated by surgery
Surgery is used to both as a treatment, and as an aspect of treatment, for many conditions, including:
- Physical trauma, e.g. wounds
- Anatomical Abnormalities
- Disorders of function
- Inflammation
- Ischaemia and infarction
- Metabolic disorders
- Neoplasia
- Other abnormalities of tissue growth, e.g. cysts, hyperplasia or Organ hypertrophy, as well as some cancers, if caught early enough
- Deformity and heavy scarring.
- Brain damage and nerve damage
# Common procedures
Five of the most common surgical procedures in the United States are male circumcision, obstetric: episiotomy, repair of obstetric laceration, cesarean section, and artificial rupture of the amniotic membrane
The most common non-obstetric surgical procedures include amputation, appendectomy, cataract surgery, circumcision, dental extraction and herniorraphy.
According to 1996 data from the US National Center for Health Statistics, 40.3 million inpatient surgical procedures were performed in the United States in 1996, followed closely by 31.5 million outpatient operations. | https://www.wikidoc.org/index.php/Operations | |
1b3a8f36ec379d203f0110ac78a19daaa1cba180 | wikidoc | Opsonin | Opsonin
An opsonin is any molecule that acts as a binding enhancer for the process of phagocytosis, for example, by coating the negatively-charged molecules on the membrane.
# Mechanism
Both the membrane of a phagocytosing cell, as well as its target, have a negative charge (zeta-potential), making it difficult for the two cells to come close together. During the process of opsonization, antigens are bound by antibody and/or complement molecules. Phagocytic cells express receptors that bind opsonin molecules. These include the Fc receptors. With the antigen coated in these molecules, binding of the antigen to the phagocyte is greatly enhanced. Most phagocytic binding cannot occur without opsonization of the antigen.
Furthermore, opsonization of the antigen and subsequent binding to an activated phagocyte will cause increased expression of complement receptors on neighboring phagocytes.
# Examples
Examples of opsonin molecules include:
- antibodies: IgG and IgA
- components of the complement system: C3b, C4b, and iC3b
- Surfactant
- Mannose-binding lectin (initiates the formation of C3b)
The most important are IgG and C3b. | Opsonin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
An opsonin is any molecule that acts as a binding enhancer for the process of phagocytosis, for example, by coating the negatively-charged molecules on the membrane.
# Mechanism
Both the membrane of a phagocytosing cell, as well as its target, have a negative charge (zeta-potential), making it difficult for the two cells to come close together. During the process of opsonization, antigens are bound by antibody and/or complement molecules. Phagocytic cells express receptors that bind opsonin molecules. These include the Fc receptors. With the antigen coated in these molecules, binding of the antigen to the phagocyte is greatly enhanced. Most phagocytic binding cannot occur without opsonization of the antigen.
Furthermore, opsonization of the antigen and subsequent binding to an activated phagocyte will cause increased expression of complement receptors on neighboring phagocytes.
# Examples
Examples of opsonin molecules include:
- antibodies: IgG and IgA
- components of the complement system: C3b, C4b, and iC3b
- Surfactant
- Mannose-binding lectin (initiates the formation of C3b)
The most important are IgG and C3b.[1] | https://www.wikidoc.org/index.php/Opsonin | |
dfc9d8d8039b12ef701aac3ff32668103409711f | wikidoc | Oregano | Oregano
Oregano or Pot Marjoram (Origanum vulgare) is a species of Origanum, native to Europe, the Mediterranean region and southern and central Asia. It is a perennial herb, growing to 20-80 cm tall, with opposite leaves 1-4 cm long. The flowers are purple, 3-4 mm long, produced in erect spikes. Its name derives from the Greek origanon : oros “mountain” + the verb ganousthai “delight in”.
# Cultivation and uses
The subspecies of oregano Origanum vulgare hirtum is an important culinary herb. It is particularly widely used in Greek and Italian cuisines. It is the leaves that are used in cooking, and the dried herb is often more flavourful than the fresh.
Oregano is often used in tomato sauces, fried vegetables and grilled meat. Together with basil, it contributes much to the distinctive character of many Italian dishes.
Oregano combines nicely with pickled olives, capers and lovage leaves. Unlike most Italian herbs, oregano works with hot and spicy food, which is popular in southern Italy.
Oregano is an indispensable ingredient for Greek cuisine. Oregano adds flavour to the Greek salad and is usually used separately or added to the lemon-olive oil sauce that accompanies almost every fish or meat barbecues and some casseroles.
It has an aromatic, warm and slightly bitter taste. It varies in intensity; good quality is so strong that it almost numbs the tongue, but the cultivars adapted to colder climates have often unsatisfactory flavour. The influence of climate, season and soil on the composition of the essential oil is greater than the difference between the various species.
The related species Origanum onites (Greece, Asia Minor) and O. heracleoticum (Italy, Balkan peninsula, West Asia) have similar flavours. A closely related plant is marjoram from Asia Minor, which, however, differs significantly in taste, because phenolic compounds are missing in its essential oil. Some breeds show a flavour intermediate between oregano and marjoram.
The dish most associated with oregano is pizza. Its relatives have probably been eaten in Southern Italy for centuries.
## Health benefits
Oregano is high in antioxidant activity, due to a high content of phenolic acids and flavonoids (PMID 16218659, PMID 12730411). Additionally, oregano has demonstrated antimicrobial activity against food-borne pathogens such as Listeria monocytogenes (PMID 16218659). Both of these characteristics may be useful in both health and food preservation. In the Philippines, oregano (coleus aromaticus) is not commonly used for cooking but is rather considered as a primarily medicinal plant, useful for relieving children's coughs.
# Other plants called oregano
Mexican oregano, Lippia graveolens (Verbenaceae) is closely related to lemon verbena. It is a highly studied herb that is said to be of some medical use and is common in curandera female shamanic practices in Mexico and the Southwestern United States. Mexican oregano has a very similar flavour to oregano, but is usually stronger. It is becoming more commonly sold outside of Mexico, especially in the United States. It is
sometimes used as a substitute for epazote leaves; this substitution would not work the other way round.
Several other plants are also known as oregano in various parts of Mexico, including Poliomintha longiflora, Lippia berlandieri, and Plectranthus amboinicus (syn. Coleus aromaticus), also called Cuban oregano. | Oregano
Oregano or Pot Marjoram (Origanum vulgare) is a species of Origanum, native to Europe, the Mediterranean region and southern and central Asia. It is a perennial herb, growing to 20-80 cm tall, with opposite leaves 1-4 cm long. The flowers are purple, 3-4 mm long, produced in erect spikes. Its name derives from the Greek origanon [ὀρίγανον]: oros [ὄρος] “mountain” + the verb ganousthai [γανοῦσθαι] “delight in”.
# Cultivation and uses
The subspecies of oregano Origanum vulgare hirtum is an important culinary herb. It is particularly widely used in Greek and Italian cuisines. It is the leaves that are used in cooking, and the dried herb is often more flavourful than the fresh.[citation needed]
Oregano is often used in tomato sauces, fried vegetables and grilled meat. Together with basil, it contributes much to the distinctive character of many Italian dishes.
Oregano combines nicely with pickled olives, capers and lovage leaves. Unlike most Italian herbs,[citation needed] oregano works with hot and spicy food, which is popular in southern Italy.
Oregano is an indispensable ingredient for Greek cuisine. Oregano adds flavour to the Greek salad and is usually used separately or added to the lemon-olive oil sauce that accompanies almost every fish or meat barbecues and some casseroles.
It has an aromatic, warm and slightly bitter taste. It varies in intensity; good quality is so strong that it almost numbs the tongue, but the cultivars adapted to colder climates have often unsatisfactory flavour. The influence of climate, season and soil on the composition of the essential oil is greater than the difference between the various species.
The related species Origanum onites (Greece, Asia Minor) and O. heracleoticum (Italy, Balkan peninsula, West Asia) have similar flavours. A closely related plant is marjoram from Asia Minor, which, however, differs significantly in taste, because phenolic compounds are missing in its essential oil. Some breeds show a flavour intermediate between oregano and marjoram.
The dish most associated with oregano is pizza. Its relatives have probably been eaten in Southern Italy for centuries.
## Health benefits
Oregano is high in antioxidant activity, due to a high content of phenolic acids and flavonoids (PMID 16218659, PMID 12730411). Additionally, oregano has demonstrated antimicrobial activity against food-borne pathogens such as Listeria monocytogenes (PMID 16218659). Both of these characteristics may be useful in both health and food preservation. In the Philippines, oregano (coleus aromaticus) is not commonly used for cooking but is rather considered as a primarily medicinal plant, useful for relieving children's coughs.
# Other plants called oregano
Mexican oregano, Lippia graveolens (Verbenaceae) is closely related to lemon verbena. It is a highly studied herb that is said to be of some medical use and is common in curandera female shamanic practices in Mexico and the Southwestern United States. Mexican oregano has a very similar flavour to oregano, but is usually stronger. It is becoming more commonly sold outside of Mexico, especially in the United States. It is
sometimes used as a substitute for epazote leaves; this substitution would not work the other way round.
Several other plants are also known as oregano in various parts of Mexico, including Poliomintha longiflora, Lippia berlandieri, and Plectranthus amboinicus (syn. Coleus aromaticus), also called Cuban oregano. | https://www.wikidoc.org/index.php/Oregano | |
2a1e655d5a418c4be957971b40beb185851a796e | wikidoc | Solvent | Solvent
A solvent is a liquid or gas that dissolves a solid, liquid, or gaseous solute, resulting in a solution.
The most common solvent in everyday life is water. Most other commonly-used solvents are organic (carbon-containing) chemicals. These are called organic solvents. Solvents usually have a low boiling point and evaporate easily or can be removed by distillation, leaving the dissolved substance behind. To distinguish between solutes and solvents, solvents are usually present in the greater amount. Solvents can also be used to extract soluble compounds from a mixture, the most common example is the brewing of coffee or tea with hot water. Solvents are usually clear and colorless liquids and many have a characteristic odor. The concentration of a solution is the amount of compound that is dissolved in a certain volume of solvent. The solubility is the maximal amount of compound that is soluble in a certain volume of solvent at a specified temperature. Common uses for organic solvents are in dry cleaning (e.g. tetrachloroethylene), as paint thinners (e.g. toluene, turpentine), as nail polish removers and glue solvents (acetone, methyl acetate, ethyl acetate), in spot removers (e.g. hexane, petrol ether), in detergents (citrus terpenes), in perfumes (ethanol), and in chemical syntheses. The use of inorganic solvents (other than water) is typically limited to research chemistry and some technological processes.
# Solutions and solvation
When one substance is mixed with another, a solution is formed. The mixing is referred to as miscibility. However, in addition to mixing, both substances in the solution can interact with each other in specific ways. Solvation describes these interactions. When something is dissolved, molecules of the solvent arrange itself around molecules of the solute. Heat is evolved and entropy is decreased making the solution more thermodynamically stable than the solute alone. This arranging is mediated by the respective chemical properties of the solvent and solute, such as hydrogen bonding, dipole moment and polarizability.
# Solvent classifications
Solvents can be broadly classified into two categories polar/non-polar and protic/aprotic. Generally, the dielectric constant of the solvent provides a rough measure of a solvent's polarity. Solvents with a dielectric constant of less than 15 are generally considered nonpolar. Technically, the dielectric constant measures the solvent's ability to reduce the field strength of the electric field surrounding a charged particle immersed in it. This reduction is then compared to the field strength of the charged particle in a vacuum. In laymen's terms, dielectric constant of a solvent can be thought of as its ability to reduce the solute's internal charge.
## Other polarity scales
Dielectric constants are not the only measure of polarity. Because solvents are used by chemists to carry out chemical reactions or observe chemical and biological phenomena, more specific measures of polarity are required.
The Grunwald Winstein mY scale measures polarity in terms of solvent influence on buildup of positive charge of a solute during a chemical reaction.
Kosower's Z scale measures polarity in terms of the influence of the solvent on uv absorption maxima of a salt, usually pyridinium iodide or the pyridinium zwitterion.
Donor number and donar acceptor scale measures polarity in terms of how a solvent interacts with specific substances, like a strong Lewis acid or a strong Lewis base.
The polarity, dipole moment, polarizability and hydrogen bonding of a solvent determines what type of compounds it is able to dissolve and with what other solvents or liquid compounds it is miscible. As a rule of thumb, polar solvents dissolve polar compounds best and non-polar solvents dissolve non-polar compounds best: "like dissolves like". Strongly polar compounds like sugars (e.g. sucrose) or ionic compounds, like inorganic salts (e.g. table salt) dissolve only in very polar solvents like water, while strongly non-polar compounds like oils or waxes dissolve only in very non-polar organic solvents like hexane. Similarly, water and hexane (or vinegar and vegetable oil) are not miscible with each other and will quickly separate into two layers even after being shaken well.
## Polar protic and polar a-protic
Solvents with a relative static permittivity greater than 15 can be further divided into protic and aprotic. Protic solvents solvate anions (negatively charged solutes) strongly via hydrogen bonding. Water is a protic solvent. Aprotic solvents such as acetone or dichloromethane tend to have large dipole moments (separation of partial positive and partial negative charges within the same molecule) and solvate positively charged species via their negative dipole. In chemical reactions the use of polar protic solvents favors the SN1 reaction mechanism, while polar aprotic solvents favor the SN2 reaction mechanism.
# Solvent effects
## Boiling point
Another important property of solvents is boiling point. This also determines the speed of evaporation. Small amounts of low-boiling solvents like diethyl ether, dichloromethane, or acetone will evaporate in seconds at room temperature, while high-boiling solvents like water or dimethyl sulfoxide need higher temperatures, an air flow, or the application of vacuum for fast evaporation.
- Low Boilers: Boiling ranges below 100 °C
- Medium Boilers: Boiling ranges between 100 °C and 150 °C
- High Boilers: Boiling ranges above 150 °C
## Density
Most organic solvents have a lower density than water, which means they are lighter and will form a separate layer on top of water. An important exception: many halogenated solvents like dichloromethane or chloroform will sink to the bottom of a container, leaving water as the top layer. This is important to remember when partitioning compounds between solvents and water in a separatory funnel during chemical syntheses.
# Health and safety
## Fire
Most organic solvents are flammable or highly flammable, depending on their volatility. Exceptions are some chlorinated solvents like dichloromethane and chloroform. Mixtures of solvent vapors and air can explode. Solvent vapors are heavier than air, they will sink to the bottom and can travel large distances nearly undiluted. Solvent vapors can also be found in supposedly empty drums and cans, posing a flash fire hazard; hence empty containers of volatile solvents should be stored open and upside down.
Both diethyl ether and carbon disulfide have exceptionally low autoignition temperatures which increase greatly the fire risk associated with these solvents. The autoignition temperature of carbon disulfide is below 100°C (212°F), so as a result objects such as steam pipes, light bulbs, hotplates and recently extinguished bunsen burners are able to ignite its vapours.
## Peroxide formation
Ethers like diethyl ether and tetrahydrofuran (THF) can form highly explosive organic peroxides upon exposure to oxygen and light, THF is normally more able to form such peroxides than diethyl ether. One of the most susceptible solvents is diisopropyl ether.
The heteroatom (oxygen) stabilizes the formation of a free radical which is formed by the abstraction of a hydrogen atom by another free radical. The carbon centred free radical thus formed is able to react with an oxygen molecule to form a peroxide compound. A range of tests can be used to detect the presence of a peroxide in an ether, one is to use a combination of iron sulfate and potassium thiocyanate. The peroxide is able to oxidize the Fe2+ ion to an Fe3+ ion which then form a deep red coordination complex with the thiocyanate. In extreme cases the peroxides can form crystalline solids within the vessel of the ether.
Unless the desiccant used can destroy the peroxides, they will concentrate during distillation due to their higher boiling point. When sufficient peroxides have formed, they can form a crystalline and shock sensitive solid precipitate. When this solid is formed at the mouth of the bottle, turning the cap may provide sufficient energy for the peroxide to detonate. Peroxide formation is not a significant problem when solvents are used up quickly; they are more of a problem for laboratories which take years to finish a single bottle. Ethers have to be stored in the dark in closed canisters in the presence of stabilizers like butylated hydroxytoluene (BHT) or over sodium hydroxide.
Peroxides may be removed by washing with acidic iron(II) sulfate, filtering through alumina, or distilling from sodium/benzophenone. Alumina does not destroy the peroxides; it merely traps them. The advantage of using sodium/benzophenone is that moisture and oxygen is removed as well.
## Health effects
Many solvents can lead to a sudden loss of consciousness if inhaled in large amounts. Solvents like diethyl ether and chloroform have been used in medicine as anesthetics, sedatives, and hypnotics for a long time. Ethanol is a widely used and abused psychoactive drug. Diethyl ether, chloroform, and many other solvents (e.g. from gasoline or glues) are used recreationally in glue sniffing, often with harmful long term health effects like neurotoxicity or cancer. Methanol can cause internal damage to the eyes, including permanent blindness.
It is interesting to note that ethanol has a synergistic effect when taken in combination with many solvents. For instance a combination of toluene/benzene and ethanol causes greater nausea/vomiting than either substance alone. Many chemists make a point of not drinking beer/wine/other alcoholic drinks if they know that they have been exposed to an aromatic solvent.
## Environmental contamination
A major pathway to induce health effects arises from spills or leaks of solvents that reach the underlying soil. Since solvents readily migrate substantial distances, the creation of widespread soil contamination is not uncommon; there may be about 5000 sites worldwide that have major subsurface solvent contamination; this is particularly a health risk if aquifers are affected.
## Chronic health effects
Some solvents including chloroform and benzene (an ingredient of gasoline) are carcinogenic. Many others can damage internal organs like the liver, the kidneys, or the brain.
### General precautions
- Avoiding being exposed to solvent vapors by working in a fume hood, or with local exhaust ventilation (LEV), or in a well ventilated area
- Keeping the storage containers tightly closed
- Never using open flames near flammable solvents, use electrical heating instead
- Never flush flammable solvents down the drain, read safety data sheets for proper disposal information
- Avoiding the inhalation of solvent vapors
- Avoiding contact of the solvent with the skin — many solvents are easily absorbed through the skin. They also tend to dry the skin and may cause sores and wounds.
# Properties table of common solvents
The solvents are grouped into non-polar, polar aprotic, and polar protic solvents and ordered by increasing polarity. The polarity is given as the dielectric constant. The density of nonpolar solvents that are heavier than water is bolded. | Solvent
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A solvent is a liquid or gas that dissolves a solid, liquid, or gaseous solute, resulting in a solution.
The most common solvent in everyday life is water. Most other commonly-used solvents are organic (carbon-containing) chemicals. These are called organic solvents. Solvents usually have a low boiling point and evaporate easily or can be removed by distillation, leaving the dissolved substance behind. To distinguish between solutes and solvents, solvents are usually present in the greater amount. Solvents can also be used to extract soluble compounds from a mixture, the most common example is the brewing of coffee or tea with hot water. Solvents are usually clear and colorless liquids and many have a characteristic odor. The concentration of a solution is the amount of compound that is dissolved in a certain volume of solvent. The solubility is the maximal amount of compound that is soluble in a certain volume of solvent at a specified temperature. Common uses for organic solvents are in dry cleaning (e.g. tetrachloroethylene), as paint thinners (e.g. toluene, turpentine), as nail polish removers and glue solvents (acetone, methyl acetate, ethyl acetate), in spot removers (e.g. hexane, petrol ether), in detergents (citrus terpenes), in perfumes (ethanol), and in chemical syntheses. The use of inorganic solvents (other than water) is typically limited to research chemistry and some technological processes.
# Solutions and solvation
When one substance is mixed with another, a solution is formed.[1] The mixing is referred to as miscibility. However, in addition to mixing, both substances in the solution can interact with each other in specific ways. Solvation describes these interactions. When something is dissolved, molecules of the solvent arrange itself around molecules of the solute. Heat is evolved and entropy is decreased making the solution more thermodynamically stable than the solute alone. This arranging is mediated by the respective chemical properties of the solvent and solute, such as hydrogen bonding, dipole moment and polarizability.[2]
# Solvent classifications
Solvents can be broadly classified into two categories polar/non-polar and protic/aprotic. Generally, the dielectric constant of the solvent provides a rough measure of a solvent's polarity. Solvents with a dielectric constant of less than 15 are generally considered nonpolar.[3] Technically, the dielectric constant measures the solvent's ability to reduce the field strength of the electric field surrounding a charged particle immersed in it. This reduction is then compared to the field strength of the charged particle in a vacuum.[4] In laymen's terms, dielectric constant of a solvent can be thought of as its ability to reduce the solute's internal charge.
## Other polarity scales
Dielectric constants are not the only measure of polarity. Because solvents are used by chemists to carry out chemical reactions or observe chemical and biological phenomena, more specific measures of polarity are required.
The Grunwald Winstein mY scale measures polarity in terms of solvent influence on buildup of positive charge of a solute during a chemical reaction.
Kosower's Z scale measures polarity in terms of the influence of the solvent on uv absorption maxima of a salt, usually pyridinium iodide or the pyridinium zwitterion.[5]
Donor number and donar acceptor scale measures polarity in terms of how a solvent interacts with specific substances, like a strong Lewis acid or a strong Lewis base.[6]
The polarity, dipole moment, polarizability and hydrogen bonding of a solvent determines what type of compounds it is able to dissolve and with what other solvents or liquid compounds it is miscible. As a rule of thumb, polar solvents dissolve polar compounds best and non-polar solvents dissolve non-polar compounds best: "like dissolves like". Strongly polar compounds like sugars (e.g. sucrose) or ionic compounds, like inorganic salts (e.g. table salt) dissolve only in very polar solvents like water, while strongly non-polar compounds like oils or waxes dissolve only in very non-polar organic solvents like hexane. Similarly, water and hexane (or vinegar and vegetable oil) are not miscible with each other and will quickly separate into two layers even after being shaken well.
## Polar protic and polar a-protic
Solvents with a relative static permittivity greater than 15 can be further divided into protic and aprotic. Protic solvents solvate anions (negatively charged solutes) strongly via hydrogen bonding. Water is a protic solvent. Aprotic solvents such as acetone or dichloromethane tend to have large dipole moments (separation of partial positive and partial negative charges within the same molecule) and solvate positively charged species via their negative dipole.[7] In chemical reactions the use of polar protic solvents favors the SN1 reaction mechanism, while polar aprotic solvents favor the SN2 reaction mechanism.
# Solvent effects
## Boiling point
Another important property of solvents is boiling point. This also determines the speed of evaporation. Small amounts of low-boiling solvents like diethyl ether, dichloromethane, or acetone will evaporate in seconds at room temperature, while high-boiling solvents like water or dimethyl sulfoxide need higher temperatures, an air flow, or the application of vacuum for fast evaporation.
- Low Boilers: Boiling ranges below 100 °C
- Medium Boilers: Boiling ranges between 100 °C and 150 °C
- High Boilers: Boiling ranges above 150 °C
## Density
Most organic solvents have a lower density than water, which means they are lighter and will form a separate layer on top of water. An important exception: many halogenated solvents like dichloromethane or chloroform will sink to the bottom of a container, leaving water as the top layer. This is important to remember when partitioning compounds between solvents and water in a separatory funnel during chemical syntheses.
# Health and safety
## Fire
Most organic solvents are flammable or highly flammable, depending on their volatility. Exceptions are some chlorinated solvents like dichloromethane and chloroform. Mixtures of solvent vapors and air can explode. Solvent vapors are heavier than air, they will sink to the bottom and can travel large distances nearly undiluted. Solvent vapors can also be found in supposedly empty drums and cans, posing a flash fire hazard; hence empty containers of volatile solvents should be stored open and upside down.
Both diethyl ether and carbon disulfide have exceptionally low autoignition temperatures which increase greatly the fire risk associated with these solvents. The autoignition temperature of carbon disulfide is below 100°C (212°F), so as a result objects such as steam pipes, light bulbs, hotplates and recently extinguished bunsen burners are able to ignite its vapours.
## Peroxide formation
Ethers like diethyl ether and tetrahydrofuran (THF) can form highly explosive organic peroxides upon exposure to oxygen and light, THF is normally more able to form such peroxides than diethyl ether. One of the most susceptible solvents is diisopropyl ether.
The heteroatom (oxygen) stabilizes the formation of a free radical which is formed by the abstraction of a hydrogen atom by another free radical. The carbon centred free radical thus formed is able to react with an oxygen molecule to form a peroxide compound. A range of tests can be used to detect the presence of a peroxide in an ether, one is to use a combination of iron sulfate and potassium thiocyanate. The peroxide is able to oxidize the Fe2+ ion to an Fe3+ ion which then form a deep red coordination complex with the thiocyanate. In extreme cases the peroxides can form crystalline solids within the vessel of the ether.
Unless the desiccant used can destroy the peroxides, they will concentrate during distillation due to their higher boiling point. When sufficient peroxides have formed, they can form a crystalline and shock sensitive solid precipitate. When this solid is formed at the mouth of the bottle, turning the cap may provide sufficient energy for the peroxide to detonate. Peroxide formation is not a significant problem when solvents are used up quickly; they are more of a problem for laboratories which take years to finish a single bottle. Ethers have to be stored in the dark in closed canisters in the presence of stabilizers like butylated hydroxytoluene (BHT) or over sodium hydroxide.
Peroxides may be removed by washing with acidic iron(II) sulfate, filtering through alumina, or distilling from sodium/benzophenone. Alumina does not destroy the peroxides; it merely traps them. The advantage of using sodium/benzophenone is that moisture and oxygen is removed as well.
## Health effects
Many solvents can lead to a sudden loss of consciousness if inhaled in large amounts. Solvents like diethyl ether and chloroform have been used in medicine as anesthetics, sedatives, and hypnotics for a long time. Ethanol is a widely used and abused psychoactive drug. Diethyl ether, chloroform, and many other solvents (e.g. from gasoline or glues) are used recreationally in glue sniffing, often with harmful long term health effects like neurotoxicity or cancer. Methanol can cause internal damage to the eyes, including permanent blindness.
It is interesting to note that ethanol has a synergistic effect when taken in combination with many solvents. For instance a combination of toluene/benzene and ethanol causes greater nausea/vomiting than either substance alone. Many chemists make a point of not drinking beer/wine/other alcoholic drinks if they know that they have been exposed to an aromatic solvent.
## Environmental contamination
A major pathway to induce health effects arises from spills or leaks of solvents that reach the underlying soil. Since solvents readily migrate substantial distances, the creation of widespread soil contamination is not uncommon; there may be about 5000 sites worldwide that have major subsurface solvent contamination; this is particularly a health risk if aquifers are affected.
## Chronic health effects
Some solvents including chloroform and benzene (an ingredient of gasoline) are carcinogenic. Many others can damage internal organs like the liver, the kidneys, or the brain.
### General precautions
- Avoiding being exposed to solvent vapors by working in a fume hood, or with local exhaust ventilation (LEV), or in a well ventilated area
- Keeping the storage containers tightly closed
- Never using open flames near flammable solvents, use electrical heating instead
- Never flush flammable solvents down the drain, read safety data sheets for proper disposal information
- Avoiding the inhalation of solvent vapors
- Avoiding contact of the solvent with the skin — many solvents are easily absorbed through the skin. They also tend to dry the skin and may cause sores and wounds.
# Properties table of common solvents
The solvents are grouped into non-polar, polar aprotic, and polar protic solvents and ordered by increasing polarity. The polarity is given as the dielectric constant. The density of nonpolar solvents that are heavier than water is bolded. | https://www.wikidoc.org/index.php/Organic_solvent | |
2bc311e574d3e1ea4f29a150a22eea0d3bec3cdb | wikidoc | Pharynx | Pharynx
# Overview
The pharynx (plural: pharynges) is an organ found in vertebrates and invertebrates, though the structure is not universally the same across the species. In humans the pharynx is part of the digestive system and also of the conducting zone of the respiratory system. (The conducting zone also includes the nose, larynx, trachea, bronchi, and bronchioles, and their function is to filter, warm, and moisten air and conduct it into the lungs.) The pharynx makes up the part of the throat situated immediately posterior to the nasal cavity, posterior to the mouth and superior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx, the oropharynx and the laryngopharynx. It is also important in vocalization.
There are two sets of pharyngeal muscles that act upon the pharynx. These are arranged as an inner layer of longitudinal muscles and an outer circular layer.
# Structure
## Nasopharynx
The upper portion of the pharynx, the nasopharynx, extends from the base of the skull to the upper surface of the soft palate. It includes the space between the internal nares and the soft palate and lies above the oral cavity. The adenoids, also known as the pharyngeal tonsils, are lymphoid tissue structures located in the posterior wall of the nasopharynx. Waldeyer's tonsillar ring is an annular arrangement of lymphoid tissue in both the nasopharynx and oropharynx.
Polyps or mucus can obstruct the nasopharynx, as can congestion due to an upper respiratory infection. The eustachian tubes, which connect the middle ear to the pharynx, open into the nasopharynx. The opening and closing of the eustachian tubes serves to equalize the barometric pressure in the middle ear with that of the ambient atmosphere.
The anterior aspect of the nasopharynx communicates through the choanae with the nasal cavities. On its lateral walls are the pharyngeal ostia of the auditory tube, somewhat triangular in shape, and bounded behind by a firm prominence, the torus tubarius or cushion, caused by the medial end of the cartilage of the tube that elevates the mucous membrane. Two folds arise from the cartilaginous opening:
- the salpingopharyngeal fold, a vertical fold of mucous membrane extending from the inferior part of the torus and containing the salpingopharyngeus muscle
- the salpingopalatine fold, a smaller fold extending from the superior part of the torus to the palate and containing the levator veli palatini muscle. The tensor veli palatini is lateral to the levator and does not contribute the fold, since the origin is deep to the cartilaginous opening.
Behind the opening of the auditory tube is a deep recess, the pharyngeal recess (also referred to as the fossa of Rosenmüller). On the posterior wall is a prominence, best marked in childhood, produced by a mass of lymphoid tissue, which is known as the pharyngeal tonsil. Superior to the pharyngeal tonsil, in the midline, an irregular flask-shaped depression of the mucous membrane sometimes extends up as far as the basilar process of the occipital bone, this is known as the pharyngeal bursa.
## Oropharynx
The oropharynx lies behind the oral cavity, extending from the uvula to the level of the hyoid bone. It opens anteriorly, through the isthmus faucium, into the mouth, while in its lateral wall, between the palatoglossal arch and the palatopharyngeal arch, is the palatine tonsil. The anterior wall consists of the base of the tongue and the epiglottic vallecula; the lateral wall is made up of the tonsil, tonsillar fossa, and tonsillar (faucial) pillars; the superior wall consists of the inferior surface of the soft palate and the uvula. Because both food and air pass through the pharynx, a flap of connective tissue called the epiglottis closes over the glottis when food is swallowed to prevent aspiration. The oropharynx is lined by non-keratinised squamous stratified epithelium.
The HACEK organisms (Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella) are part of the normal oropharyngeal flora, which grow slowly, prefer a carbon dioxide-enriched atmosphere, and share an enhanced capacity to produce endocardial infections, especially in young children. Fusobacterium is a pathogen.
## Laryngopharynx
The laryngopharynx, (Latin: pars laryngea pharyngis), also known as hypopharynx, is the caudal part of the pharynx; it is the part of the throat that connects to the esophagus. It lies inferior to the epiglottis and extends to the location where this common pathway diverges into the respiratory (larynx) and digestive (esophagus) pathways. At that point, the laryngopharynx is continuous with the esophagus posteriorly. The esophagus conducts food and fluids to the stomach; air enters the larynx anteriorly. During swallowing, food has the "right of way", and air passage temporarily stops. Corresponding roughly to the area located between the 4th and 6th cervical vertebrae, the superior boundary of the laryngopharynx is at the level of the hyoid bone. The laryngopharynx includes three major sites: the pyriform sinus, postcricoid area, and the posterior pharyngeal wall. Like the oropharynx above it, the laryngopharynx serves as a passageway for food and air and is lined with a stratified squamous epithelium. It is innervated by the pharyngeal plexus.
The vascular supply to the laryngopharynx includes the superior thyroid artery, the lingual artery and the ascending pharyngeal artery. The primary neural supply is from both the vagus and glossopharyngeal nerves. The vagus nerve provides a branch termed "Arnolds Nerve" which also supplies the external auditory canal, thus laryngopharyngeal cancer can result in referred otalgia. This nerve is also responsible for the ear-cough reflex in which stimulation of the ear canal results in a person coughing.
# Clinical significance
## Inflammation
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is painful, and thus is often referred to as a sore throat. Inflammation of the tonsils (tonsillitis) and/or larynx (laryngitis) may occur simultaneously, which can make eating difficult or painful.
Most cases are caused by virus|viral infections (40%-60%), with the remainder caused by bacterial infections, fungus|fungal infections, or irritants such as pollutants or chemical substances.
Treatment of viral causes are mainly symptomatic while bacterial or fungal causes may be amenable to antibiotics and antifungals respectively.
## Pharyngeal cancer
Neck squamous cell carcinoma, an oropharyngeal cancer, occurs in humans.
# History
## Etymology
The word pharynx (pronounced /ˈfærɪŋks/) is derived from the Greek φάρυγξ phárynx, meaning "throat". Its plural form is pharynges /fəˈrɪndʒiːz/ or pharynxes /ˈfærɪŋksəz/, and its adjective form is pharyngeal (/ˌfærɪnˈdʒiːəl/ or /fəˈrɪndʒiəl/).
# Other animals
## Vertebrates
All vertebrates have a pharynx, used in both feeding and respiration. The pharynx arises during development in all vertebrates through a series of six or more outpocketings on the lateral sides of the head. These outpocketings are pharyngeal arches, and they give rise to a number of different structures in the skeletal, muscular and circulatory systems. The structure of the pharynx varies across the vertebrates. It differs in dogs, horses and ruminants. In dogs a single duct connects the nasopharynx to the nasal cavity. The tonsils are a compact mass which point away from the lumen of the pharynx.
In the horse the auditory tube opens into the guttural pouch and the tonsils are diffuse and raised slightly. Horses are unable to breathe through the mouth as the free apex of the rostral epiglottis lies dorsal to the soft palate in a normal horse. In ruminants the tonsils are a compact mass which point towards the lumen of the pharynx.
Pharyngeal arches are characteristic features of vertebrates whose origin can be traced back through chordates to basal deuterostomes who also share endodermal outpocketings of the pharyngeal apparatus. Similar patterns of gene expression can be detected in the developing pharynx of amphioxus and hemichordates. However, the vertebrate pharynx is unique in that it gives rise to endoskeletal support through the contribution of neural crest cells.
Pharyngeal jaws are a "second set" of jaws contained within the pharynx of many species of fish, distinct from the primary (oral) jaws. Pharyngeal jaws have been studied in moray eels where their specific action is noted. When the moray bites prey, it first bites normally with its oral jaws, capturing the prey. Immediately thereafter, the pharyngeal jaws are brought forward and bite down on the prey to grip it; they then retract, pulling the prey down the eel's esophagus, allowing it to be swallowed.
## Invertebrates
Invertebrates also have a pharynx. Invertebrates with a pharynx include the tardigrades,annelids and arthropods, and the priapulids (which have an eversible pharynx).
The term "pharynx" is used loosely across the animal kingdom for the portion of the digestive tract loosely analogous to the vertebrate pharynx, but this need not imply deep structural or developmental similarities, or that the structures are homologous.
The "pharynx" of the nematode worm is a muscular food pump in the head, triangular in cross-section, that grinds food and transports it directly to the intestines. A one-way valve connects the pharynx to the excretory canal.
# Additional images
- Conducting passages
Conducting passages
- Organs of the digestive system
- Nose and nasal
- Coronal section of right ear, showing auditory tube and levator veli palatini muscle.
- The entrance to the larynx, viewed from behind
- The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind.
- Deep dissection of human larynx, pharynx and tongue seen from behind
- The nasopharynx, oropharynx, and laryngopharynx or larynx can be seen clearly in this sagittal section of the head and neck. | Pharynx
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The pharynx (plural: pharynges) is an organ found in vertebrates and invertebrates, though the structure is not universally the same across the species. In humans the pharynx is part of the digestive system and also of the conducting zone of the respiratory system. (The conducting zone also includes the nose, larynx, trachea, bronchi, and bronchioles, and their function is to filter, warm, and moisten air and conduct it into the lungs.[1]) The pharynx makes up the part of the throat situated immediately posterior to the nasal cavity, posterior to the mouth and superior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx, the oropharynx and the laryngopharynx. It is also important in vocalization.
There are two sets of pharyngeal muscles that act upon the pharynx. These are arranged as an inner layer of longitudinal muscles and an outer circular layer.
# Structure
## Nasopharynx
The upper portion of the pharynx, the nasopharynx, extends from the base of the skull to the upper surface of the soft palate.[2] It includes the space between the internal nares and the soft palate and lies above the oral cavity. The adenoids, also known as the pharyngeal tonsils, are lymphoid tissue structures located in the posterior wall of the nasopharynx. Waldeyer's tonsillar ring is an annular arrangement of lymphoid tissue in both the nasopharynx and oropharynx.
Polyps or mucus can obstruct the nasopharynx, as can congestion due to an upper respiratory infection. The eustachian tubes, which connect the middle ear to the pharynx, open into the nasopharynx. The opening and closing of the eustachian tubes serves to equalize the barometric pressure in the middle ear with that of the ambient atmosphere.
The anterior aspect of the nasopharynx communicates through the choanae with the nasal cavities. On its lateral walls are the pharyngeal ostia of the auditory tube, somewhat triangular in shape, and bounded behind by a firm prominence, the torus tubarius or cushion, caused by the medial end of the cartilage of the tube that elevates the mucous membrane. Two folds arise from the cartilaginous opening:
- the salpingopharyngeal fold, a vertical fold of mucous membrane extending from the inferior part of the torus and containing the salpingopharyngeus muscle
- the salpingopalatine fold, a smaller fold extending from the superior part of the torus to the palate and containing the levator veli palatini muscle. The tensor veli palatini is lateral to the levator and does not contribute the fold, since the origin is deep to the cartilaginous opening.
Behind the opening of the auditory tube is a deep recess, the pharyngeal recess (also referred to as the fossa of Rosenmüller). On the posterior wall is a prominence, best marked in childhood, produced by a mass of lymphoid tissue, which is known as the pharyngeal tonsil. Superior to the pharyngeal tonsil, in the midline, an irregular flask-shaped depression of the mucous membrane sometimes extends up as far as the basilar process of the occipital bone, this is known as the pharyngeal bursa.
## Oropharynx
The oropharynx lies behind the oral cavity, extending from the uvula to the level of the hyoid bone. It opens anteriorly, through the isthmus faucium, into the mouth, while in its lateral wall, between the palatoglossal arch and the palatopharyngeal arch, is the palatine tonsil.[3] The anterior wall consists of the base of the tongue and the epiglottic vallecula; the lateral wall is made up of the tonsil, tonsillar fossa, and tonsillar (faucial) pillars; the superior wall consists of the inferior surface of the soft palate and the uvula. Because both food and air pass through the pharynx, a flap of connective tissue called the epiglottis closes over the glottis when food is swallowed to prevent aspiration. The oropharynx is lined by non-keratinised squamous stratified epithelium.
The HACEK organisms (Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella) are part of the normal oropharyngeal flora, which grow slowly, prefer a carbon dioxide-enriched atmosphere, and share an enhanced capacity to produce endocardial infections, especially in young children.[4] Fusobacterium is a pathogen.[5]
## Laryngopharynx
The laryngopharynx, (Latin: pars laryngea pharyngis), also known as hypopharynx, is the caudal part of the pharynx; it is the part of the throat that connects to the esophagus. It lies inferior to the epiglottis and extends to the location where this common pathway diverges into the respiratory (larynx) and digestive (esophagus) pathways. At that point, the laryngopharynx is continuous with the esophagus posteriorly. The esophagus conducts food and fluids to the stomach; air enters the larynx anteriorly. During swallowing, food has the "right of way", and air passage temporarily stops. Corresponding roughly to the area located between the 4th and 6th cervical vertebrae, the superior boundary of the laryngopharynx is at the level of the hyoid bone. The laryngopharynx includes three major sites: the pyriform sinus, postcricoid area, and the posterior pharyngeal wall. Like the oropharynx above it, the laryngopharynx serves as a passageway for food and air and is lined with a stratified squamous epithelium. It is innervated by the pharyngeal plexus.
The vascular supply to the laryngopharynx includes the superior thyroid artery, the lingual artery and the ascending pharyngeal artery. The primary neural supply is from both the vagus and glossopharyngeal nerves. The vagus nerve provides a branch termed "Arnolds Nerve" which also supplies the external auditory canal, thus laryngopharyngeal cancer can result in referred otalgia. This nerve is also responsible for the ear-cough reflex in which stimulation of the ear canal results in a person coughing.
# Clinical significance
## Inflammation
Pharyngitis is an inflammation of the throat or pharynx.[6] In most cases it is painful, and thus is often referred to as a sore throat. Inflammation of the tonsils (tonsillitis) and/or larynx (laryngitis) may occur simultaneously, which can make eating difficult or painful.
Most cases are caused by virus|viral infections (40%-60%), with the remainder caused by bacterial infections, fungus|fungal infections, or irritants such as pollutants or chemical substances.[7]
Treatment of viral causes are mainly symptomatic while bacterial or fungal causes may be amenable to antibiotics and antifungals respectively.
## Pharyngeal cancer
Neck squamous cell carcinoma, an oropharyngeal cancer, occurs in humans.[8]
# History
## Etymology
The word pharynx (pronounced /ˈfærɪŋks/[9][10]) is derived from the Greek φάρυγξ phárynx, meaning "throat". Its plural form is pharynges /fəˈrɪndʒiːz/ or pharynxes /ˈfærɪŋksəz/, and its adjective form is pharyngeal (/ˌfærɪnˈdʒiːəl/ or /fəˈrɪndʒiəl/).
# Other animals
## Vertebrates
All vertebrates have a pharynx, used in both feeding and respiration. The pharynx arises during development in all vertebrates through a series of six or more outpocketings on the lateral sides of the head. These outpocketings are pharyngeal arches, and they give rise to a number of different structures in the skeletal, muscular and circulatory systems. The structure of the pharynx varies across the vertebrates. It differs in dogs, horses and ruminants. In dogs a single duct connects the nasopharynx to the nasal cavity. The tonsils are a compact mass which point away from the lumen of the pharynx.
In the horse the auditory tube opens into the guttural pouch and the tonsils are diffuse and raised slightly. Horses are unable to breathe through the mouth as the free apex of the rostral epiglottis lies dorsal to the soft palate in a normal horse. In ruminants the tonsils are a compact mass which point towards the lumen of the pharynx.
Pharyngeal arches are characteristic features of vertebrates whose origin can be traced back through chordates to basal deuterostomes who also share endodermal outpocketings of the pharyngeal apparatus. Similar patterns of gene expression can be detected in the developing pharynx of amphioxus and hemichordates. However, the vertebrate pharynx is unique in that it gives rise to endoskeletal support through the contribution of neural crest cells.[11]
Pharyngeal jaws are a "second set" of jaws contained within the pharynx of many species of fish, distinct from the primary (oral) jaws. Pharyngeal jaws have been studied in moray eels where their specific action is noted. When the moray bites prey, it first bites normally with its oral jaws, capturing the prey. Immediately thereafter, the pharyngeal jaws are brought forward and bite down on the prey to grip it; they then retract, pulling the prey down the eel's esophagus, allowing it to be swallowed.[12]
## Invertebrates
Invertebrates also have a pharynx. Invertebrates with a pharynx include the tardigrades,[13]annelids and arthropods,[14] and the priapulids (which have an eversible pharynx).[15]
The term "pharynx" is used loosely across the animal kingdom for the portion of the digestive tract loosely analogous to the vertebrate pharynx, but this need not imply deep structural or developmental similarities, or that the structures are homologous.[citation needed]
The "pharynx" of the nematode worm is a muscular food pump in the head, triangular in cross-section, that grinds food and transports it directly to the intestines. A one-way valve connects the pharynx to the excretory canal.
# Additional images
- Conducting passages
Conducting passages
- Organs of the digestive system
- Nose and nasal
- Coronal section of right ear, showing auditory tube and levator veli palatini muscle.
- The entrance to the larynx, viewed from behind
- The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind.
- Deep dissection of human larynx, pharynx and tongue seen from behind
- The nasopharynx, oropharynx, and laryngopharynx or larynx can be seen clearly in this sagittal section of the head and neck. | https://www.wikidoc.org/index.php/Oropharyngeal | |
a73726c0823364239219eb310e6440d02125ba99 | wikidoc | Osmosis | Osmosis
Osmosis is the spontaneous net movement of water across a semipermeable membrane from a region of low solute concentration to a solution with a high solute concentration, down a solute concentration gradient. It is a physical process in which a solvent moves, without input of energy, across a semi permeable membrane (permeable to the solvent, but not the solute) separating two solutions of different concentrations. Osmosis releases energy, and can be made to do work, as when a growing tree-root splits a stone.
Net movement of solvent is from the less-concentrated (hypotonic) to the more-concentrated (hypertonic) solution, which tends to reduce the difference in concentrations. This effect can be countered by increasing the pressure of the hypertonic solution, with respect to the hypotonic. The osmotic pressure is defined to be the pressure required to maintain an equilibrium, with no net movement of solvent. Osmotic pressure is a colligative property, meaning that the property depends on the molar concentration of the solute but not on its identity. Osmosis is the result of diffusion across a semi-permeable membrane.
Osmosis is important in biological systems as many biological membranes are semipermeable. In general, these membranes are impermeable to organic solutes with large molecules, such as polysaccharides, while permeable to water and small, uncharged solutes. Permeability may depend on solubility properties, charge, or chemistry as well as solute size. Water molecules travel through the plasma cell membrane, tonoplast (vacuole) or protoplast in two ways. Either by diffusing across the phospholipid bilayer directly, or via aquaporins (small transmembrane proteins similar to those in facilitated diffusion and in creating ion channels). Osmosis provides the primary means by which water is transported into and out of cells. The turgor pressure of a cell is largely maintained by osmosis, across the cell membrane, between the cell interior and its relatively hypotonic environment.
# Basic explanation
Consider a permeable membrane, such as visking tubing, with apertures big enough to allow water (solvent) molecules, but not larger solute molecules, to pass through. When this membrane is immersed in liquid it is constantly hit by molecules of the liquid, in motion due to their thermal kinetic energy. In this respect solute and solvent molecules are indistinguishable. At a molecular scale, every time a molecule hits the membrane it has a defined likelihood of passing through. Here, there is a difference: for water molecules this probability is non-zero; for solute molecules it is zero.
Suppose the membrane is in a volume of pure water. In this case, since the circumstances on both sides of the membrane are equivalent, water molecules pass in each direction at the same rate; there is no net flow of water through the membrane.
If there is a solution on one side, and pure water on the other, the membrane is still hit by molecules from both sides at the same rate. However, some of the molecules hitting the membrane from the solution side will be solute molecules, and these will not pass through the membrane. So water molecules pass through the membrane from this side at a slower rate. This will result in a net flow of water to the side with the solution. Assuming the membrane does not break, this net flow will slow and finally stop as the pressure on the solution side becomes such that the movement in each direction is equal: dynamic equilibrium. This could either be due to the water potential on both sides of the membrane being the same, or due to osmosis being inhibited by factors such as pressure potential or Osmotic pressure.
Osmosis can also be explained via the notion of entropy, from statistical mechanics. As above, suppose a permeable membrane separates equal amounts of pure solvent and a solution. Since a solution possesses more entropy than pure solvent, the second law of thermodynamics states that solvent molecules will flow into the solution until the entropy of the combined system is maximized. Notice that, as this happens, the solvent loses entropy while the solution gains entropy. Equilibrium, hence maximum entropy, is achieved when the entropy gradient becomes zero.
# Examples of osmosis
Osmotic pressure is the main cause of support in many plants. The osmotic entry of water raises the turgor pressure exerted against the cell wall, until it equals the osmotic pressure, creating a steady state.
When a plant cell is placed in a hypertonic solution, the water in the cells moves to an area higher in solute concentration, and the cell shrinks and so becomes flaccid. (This means the cell has become plasmolysed - the cell membrane has completely left the cell wall due to lack of water pressure on it; the opposite of turgid.)
Also, osmosis is responsible for the ability of plant roots to suck up water from the soil. Since there are many fine roots, they have a large surface area, water enters the roots by osmosis.
Osmosis can also be seen very effectively when potato slices are added to a high concentration of salt solution. The water from inside the potato moves to the salt solution, causing the potato to shrink and to lose its 'turgor pressure'. The more concentrated the salt solution, the bigger the difference in size and weight of the potato slice.
In unusual environments, osmosis can be very harmful to organisms. For example, freshwater and saltwater aquarium fish placed in water of a different salinity than that they are adapted to will die quickly, and in the case of saltwater fish, rather dramatically. Another example of a harmful osmotic effect is the use of table salt to kill leeches and slugs.
Suppose we place an animal or a plant cell in a solution of sugar or salt in water.
- If the medium is hypotonic — a dilute solution, with a higher water concentration than the cell — the cell will gain water through osmosis.
- If the medium is isotonic — a solution with exactly the same water concentration as the cell — there will be no net movement of water across the cell membrane.
- If the medium is hypertonic — a concentrated solution, with a lower water concentration than the cell — the cell will lose water by osmosis.
Chemical gardens demonstrate the effect of osmosis in inorganic chemistry.
# Osmotic pressure
As mentioned before, osmosis may be opposed by increasing the pressure in the region of high solute concentration with respect to that in the low solute concentration region. The force per unit area, or pressure, required to prevent the passage of water through a selectively-permeable membrane and into a solution of greater concentration is equivalent to the osmotic pressure of the solution, or turgor. Osmotic pressure is a colligative property, meaning that the property depends on the concentration of the solute but not on its identity.
Increasing the pressure increases the chemical potential of the system in proportion to the molar volume (\delta\mu = \delta PV). Therefore, osmosis stops when the increase in potential due to pressure equals the potential decrease from Equation 1, i.e.:
\delta PV = -RT \ln(1-x_2)\qquad (2)
Where \delta P is the osmotic pressure and V is the molar volume of the solvent.
\delta P = RTx_2/V \qquad (3)
# Reverse osmosis
# Forward osmosis
Osmosis may be used directly to achieve separation of water from a "feed" solution containing unwanted solutes. A "draw" solution of higher osmotic pressure than the feed solution is used to induce a net flow of water through a semi-permeable membrane, such that the feed solution becomes concentrated as the draw solution becomes dilute. The diluted draw solution may then be used directly (as with an ingestible solute like glucose), or sent to a secondary separation process for the removal of the draw solute. This secondary separation can be more efficient than a reverse osmosis process would be alone, depending on the draw solute used and the feedwater treated. Forward osmosis is an area of ongoing research, focusing on applications in desalination, water purification, water treatment, food processing, etc. | Osmosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Osmosis is the spontaneous net movement of water across a semipermeable membrane from a region of low solute concentration to a solution with a high solute concentration, down a solute concentration gradient. It is a physical process in which a solvent moves, without input of energy, across a semi permeable membrane (permeable to the solvent, but not the solute) separating two solutions of different concentrations.[1] Osmosis releases energy, and can be made to do work, as when a growing tree-root splits a stone.
Net movement of solvent is from the less-concentrated (hypotonic) to the more-concentrated (hypertonic) solution, which tends to reduce the difference in concentrations. This effect can be countered by increasing the pressure of the hypertonic solution, with respect to the hypotonic. The osmotic pressure is defined to be the pressure required to maintain an equilibrium, with no net movement of solvent. Osmotic pressure is a colligative property, meaning that the property depends on the molar concentration of the solute but not on its identity. Osmosis is the result of diffusion across a semi-permeable membrane.
Osmosis is important in biological systems as many biological membranes are semipermeable. In general, these membranes are impermeable to organic solutes with large molecules, such as polysaccharides, while permeable to water and small, uncharged solutes. Permeability may depend on solubility properties, charge, or chemistry as well as solute size. Water molecules travel through the plasma cell membrane, tonoplast (vacuole) or protoplast in two ways. Either by diffusing across the phospholipid bilayer directly, or via aquaporins (small transmembrane proteins similar to those in facilitated diffusion and in creating ion channels). Osmosis provides the primary means by which water is transported into and out of cells. The turgor pressure of a cell is largely maintained by osmosis, across the cell membrane, between the cell interior and its relatively hypotonic environment.
# Basic explanation
Consider a permeable membrane, such as visking tubing, with apertures big enough to allow water (solvent) molecules, but not larger solute molecules, to pass through. When this membrane is immersed in liquid it is constantly hit by molecules of the liquid, in motion due to their thermal kinetic energy. In this respect solute and solvent molecules are indistinguishable. At a molecular scale, every time a molecule hits the membrane it has a defined likelihood of passing through. Here, there is a difference: for water molecules this probability is non-zero; for solute molecules it is zero.
Suppose the membrane is in a volume of pure water. In this case, since the circumstances on both sides of the membrane are equivalent, water molecules pass in each direction at the same rate; there is no net flow of water through the membrane.
If there is a solution on one side, and pure water on the other, the membrane is still hit by molecules from both sides at the same rate. However, some of the molecules hitting the membrane from the solution side will be solute molecules, and these will not pass through the membrane. So water molecules pass through the membrane from this side at a slower rate. This will result in a net flow of water to the side with the solution. Assuming the membrane does not break, this net flow will slow and finally stop as the pressure on the solution side becomes such that the movement in each direction is equal: dynamic equilibrium. This could either be due to the water potential on both sides of the membrane being the same, or due to osmosis being inhibited by factors such as pressure potential or Osmotic pressure.
Osmosis can also be explained via the notion of entropy, from statistical mechanics. As above, suppose a permeable membrane separates equal amounts of pure solvent and a solution. Since a solution possesses more entropy than pure solvent, the second law of thermodynamics states that solvent molecules will flow into the solution until the entropy of the combined system is maximized. Notice that, as this happens, the solvent loses entropy while the solution gains entropy. Equilibrium, hence maximum entropy, is achieved when the entropy gradient becomes zero.
# Examples of osmosis
Osmotic pressure is the main cause of support in many plants. The osmotic entry of water raises the turgor pressure exerted against the cell wall, until it equals the osmotic pressure, creating a steady state.
When a plant cell is placed in a hypertonic solution, the water in the cells moves to an area higher in solute concentration, and the cell shrinks and so becomes flaccid. (This means the cell has become plasmolysed - the cell membrane has completely left the cell wall due to lack of water pressure on it; the opposite of turgid.)
Also, osmosis is responsible for the ability of plant roots to suck up water from the soil. Since there are many fine roots, they have a large surface area, water enters the roots by osmosis.
Osmosis can also be seen very effectively when potato slices are added to a high concentration of salt solution. The water from inside the potato moves to the salt solution, causing the potato to shrink and to lose its 'turgor pressure'. The more concentrated the salt solution, the bigger the difference in size and weight of the potato slice.
In unusual environments, osmosis can be very harmful to organisms. For example, freshwater and saltwater aquarium fish placed in water of a different salinity than that they are adapted to will die quickly, and in the case of saltwater fish, rather dramatically. Another example of a harmful osmotic effect is the use of table salt to kill leeches and slugs.
Suppose we place an animal or a plant cell in a solution of sugar or salt in water.
- If the medium is hypotonic — a dilute solution, with a higher water concentration than the cell — the cell will gain water through osmosis.
- If the medium is isotonic — a solution with exactly the same water concentration as the cell — there will be no net movement of water across the cell membrane.
- If the medium is hypertonic — a concentrated solution, with a lower water concentration than the cell — the cell will lose water by osmosis.[2]
Chemical gardens demonstrate the effect of osmosis in inorganic chemistry.
# Osmotic pressure
As mentioned before, osmosis may be opposed by increasing the pressure in the region of high solute concentration with respect to that in the low solute concentration region. The force per unit area, or pressure, required to prevent the passage of water through a selectively-permeable membrane and into a solution of greater concentration is equivalent to the osmotic pressure of the solution, or turgor. Osmotic pressure is a colligative property, meaning that the property depends on the concentration of the solute but not on its identity.
Increasing the pressure increases the chemical potential of the system in proportion to the molar volume (<math>\delta\mu = \delta PV</math>). Therefore, osmosis stops when the increase in potential due to pressure equals the potential decrease from Equation 1, i.e.:
<math>\delta PV = -RT \ln(1-x_2)\qquad (2)</math>
Where <math>\delta P</math> is the osmotic pressure and <math>V</math> is the molar volume of the solvent.
<math>\delta P = RTx_2/V \qquad (3)</math>
# Reverse osmosis
# Forward osmosis
Osmosis may be used directly to achieve separation of water from a "feed" solution containing unwanted solutes. A "draw" solution of higher osmotic pressure than the feed solution is used to induce a net flow of water through a semi-permeable membrane, such that the feed solution becomes concentrated as the draw solution becomes dilute. The diluted draw solution may then be used directly (as with an ingestible solute like glucose), or sent to a secondary separation process for the removal of the draw solute. This secondary separation can be more efficient than a reverse osmosis process would be alone, depending on the draw solute used and the feedwater treated. Forward osmosis is an area of ongoing research, focusing on applications in desalination, water purification, water treatment, food processing, etc. | https://www.wikidoc.org/index.php/Osmosis | |
d0b2e0115a302efc373f04b143fb44618692c89f | wikidoc | Otolith | Otolith
An otolith, (oto-, ear + lithos, a stone), also called statoconium or otoconium is a structure in the saccule or utricle of the inner ear, specifically in the vestibular labyrinth. The saccule and utricle, in turn, together make the otolith organs. They are sensitive to gravity and linear acceleration. Because of their orientation in the head, the utricle is sensitive to a change in horizontal movement, and the saccule gives information about vertical acceleration (such as when in an elevator).
# Mechanism
Otoliths are small particles, composed of a combination of a gelatinous matrix and calcium carbonate in the viscous fluid of the saccule and utricle. The inertia of these small particles causes them to stimulate hair cells when the head moves. The hair cells send signals down sensory nerve fibres, which are interpreted by the brain as motion.
When the head is in a normal upright position, the otolith presses on the sensory hair cell receptors. This pushes the hair cell processes down and prevents them from moving side to side. However, when the head is tilted, the pull of gravity on statoconia shift the hair cell processes to the side, distorting them and sending a message to the central nervous system that the head is no longer level but now tilted.
In 1991, Martin Lenhardt of the University of Virginia discovered that people can hear ultrasonic speech, perhaps using the saccule as a hearing organ.
# Significance in Ichthyology
Finfish (class Osteichthyes) have three pairs of otoliths - the sagittae (singular sagitta), lapilli (singular lapillus), and asterisci (singular asteriscus). The sagittae are largest, found just behind the eyes and approximately level with them vertically. The lapilli and asterisci (smallest of the three) are located within the semicircular canals.
The shapes and proportional sizes of the otoliths vary with fish species. In general, fish from highly structured habitats such as reefs or rocky bottoms (e.g. snappers, groupers, many drums and croakers) will have larger otoliths than fish that spend most of their time swimming at high speed in straight lines in the open ocean (e.g. tuna, mackerel, dolphinfish). Flying fish have unusually large otoliths, possibly due to their need for balance when launching themselves out of the water to "fly" in the air. Often, the fish species can be identified from distinct morphological characteristics of an isolated otolith.
Fish otoliths accrete layers of calcium carbonate and gelatinous matrix throughout their lives. The accretion rate varies with growth of the fish - often less growth in winter and more in summer - which results in the appearance of rings that resemble tree rings. By counting the rings, it is possible to determine the age of the fish in years. Typically the sagitta is used, as it is largest, but sometimes lapilli are used if they have a more convenient shape. The asteriscus, which is smallest of the three, is rarely used in age and growth studies.
In addition, in most species the accretion of calcium carbonate and gelatinous matrix alternates on a daily cycle. It is therefore also possible to determine fish age in days. This latter information is often obtained under a microscope, and provides significant data to early life history studies.
By measuring the thickness of individual rings, it is possible (at least in some species) to estimate fish growth because fish growth is directly proportional to otolith growth. Otoliths, unlike scales, do not reabsorb during times of decreased energy making it even more useful tool to age a fish. Fish never stop growing entirely, though growth rate in mature fish is much reduced. Rings corresponding to later parts of the life cycle tend to be closer together as a result.
Age and growth studies of fish are important for understanding such things as timing and magnitude of spawning, recruitment and habitat use, larval and juvenile duration, and population age structure. Such knowledge is in turn important for designing appropriate fisheries management policies.
The composition of fish otoliths are proving useful to fisheries scientists. The calcium carbonate that composes the otolith is primarily derived from the water. As the otolith grows, new calcium carbonate, mainly aragonite, crystals form. As with any crystal structure, lattice vacancies will exist during crystal formation allowing trace elements from the water to bind with the otolith. Studying the trace elemental composition or isotopic signatures of trace elements within a fish otolith gives insight to the water bodies fish have previously occupied. The most studied trace and isotopic signatures are strontium due to the same charge and similar ionic radius to calcium; however, scientists can study multiple trace elements within an otolith to discriminate more specific signatures. A common tool used to measure trace elements in an otolith is a laser ablation inductively coupled plasma mass spectrometer. This tool can measure a variety of trace elements simultaneously. A secondary ion mass spectrometer can also be used. This instrument can allow for greater chemical resolution but can only measure one trace element at a time. Dr. Steven Campana is one of the leading researchers in the study of otolith trace elemental and isotopic composition. The hope of this research is to provide scientists with valuable information on where fish have traveled. Combined with otolith annuli, scientists can add how old fish were when they traveled through different water bodies. All this information can be used to determine fish life cycles so that fisheries scientists can make informed decisions about fish stocks.
# Significance in Paleontology
After the death and decomposition of a fish, otoliths are dispersed, buried and eventually fossilized. They are one of the many microfossils which can be found though a micropalaeontological analysis of a fine sediment. Their stratigraphic significance is minimal, but can still be used to characterize a level or interval.
The composition of fossilized otoliths can also yield information about the ancient environment. Most notably, stable oxygen isotopes can be used to calculate the water temperature. There are even efforts to study stable oxygen isotopes in modern fish to infer El Nino and La Nina effects. | Otolith
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
An otolith, (oto-, ear + lithos, a stone), also called statoconium[1] or otoconium is a structure in the saccule or utricle of the inner ear, specifically in the vestibular labyrinth. The saccule and utricle, in turn, together make the otolith organs. They are sensitive to gravity and linear acceleration. Because of their orientation in the head, the utricle is sensitive to a change in horizontal movement, and the saccule gives information about vertical acceleration (such as when in an elevator).
# Mechanism
Otoliths are small particles, composed of a combination of a gelatinous matrix and calcium carbonate in the viscous fluid of the saccule and utricle. The inertia of these small particles causes them to stimulate hair cells when the head moves. The hair cells send signals down sensory nerve fibres, which are interpreted by the brain as motion.
When the head is in a normal upright position, the otolith presses on the sensory hair cell receptors. This pushes the hair cell processes down and prevents them from moving side to side. However, when the head is tilted, the pull of gravity on statoconia shift the hair cell processes to the side, distorting them and sending a message to the central nervous system that the head is no longer level but now tilted.
In 1991, Martin Lenhardt of the University of Virginia discovered that people can hear ultrasonic speech, perhaps using the saccule as a hearing organ.[2]
# Significance in Ichthyology
Finfish (class Osteichthyes) have three pairs of otoliths - the sagittae (singular sagitta), lapilli (singular lapillus), and asterisci (singular asteriscus). The sagittae are largest, found just behind the eyes and approximately level with them vertically. The lapilli and asterisci (smallest of the three) are located within the semicircular canals.
The shapes and proportional sizes of the otoliths vary with fish species. In general, fish from highly structured habitats such as reefs or rocky bottoms (e.g. snappers, groupers, many drums and croakers) will have larger otoliths than fish that spend most of their time swimming at high speed in straight lines in the open ocean (e.g. tuna, mackerel, dolphinfish). Flying fish have unusually large otoliths, possibly due to their need for balance when launching themselves out of the water to "fly" in the air. Often, the fish species can be identified from distinct morphological characteristics of an isolated otolith.
Fish otoliths accrete layers of calcium carbonate and gelatinous matrix throughout their lives. The accretion rate varies with growth of the fish - often less growth in winter and more in summer - which results in the appearance of rings that resemble tree rings. By counting the rings, it is possible to determine the age of the fish in years.[3] Typically the sagitta is used, as it is largest,[4] but sometimes lapilli are used if they have a more convenient shape. The asteriscus, which is smallest of the three, is rarely used in age and growth studies.
In addition, in most species the accretion of calcium carbonate and gelatinous matrix alternates on a daily cycle. It is therefore also possible to determine fish age in days. This latter information is often obtained under a microscope, and provides significant data to early life history studies.
By measuring the thickness of individual rings, it is possible (at least in some species) to estimate fish growth because fish growth is directly proportional to otolith growth. Otoliths, unlike scales, do not reabsorb during times of decreased energy making it even more useful tool to age a fish. Fish never stop growing entirely, though growth rate in mature fish is much reduced. Rings corresponding to later parts of the life cycle tend to be closer together as a result.
Age and growth studies of fish are important for understanding such things as timing and magnitude of spawning, recruitment and habitat use, larval and juvenile duration, and population age structure. Such knowledge is in turn important for designing appropriate fisheries management policies.
The composition of fish otoliths are proving useful to fisheries scientists. The calcium carbonate that composes the otolith is primarily derived from the water. As the otolith grows, new calcium carbonate, mainly aragonite, crystals form. As with any crystal structure, lattice vacancies will exist during crystal formation allowing trace elements from the water to bind with the otolith. Studying the trace elemental composition or isotopic signatures of trace elements within a fish otolith gives insight to the water bodies fish have previously occupied. The most studied trace and isotopic signatures are strontium due to the same charge and similar ionic radius to calcium; however, scientists can study multiple trace elements within an otolith to discriminate more specific signatures. A common tool used to measure trace elements in an otolith is a laser ablation inductively coupled plasma mass spectrometer. This tool can measure a variety of trace elements simultaneously. A secondary ion mass spectrometer can also be used. This instrument can allow for greater chemical resolution but can only measure one trace element at a time. Dr. Steven Campana is one of the leading researchers in the study of otolith trace elemental and isotopic composition. The hope of this research is to provide scientists with valuable information on where fish have traveled. Combined with otolith annuli, scientists can add how old fish were when they traveled through different water bodies. All this information can be used to determine fish life cycles so that fisheries scientists can make informed decisions about fish stocks.
# Significance in Paleontology
After the death and decomposition of a fish, otoliths are dispersed, buried and eventually fossilized. They are one of the many microfossils which can be found though a micropalaeontological analysis of a fine sediment. Their stratigraphic significance is minimal, but can still be used to characterize a level or interval.
The composition of fossilized otoliths can also yield information about the ancient environment. Most notably, stable oxygen isotopes can be used to calculate the water temperature. There are even efforts to study stable oxygen isotopes in modern fish to infer El Nino and La Nina effects. | https://www.wikidoc.org/index.php/Otoconia | |
c4e9ab95a2c31fc0825e3eb7aa9871766b86cbbb | wikidoc | Outlier | Outlier
# Overview
In statistics such as stratified samples, an outlier is an observation that is numerically distant from the rest of the data. Statistics derived from data sets that include outliers will often be misleading. For example, if one is calculating the average temperature of 10 objects in a room, and most are between 20-25° Celsius, but an oven is at 350° C, the median of the data may be 23 but the mean temperature will be 55. In this case, the median better reflects the temperature of a randomly sampled object than the mean. Outliers may be indicative of data points that belong to a different population than the rest of the sample set.
In most samplings of data, some data points will be further away from their expected values than what is deemed reasonable. This can be due to systematic error, faults in the theory that generated the expected values, or it can simply be the case that some observations happen to be a long way from the center of the data. Outlier points can therefore indicate faulty data, erroneous procedures, or areas where a certain theory might not be valid. However, a small number of outliers is expected in normal distributions.
Estimators not sensitive to outliers are said to be robust.
Deletion of outlier data is a controversial practice frowned on by many scientists and science instructors; while mathematical criteria provides an objective and quantitiative method for data rejection, it does not make the practice more scientifically or methodologically sound, especially in small sets or where a normal distribution cannot be assumed. Rejection of outliers is more acceptable in areas of practice where the underlying model of the process being measured and the usual distribution of measurement error are confidently known. When practiced, rejection of outliers usually is based on some rule such as the quartile rules given below, Chauvenet's Criterion, or Grubbs Test.
# Mathematical definitions
## Mild outliers
Defining Q_1 and Q_3 to be first and third quartiles, and IQR to be the interquartile range (Q_3-Q_1), one possible definition of being "far away" in this context is:
-r
Q_1 and Q_3 define the so-called inner fences, beyond which an observation would be labeled a mild outlier.
## Extreme outliers
Extreme outliers are observations that are beyond the outer fences:
-r
## Occurrence and causes
In the case of normally distributed data, using the above definitions, only about 1 in 150 observations will be a mild outlier, and only about 1 in 425,000 an extreme outlier. Because of this, outliers usually demand special attention, since they may indicate problems in sampling or data collection or transcription.
Alternatively, an outlier could be the result of a flaw in the assumed theory, calling for further investigation by the researcher.
## Non-normal distributions
Even when a normal distribution model is appropriate to the data being analyzed, outliers are expected for large sample sizes and should not automatically be discarded if that is the case. Also, the possibility should be considered that the underlying distribution of the data is not approximately normal, having "fat tails". For instance, when sampling from a Cauchy distribution, the sample variance increases with the sample size, the sample mean fails to converge as the sample size increases, and outliers are expected at far larger rates than for a normal distribution. Outliers play an important role in statistics. | Outlier
# Overview
In statistics such as stratified samples, an outlier is an observation that is numerically distant from the rest of the data. Statistics derived from data sets that include outliers will often be misleading. For example, if one is calculating the average temperature of 10 objects in a room, and most are between 20-25° Celsius, but an oven is at 350° C, the median of the data may be 23 but the mean temperature will be 55. In this case, the median better reflects the temperature of a randomly sampled object than the mean. Outliers may be indicative of data points that belong to a different population than the rest of the sample set.
In most samplings of data, some data points will be further away from their expected values than what is deemed reasonable. This can be due to systematic error, faults in the theory that generated the expected values, or it can simply be the case that some observations happen to be a long way from the center of the data. Outlier points can therefore indicate faulty data, erroneous procedures, or areas where a certain theory might not be valid. However, a small number of outliers is expected in normal distributions.
Estimators not sensitive to outliers are said to be robust.
Deletion of outlier data is a controversial practice frowned on by many scientists and science instructors; while mathematical criteria provides an objective and quantitiative method for data rejection, it does not make the practice more scientifically or methodologically sound, especially in small sets or where a normal distribution cannot be assumed. Rejection of outliers is more acceptable in areas of practice where the underlying model of the process being measured and the usual distribution of measurement error are confidently known. When practiced, rejection of outliers usually is based on some rule such as the quartile rules given below, Chauvenet's Criterion, or Grubbs Test.
# Mathematical definitions
## Mild outliers
Defining <math>Q_1</math> and <math>Q_3</math> to be first and third quartiles, and <math>IQR</math> to be the interquartile range (<math>Q_3-Q_1</math>), one possible definition of being "far away" in this context is:
or
<math>Q_1</math> and <math>Q_3</math> define the so-called inner fences, beyond which an observation would be labeled a mild outlier.
## Extreme outliers
Extreme outliers are observations that are beyond the outer fences:
or
## Occurrence and causes
In the case of normally distributed data, using the above definitions, only about 1 in 150 observations will be a mild outlier, and only about 1 in 425,000 an extreme outlier. Because of this, outliers usually demand special attention, since they may indicate problems in sampling or data collection or transcription.
Alternatively, an outlier could be the result of a flaw in the assumed theory, calling for further investigation by the researcher.
## Non-normal distributions
Even when a normal distribution model is appropriate to the data being analyzed, outliers are expected for large sample sizes and should not automatically be discarded if that is the case. Also, the possibility should be considered that the underlying distribution of the data is not approximately normal, having "fat tails". For instance, when sampling from a Cauchy distribution, the sample variance increases with the sample size, the sample mean fails to converge as the sample size increases, and outliers are expected at far larger rates than for a normal distribution. Outliers play an important role in statistics. | https://www.wikidoc.org/index.php/Outlier | |
81f015f4dfaa8cac4ed3808975c899778f46a88c | wikidoc | Oxalate | Oxalate
# Overview
An oxalate (also ethanedioate) is a salt or ester of oxalic acid. As a salt, the oxalate anion has the chemical formula C2O42− or (COO)22−.
Consumption of oxalates (for example, the grazing of animals on oxalate-containing plants such as greasewood), or human consumption of Sorrel may result in kidney disease or even death due to oxalate poisoning.
The charge on oxalate allows it to act as a chelator of various positively charged metal ions.
Much of its other properties resemble oxalic acid.
# Examples
- sodium oxalate - Na2C2O4
- calcium oxalate - CaC2O4, a major component of kidney stones
- dimethyl oxalate - (CH3)2C2O4
- phenyl oxalate ester - (C6H5)2C2O4
- potassium ferrioxalate - , an iron complex with oxalate ligands
- ammonium oxalate - (NH4)2C2O4 | Oxalate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An oxalate (also ethanedioate) is a salt or ester of oxalic acid. As a salt, the oxalate anion has the chemical formula C2O42− or (COO)22−.
Consumption of oxalates (for example, the grazing of animals on oxalate-containing plants such as greasewood), or human consumption of Sorrel may result in kidney disease or even death due to oxalate poisoning.
The charge on oxalate allows it to act as a chelator of various positively charged metal ions.
Much of its other properties resemble oxalic acid.
# Examples
- sodium oxalate - Na2C2O4
- calcium oxalate - CaC2O4, a major component of kidney stones
- dimethyl oxalate - (CH3)2C2O4
- phenyl oxalate ester - (C6H5)2C2O4
- potassium ferrioxalate - [K3[Fe(C2O4)3], an iron complex with oxalate ligands
- ammonium oxalate - (NH4)2C2O4 | https://www.wikidoc.org/index.php/Oxalate | |
f4f2e6ea484f8daf54acf746a56e790991d3bec4 | wikidoc | Oxoacid | Oxoacid
# Overview
An oxoacid is an acid which contains oxygen. More specifically, it is an acid which:
- contains oxygen;
- contains at least one other element;
- has at least one hydrogen atom bound to oxygen; and
- forms an ion by the loss of one or more protons.
The name oxyacid is sometimes used, although this is not recommended.
Generally, oxoacids are simply polyatomic ions with a hydrogen cation.
Under Lavoisier's original theory, all acids contained oxygen, which was named from the Greek οξυς (oxys) (acid, sharp) and γεινομαι (geinomai) (engender). It was later discovered that some acids, notably hydrochloric acid, did not contain oxygen and so a distinction was made for those that did.
Common oxoacids include:
- Halogen oxoacids: Hypochlorous acid; Chlorous acid; Chloric acid; Perchloric acid; Perbromic acid; Metaperiodic acid
- Sulfuric acid
- Nitric acid
- Phosphoric acid
Common acids which are not oxoacids include:
- Hydrochloric acid
- Hydrofluoric acid
- Hydrobromic acid
- Hydroiodic acid
Although carboxylic acids fulfill the criteria above, they are not generally considered as oxoacids.
All oxoacids have the acidic hydrogen bound to an oxygen atom, so bond strength (length) is not a factor as it is with binary nonmetal hydrides. Rather, the electronegativity of the central atom (E) and the number of O atoms determine oxoacid acidity. With the same number of oxygens around E, acid strength increases with the electronegativity of E.
# Note
- ^ This final criterion has the effect of excluding boric acid from the strict definition, as it forms its anion by addition of hydroxide rather than loss of a proton: B(OH)3 + H2O − + H+. However, boric acid is usually considered to be an oxoacid nonetheless. | Oxoacid
# Overview
An oxoacid is an acid which contains oxygen. More specifically, it is an acid which:
- contains oxygen;
- contains at least one other element;
- has at least one hydrogen atom bound to oxygen; and
- forms an ion by the loss of one or more protons.[1]
The name oxyacid is sometimes used, although this is not recommended.
Generally, oxoacids are simply polyatomic ions with a hydrogen cation.
Under Lavoisier's original theory, all acids contained oxygen, which was named from the Greek οξυς (oxys) (acid, sharp) and γεινομαι (geinomai) (engender). It was later discovered that some acids, notably hydrochloric acid, did not contain oxygen and so a distinction was made for those that did.
Common oxoacids include:
- Halogen oxoacids: Hypochlorous acid; Chlorous acid; Chloric acid; Perchloric acid; Perbromic acid; Metaperiodic acid
- Sulfuric acid
- Nitric acid
- Phosphoric acid
Common acids which are not oxoacids include:
- Hydrochloric acid
- Hydrofluoric acid
- Hydrobromic acid
- Hydroiodic acid
Although carboxylic acids fulfill the criteria above, they are not generally considered as oxoacids.
All oxoacids have the acidic hydrogen bound to an oxygen atom, so bond strength (length) is not a factor as it is with binary nonmetal hydrides. Rather, the electronegativity of the central atom (E) and the number of O atoms determine oxoacid acidity. With the same number of oxygens around E, acid strength increases with the electronegativity of E.
# Note
- ^ This final criterion has the effect of excluding boric acid from the strict definition, as it forms its anion by addition of hydroxide rather than loss of a proton: B(OH)3 + H2O [B(OH)4]− + H+. However, boric acid is usually considered to be an oxoacid nonetheless. | https://www.wikidoc.org/index.php/Oxoacid | |
aff4deefb3a29d9662cd51814f2f3fc698d85e55 | wikidoc | Oxydose | Oxydose
Oxydose®
ÃHX'-ē-dōsè (proper noun)
1. Oxydose® is a liquid opioid narcotic elixir. Its active ingredient is oxycodone hydrochloride U.S.P., a U.S. Schedule II opioid. It is prescribed for severe pain, where immediate pain relief is required, sometimes relieving intractable pain in up to five minutes when used sublingually. Oxycodone Hydrochloride is also used in other preparations such as Percocet Roxicodone and other prescription pain killers. Oxydose® is highly concentrated in a vanilla & grape flavored liquid vehicle containing 20mg/ml. Oxydose is currently manufactured by Ethex Pharmaceuticals.
Oxycodone, like most opioids has a potential for abuse and dependence and therefore may be habit-forming.
see also, OxyFast® C-II (oxycodone HCl immediate-release) Oral Concentrate Solution (the Brand name equivalent for Oxydose, a registered trademark of Purdue Pharma) | Oxydose
Oxydose®
ÃHX'-ē-dōsè (proper noun)
1. Oxydose® is a liquid opioid narcotic elixir. Its active ingredient is oxycodone hydrochloride U.S.P., a U.S. Schedule II opioid. It is prescribed for severe pain, where immediate pain relief is required, sometimes relieving intractable pain in up to five minutes when used sublingually. Oxycodone Hydrochloride is also used in other preparations such as Percocet Roxicodone and other prescription pain killers. Oxydose® is highly concentrated in a vanilla & grape flavored liquid vehicle containing 20mg/ml. Oxydose is currently manufactured by Ethex Pharmaceuticals.
Oxycodone, like most opioids has a potential for abuse and dependence and therefore may be habit-forming.
see also, OxyFast® C-II (oxycodone HCl immediate-release) Oral Concentrate Solution (the Brand name equivalent for Oxydose, a registered trademark of Purdue Pharma)
# External links
- Ethex Pharmaceuticals - Oxydose
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Oxydose | |
e6e207d1061f0a1f3fa6eca4e31e8df177bd7861 | wikidoc | Ozonide | Ozonide
Ozonide is an unstable, reactive polyatomic anion O3−, derived from ozone, or an organic compound similar to organic peroxide formed by a reaction of ozone with an unsaturated compound.
# Inorganic ozonides
Inorganic ozonides are dark red ionic compounds containing the reactive O3− anion. The anion has the V shape of the ozone molecule.
Inorganic ozonides are formed by burning potassium or heavier alkali metals in ozone, or by treating the alkali metal hydroxide with ozone; if potassium is left undisturbed in air for years it accumulates a covering of superoxide and ozonide. They are very sensitive explosives that have to be handled at low temperatures in an atmosphere comprised of an inert gas. Lithium and sodium ozonide are extremely unstable and must be prepared by low-temperature ion exchange starting from CsO3, and the pure solids cannot be isolated.
Inorganic ozonides are being investigated as promising sources of oxygen in chemical oxygen generators.
# Organic ozonides
Organic ozonides are more explosive cousins of the organic peroxides and contain a covalently bonded ozonide group, -O-O-O-. They usually appear in the form of foul-smelling oily liquids. Their main use is in determining the structure of chemical compounds. As intermediates of ozonolysis, they are formed by an addition reaction of ozone and unsaturated compounds, and rapidly decompose to carbonyl compounds - aldehydes, ketones, peroxides. | Ozonide
Ozonide is an unstable, reactive polyatomic anion O3−, derived from ozone, or an organic compound similar to organic peroxide formed by a reaction of ozone with an unsaturated compound.
# Inorganic ozonides
Inorganic ozonides are dark red ionic compounds containing the reactive O3− anion. The anion has the V shape of the ozone molecule.
Inorganic ozonides are formed by burning potassium or heavier alkali metals in ozone, or by treating the alkali metal hydroxide with ozone; if potassium is left undisturbed in air for years it accumulates a covering of superoxide and ozonide. They are very sensitive explosives that have to be handled at low temperatures in an atmosphere comprised of an inert gas. Lithium and sodium ozonide are extremely unstable and must be prepared by low-temperature ion exchange starting from CsO3, and the pure solids cannot be isolated.
Inorganic ozonides are being investigated as promising sources of oxygen in chemical oxygen generators.
# Organic ozonides
Organic ozonides are more explosive cousins of the organic peroxides and contain a covalently bonded ozonide group, -O-O-O-. They usually appear in the form of foul-smelling oily liquids. Their main use is in determining the structure of chemical compounds. As intermediates of ozonolysis, they are formed by an addition reaction of ozone and unsaturated compounds, and rapidly decompose to carbonyl compounds - aldehydes, ketones, peroxides. | https://www.wikidoc.org/index.php/Ozonide | |
9381978421d701e47e2661ef158fddfad9ac0978 | wikidoc | P-value | P-value
# Overview
In statistical hypothesis testing, the p-value is the probability of obtaining a result at least as extreme as a given data point, assuming the data point was the result of chance alone. The fact that p-values are based on this assumption is crucial to their correct interpretation. The p-value may be noted as a decimal: p-value < 0.05 means that the likelihood that the event occurred by chance alone is less than 5%. The lower the p-value, the less likely the event would occur by chance alone.
# Coin flipping example
For example, say an experiment is performed to determine if a coin flip is fair (50% chance of landing heads or tails), or unfairly biased, either toward heads (> 50% chance of landing heads) or toward tails (< 50% chance of landing heads). Since we consider both biased alternatives, a two-tailed test is performed. The null hypothesis is that the coin is fair, and that any deviations from the 50% rate can be ascribed to chance alone. Suppose that the experimental results show the coin turning up heads 14 times out of 20 total flips. The p-value of this result would be the chance of a fair coin landing on heads at least 14 times out of 20 flips (as larger values in this case are also less favorable to the null hypothesis of a fair coin) or landing on tails at most 6 times out of 20 flips. In this case the random variable T has a binomial distribution. The probability that 20 flips of a fair coin would result in 14 or more heads is 0.0577. Since this is a two-tailed test, the probability that 20 flips of the coin would result in 14 or more heads or 6 or less heads is 0.0577 x 2 = 0.115.
Generally, the smaller the p-value, the more people there are who would be willing to say that the results came from a biased coin.
# Interpretation
Generally, one rejects the null hypothesis if the p-value is smaller than or equal to the significance level, often represented by the Greek letter α (alpha). If the level is 0.05, then the results are only 5% likely to be as extraordinary as just seen, given that the null hypothesis is true.
In the above example, the calculated p-value exceeds 0.05, and thus the null hypothesis - that the observed result of 14 heads out of 20 flips can be ascribed to chance alone - is not rejected. Such a finding is often stated as being "not statistically significant at the 5% level".
However, had a single extra head been obtained, the resulting p-value would be 0.02. This time the null hypothesis - that the observed result of 15 heads out of 20 flips can be ascribed to chance alone - is rejected. Such a finding would be described as being "statistically significant at the 5% level".
Critics of p-values point out that the criterion used to decide "statistical significance" is based on the somewhat arbitrary choice of level (often set at 0.05). A proposed replacement for the p-value is p-rep.
# Frequent misunderstandings
There are several common misunderstandings about p-values.
- The p-value is not the probability that the null hypothesis is true (claimed to justify the "rule" of considering as significant p-values closer to 0 (zero)).
In fact, frequentist statistics does not, and cannot, attach probabilities to hypotheses. Comparison of Bayesian and classical approaches shows that a p-value can be very close to zero while the posterior probability of the null is very close to unity. This is the Jeffreys-Lindley paradox.
- The p-value is not the probability that a finding is "merely a fluke" (again, justifying the "rule" of considering small p-values as "significant").
As the calculation of a p-value is based on the assumption that a finding is the product of chance alone, it patently cannot simultaneously be used to gauge the probability of that assumption being true.
- The p-value is not the probability of falsely rejecting the null hypothesis. This error is a version of the so-called prosecutor's fallacy.
- The p-value is not the probability that a replicating experiment would not yield the same conclusion.
- 1 − (p-value) is not the probability of the alternative hypothesis being true (see (1)).
- The significance level of the test is not determined by the p-value.
The significance level of a test is a value that should be decided upon by the agent interpreting the data before the data are viewed, and is compared against the p-value or any other statistic calculated after the test has been performed.
- The p-value does not indicate the size or importance of the observed effect (compare with effect size). | P-value
# Overview
In statistical hypothesis testing, the p-value is the probability of obtaining a result at least as extreme as a given data point, assuming the data point was the result of chance alone. The fact that p-values are based on this assumption is crucial to their correct interpretation. The p-value may be noted as a decimal: p-value < 0.05 means that the likelihood that the event occurred by chance alone is less than 5%. The lower the p-value, the less likely the event would occur by chance alone.[1]
# Coin flipping example
For example, say an experiment is performed to determine if a coin flip is fair (50% chance of landing heads or tails), or unfairly biased, either toward heads (> 50% chance of landing heads) or toward tails (< 50% chance of landing heads). Since we consider both biased alternatives, a two-tailed test is performed. The null hypothesis is that the coin is fair, and that any deviations from the 50% rate can be ascribed to chance alone. Suppose that the experimental results show the coin turning up heads 14 times out of 20 total flips. The p-value of this result would be the chance of a fair coin landing on heads at least 14 times out of 20 flips (as larger values in this case are also less favorable to the null hypothesis of a fair coin) or landing on tails at most 6 times out of 20 flips. In this case the random variable T has a binomial distribution. The probability that 20 flips of a fair coin would result in 14 or more heads is 0.0577. Since this is a two-tailed test, the probability that 20 flips of the coin would result in 14 or more heads or 6 or less heads is 0.0577 x 2 = 0.115.
Generally, the smaller the p-value, the more people there are who would be willing to say that the results came from a biased coin.
# Interpretation
Generally, one rejects the null hypothesis if the p-value is smaller than or equal to the significance level, often represented by the Greek letter α (alpha). If the level is 0.05, then the results are only 5% likely to be as extraordinary as just seen, given that the null hypothesis is true.
In the above example, the calculated p-value exceeds 0.05, and thus the null hypothesis - that the observed result of 14 heads out of 20 flips can be ascribed to chance alone - is not rejected. Such a finding is often stated as being "not statistically significant at the 5% level".
However, had a single extra head been obtained, the resulting p-value would be 0.02. This time the null hypothesis - that the observed result of 15 heads out of 20 flips can be ascribed to chance alone - is rejected. Such a finding would be described as being "statistically significant at the 5% level".
Critics of p-values point out that the criterion used to decide "statistical significance" is based on the somewhat arbitrary choice of level (often set at 0.05). A proposed replacement for the p-value is p-rep.
# Frequent misunderstandings
There are several common misunderstandings about p-values.[2]
- The p-value is not the probability that the null hypothesis is true (claimed to justify the "rule" of considering as significant p-values closer to 0 (zero)).
In fact, frequentist statistics does not, and cannot, attach probabilities to hypotheses. Comparison of Bayesian and classical approaches shows that a p-value can be very close to zero while the posterior probability of the null is very close to unity. This is the Jeffreys-Lindley paradox.
- The p-value is not the probability that a finding is "merely a fluke" (again, justifying the "rule" of considering small p-values as "significant").
As the calculation of a p-value is based on the assumption that a finding is the product of chance alone, it patently cannot simultaneously be used to gauge the probability of that assumption being true.
- The p-value is not the probability of falsely rejecting the null hypothesis. This error is a version of the so-called prosecutor's fallacy.
- The p-value is not the probability that a replicating experiment would not yield the same conclusion.
- 1 − (p-value) is not the probability of the alternative hypothesis being true (see (1)).
- The significance level of the test is not determined by the p-value.
The significance level of a test is a value that should be decided upon by the agent interpreting the data before the data are viewed, and is compared against the p-value or any other statistic calculated after the test has been performed.
- The p-value does not indicate the size or importance of the observed effect (compare with effect size). | https://www.wikidoc.org/index.php/P-value | |
cf28f06b9511f40f5cad54c0eea07b53aebec979 | wikidoc | PCDH11X | PCDH11X
Protocadherin 11 X-linked, also known as PCDH11X, is a protein which in humans is encoded by the PCDH11X gene.
# Function
This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog (PCDHY), despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell–cell recognition essential for the segmental development and function of the central nervous system. Transcripts arising from alternative splicing encode isoforms with variable cytoplasmic domains.
# Clinical significance
In a genome-wide association study, the PCDH11X gene has been linked as a risk factor in late onset Alzheimer's disease, but other studies on different populations could not confirm the initial association. The clinical significance of this gene is unclear, and the gene might play different roles in different population specific contexts. | PCDH11X
Protocadherin 11 X-linked, also known as PCDH11X, is a protein which in humans is encoded by the PCDH11X gene.[1][2]
# Function
This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog (PCDHY), despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell–cell recognition essential for the segmental development and function of the central nervous system. Transcripts arising from alternative splicing encode isoforms with variable cytoplasmic domains.[1]
# Clinical significance
In a genome-wide association study, the PCDH11X gene has been linked as a risk factor in late onset Alzheimer's disease,[3] but other studies on different populations [4][5][6][7] could not confirm the initial association. The clinical significance of this gene is unclear, and the gene might play different roles in different population specific contexts. | https://www.wikidoc.org/index.php/PCDH11X | |
647a0e413a959173d98c5c58f08adab4cfca8e4b | wikidoc | PDBWiki | PDBWiki
PDBWiki is a user contributed database of protein structure annotations, listing all the protein structures currently available in the Protein Data Bank (PDB). The aims of PDBWiki, focusing on user contributed annotation and classification, have been met by the use of the MediaWiki software system, making PDBWiki a 'Wiki-Database'.
# Motivation
The Protein Data Bank (PDB) is the central archive of experimentally solved biomolecular structures. However, the PDB only allows data retrieval and does not provide functionality for collaboration or user feedback. In contrast, PDBWiki is a website for sharing expert knowledge about structures deposited in the PDB. Using the same MediaWiki system underlying Wikipedia] it provides online tools for discussing and annotating proteins in a collaborative way. The goal is to create a central and freely accessible repository of user-contributed information that will be useful for anyone working with PDB structures. As such PDBWiki can be considered a part of a wider effort in community-based biological databases curation.
# Database content
Currently PDBWiki contains details of more than 50,000 protein structures and over 50 'user-contributed' annotations, making it a significant resource for the structural biology community.
# About
PDBWiki was developed as part of the BioWiki initiative, and was entered into the third International Openfree Bioinformation Contents Competition organised by BiO.CC, the top level biological information web site operated by KOBIC. | PDBWiki
PDBWiki is a user contributed database of protein structure annotations, listing all the protein structures currently available in the Protein Data Bank (PDB). The aims of PDBWiki, focusing on user contributed annotation and classification, have been met by the use of the MediaWiki software system, making PDBWiki a 'Wiki-Database'. [1]
# Motivation
The Protein Data Bank (PDB) is the central archive of experimentally solved biomolecular structures. However, the PDB only allows data retrieval and does not provide functionality for collaboration or user feedback. In contrast, PDBWiki is a website for sharing expert knowledge about structures deposited in the PDB. Using the same MediaWiki system underlying Wikipedia] it provides online tools for discussing and annotating proteins in a collaborative way. The goal is to create a central and freely accessible repository of user-contributed information that will be useful for anyone working with PDB structures. As such PDBWiki can be considered a part of a wider effort in community-based biological databases curation. [2]
# Database content
Currently PDBWiki contains details of more than 50,000 protein structures and over 50 'user-contributed' annotations, making it a significant resource for the structural biology community.
# About
PDBWiki was developed as part of the BioWiki initiative, and was entered into the third International Openfree Bioinformation Contents Competition organised by BiO.CC, the top level biological information web site operated by KOBIC. | https://www.wikidoc.org/index.php/PDBWiki | |
21d8a1a8be6875b88e44cf1236724471b6bcf155 | wikidoc | PEG 400 | PEG 400
PEG 400 (Polyethylene Glycol 400) is a low molecular weight grade of Polyethylene glycol. It is a clear, colorless, viscous liqid. Due in part to its low toxicity, PEG 400 is widely used in a variety of pharmaceutical formulations.
# Additional Properties
PEG 400 is strongly hydrophilic. The partition coefficient of polyethylene glycol 414 between hexane and water is 0.000015 (log P = -4.8), indicating that when polyethylene glycol 414 is mixed with water and hexane, there are only 1.5 parts of polyethylene glycol 414 in the hexane layer per 100,000 parts of polyethylene glycol 414 in the water layer.
PEG 400 is soluble in water, acetone, alcohols, benzene, glycerin, glycols, aromatic hydrocarbons and is slightly soluble in aliphatic hydrocarbons. | PEG 400
PEG 400 (Polyethylene Glycol 400) is a low molecular weight grade of Polyethylene glycol. It is a clear, colorless, viscous liqid. Due in part to its low toxicity, PEG 400 is widely used in a variety of pharmaceutical formulations.
# Additional Properties
PEG 400 is strongly hydrophilic. The partition coefficient of polyethylene glycol 414 between hexane and water is 0.000015 (log <math>P = -4.8</math>), indicating that when polyethylene glycol 414 is mixed with water and hexane, there are only 1.5 parts of polyethylene glycol 414 in the hexane layer per 100,000 parts of polyethylene glycol 414 in the water layer.[1]
PEG 400 is soluble in water, acetone, alcohols, benzene, glycerin, glycols, aromatic hydrocarbons and is slightly soluble in aliphatic hydrocarbons. | https://www.wikidoc.org/index.php/PEG_400 | |
325d5908fc05e184cfad131383a9d66950549978 | wikidoc | PHACTR1 | PHACTR1
Phosphatase and actin regulator 1 (PHACTR1) is a protein that in humans is encoded by the PHACTR1 gene on chromosome 6.
It is most significantly expressed in the globus pallidus of the brain. PHACTR1 is an actin and protein phosphatase 1 (PP1) binding protein that binds actin and regulates the reorganization of the actin cytoskeleton. This protein has been associated with coronary artery disease and migraines through genome-wide association studies. The PHACTR1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
# Structure
## Gene
The PHACTR1 gene resides on chromosome 6 at the band 6p24.1 and includes 19 exons. This gene produces 2 isoforms through alternative splicing.
## Protein
PHACTR1 is a member of the phosphatase and actin regulator family and contains 4 RPEL repeats, three of which reside at the C-terminal and bind three actin monomers. PHACTR1 binds actin and PP1 in the region containing these RPEL repeats. As a PHACTR protein, PHACTR1 differs from other PP1-binding proteins in that it is missing the R/K-R/K-hydrophobic-X-F/W consensus sequence, indicating that it binds PP1 at a different site. PHACTR1 is also predicted to contain 8 PKA phosphorylation sites and 7 PKC phosphorylation sites found near the RPEL repeats.
# Function
PHACTR1 is a PP1 binding protein, which is reported to be highly expressed in brain and which controls PP1 activity and F-actin remodeling. PHACTR1 can be induced by NRP and VEGF through NRP-1 and VEGF-R1 receptors to control tubulogenesis, actin polymerization, and lamellipodial dynamics. Through this function, PHACTR1 is suggested to play a role in cell motility and vascular morphogenesis. Meanwhile, suppression of PHACTR1 increases expression of death cell receptors, leading to extrinsic apoptosis.
The PHACTR1 locus is commonly identified in multiple genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, little is known about the function of PHACTR1 in the heart.
# Clinical Significance
Upregulation of PHACTR1 by transforming growth factor (TGF)-β has been described in breast cancer cell lines, potentially pointing to a connection with the TGF-β signaling pathway, which is also implicated in genetic predisposition to migraines and has a key role in Marfan and Loeys-Dietz syndromes, two inherited connective tissue disorders causing aortic dissection.
In humans, genome-wide association studies have linked PHACTR1 to coronary artery disease. Considering that arterial calcification is a well-known risk factor for coronary artery disease and myocardial infarction, one study tested ∼2.5 million SNPs for an association with coronary artery calcification and aortic calcification in 2620 male individuals who were current or former heavy smokers and underwent chest CT scans in the NELSON trial. No SNPs were associated with aortic calcification on a genome-wide scale. The 9p21 locus was significantly associated with coronary artery calcification (rs1537370). Subsequently, two loci at ADAMTS7 (rs3825807) and at PHACTR1 (rs12526453) showed a nominally significant association with coronary artery calcification and an increased degree of arterial calcification.
## Clinical Marker
Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the PHACTR1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).
Another genome-wide association study in 2,326 clinic-based German and Dutch individuals with migraine without aura identified that PHACTR1 (together with ASTN2) as susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. | PHACTR1
Phosphatase and actin regulator 1 (PHACTR1) is a protein that in humans is encoded by the PHACTR1 gene on chromosome 6.
[1] It is most significantly expressed in the globus pallidus of the brain.[2] PHACTR1 is an actin and protein phosphatase 1 (PP1) binding protein that binds actin and regulates the reorganization of the actin cytoskeleton.[3] This protein has been associated with coronary artery disease and migraines through genome-wide association studies.[4][5] The PHACTR1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.[5]
# Structure
## Gene
The PHACTR1 gene resides on chromosome 6 at the band 6p24.1 and includes 19 exons.[1] This gene produces 2 isoforms through alternative splicing.[6]
## Protein
PHACTR1 is a member of the phosphatase and actin regulator family and contains 4 RPEL repeats, three of which reside at the C-terminal and bind three actin monomers.[6] PHACTR1 binds actin and PP1 in the region containing these RPEL repeats. As a PHACTR protein, PHACTR1 differs from other PP1-binding proteins in that it is missing the R/K-R/K-hydrophobic-X-F/W consensus sequence, indicating that it binds PP1 at a different site. PHACTR1 is also predicted to contain 8 PKA phosphorylation sites and 7 PKC phosphorylation sites found near the RPEL repeats.[7]
# Function
PHACTR1 is a PP1 binding protein, which is reported to be highly expressed in brain and which controls PP1 activity and F-actin remodeling.[8] PHACTR1 can be induced by NRP and VEGF through NRP-1 and VEGF-R1 receptors to control tubulogenesis, actin polymerization, and lamellipodial dynamics.[9] Through this function, PHACTR1 is suggested to play a role in cell motility and vascular morphogenesis.[10] Meanwhile, suppression of PHACTR1 increases expression of death cell receptors, leading to extrinsic apoptosis.[8]
The PHACTR1 locus is commonly identified in multiple genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, little is known about the function of PHACTR1 in the heart.[10]
# Clinical Significance
Upregulation of PHACTR1 by transforming growth factor (TGF)-β has been described in breast cancer cell lines, potentially pointing to a connection with the TGF-β signaling pathway, which is also implicated in genetic predisposition to migraines and has a key role in Marfan and Loeys-Dietz syndromes, two inherited connective tissue disorders causing aortic dissection.[11][12]
In humans, genome-wide association studies have linked PHACTR1 to coronary artery disease.[4] Considering that arterial calcification is a well-known risk factor for coronary artery disease and myocardial infarction, one study tested ∼2.5 million SNPs for an association with coronary artery calcification and aortic calcification in 2620 male individuals who were current or former heavy smokers and underwent chest CT scans in the NELSON trial. No SNPs were associated with aortic calcification on a genome-wide scale. The 9p21 locus was significantly associated with coronary artery calcification (rs1537370). Subsequently, two loci at ADAMTS7 (rs3825807) and at PHACTR1 (rs12526453) showed a nominally significant association with coronary artery calcification and an increased degree of arterial calcification.[4]
## Clinical Marker
Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the PHACTR1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[13]
Another genome-wide association study in 2,326 clinic-based German and Dutch individuals with migraine without aura identified that PHACTR1 (together with ASTN2) as susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.[5][14][15] | https://www.wikidoc.org/index.php/PHACTR1 | |
1fb1b9b06eb2ab2091e3a29ac5b17df7577c6d46 | wikidoc | PIKFYVE | PIKFYVE
PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.
# Function
The principal enzymatic activity of PIKfyve is to phosphorylate PtdIns3P to PtdIns(3,5)P2. PIKfyve activity is responsible for the production of both PtdIns(3,5)P2 and phosphatidylinositol 5-phosphate (PtdIns5P). PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. The reported full-length mouse and human cDNA clones encode proteins of 2052 and 2098 amino acid residues, respectively. By directly binding membrane PtdIns(3)P, the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes. Impaired PIKfyve enzymatic activity by dominant-interfering mutants, siRNA- mediated ablation or pharmacological inhibition causes endosome enlargement and cytoplasmic vacuolation due to impaired PtdIns(3,5)P2 synthesis. Thus, via PtdIns(3,5)P2 production, PIKfyve participates in several aspects of endosome dynamics, thereby affecting a number of trafficking pathways that emanate from or traverse the endosomal system en route to the trans-Golgi network or later compartments along the endocytic pathway.
# Medical significance
PIKfyve mutations affecting one of the two PIKFYVE alleles are found in 8 out of 10 families with Francois-Neetens corneal fleck dystrophy. Disruption of both PIKFYVE alleles in the mouse is lethal at the stage of pre-implantation embryo. PIKfyve’s role in pathogen invasion is deduced by evidence from cell studies implicating PIKfyve activity in HIV and Salmonella replication. A link of PIKfyve with type 2 diabetes is inferred by the observations that PIKfyve perturbation inhibits insulin-regulated glucose uptake. Concordantly, mice with selective Pikfyve gene disruption in skeletal muscle, the tissue mainly responsible for the decrease of postprandial blood sugar, exhibit systemic insulin resistance; glucose intolerance; hyperinsulinemia; and increased adiposity, i.e. symptoms, typical for human prediabetes.
# Interactions
PIKfyve physically associates with its regulator ArPIKfyve, a protein encoded by the human gene VAC14, and the Sac1 domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by FIG4, to form a stable ternary heterooligomeric complex that is scaffolded by ArPIKfyve homooligomeric interactions. The presence of two enzymes with opposing activities for PtdIns(3,5)P2 synthesis and turnover in a single complex indicates the requirement for a tight control of PtdIns(3,5)P2 levels. PIKfyve also interacts with the Rab9 effector RABEPK and the kinesin adaptor JLP, encoded by SPAG9. These interactions link PIKfyve to microtubule-based endosome to trans-Golgi network traffic. Under sustained activation of glutamate receptors PIKfyve binds to and facilitates the lysosomal degradation of Cav1.2, voltage-dependent calcium channel type 1.2, thereby protecting the neurons from excitotoxicity. PIKfyve negatively regulates Ca2+-dependent exocytosis in neuroendocrine cells without affecting voltage-gated calcium channels.
# Evolutionary biology
PIKFYVE belongs to a large family of evolutionarily-conserved lipid kinases. Single copy genes, encoding similarly-structured FYVE-domain–containing phosphoinositide kinases exist in most genomes from yeast to man. The plant A. thaliana has several copies of the enzyme. Higher eukaryotes (after D. melanogaster), acquire an additional DEP domain. The S. cerevisiae enzyme Fab1p is required for PtdIns(3,5)P2 synthesis under basal conditions and in response to hyperosmotic shock. PtdIns5P, made by PIKfyve kinase activity in mammalian cells, is not detected in budding yeast. Yeast Fab1p associates with Vac14p (the ortholog of human ArPIKfyve) and Fig4p (the ortholog of Sac3). The yeast Fab1 complex also includes Vac7p and probably Atg18p, proteins that are not detected in the mammalian PIKfyve complex. S. cerevisiae could survive without Fab1. In contrast, the knockout of the FYVE domain-containing enzymes in A. thaliana, D. melanogaster, C. elegans and M. musculus leads to embryonic lethality indicating that the FYVE-domain–containing phosphoinositide kinases have become essential in embryonic development of multicellular organisms. Thus, in evolution, the FYVE-domain-containing phosphoinositide kinases retain several aspects of the structural organization, enzyme activity and protein interactions from budding yeast. In higher eukaryotes, the enzymes acquire one additional domain, a role in the production of PtdIns5P, a new set of interacting proteins and become essential in embryonic development. | PIKFYVE
PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.[1][2]
# Function
The principal enzymatic activity of PIKfyve is to phosphorylate PtdIns3P to PtdIns(3,5)P2. PIKfyve activity is responsible for the production of both PtdIns(3,5)P2 and phosphatidylinositol 5-phosphate (PtdIns5P).[3][4][5][6] PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. The reported full-length mouse and human cDNA clones encode proteins of 2052 and 2098 amino acid residues, respectively.[2][7][8][9] By directly binding membrane PtdIns(3)P,[10] the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes.[2][10] Impaired PIKfyve enzymatic activity by dominant-interfering mutants, siRNA- mediated ablation or pharmacological inhibition causes endosome enlargement and cytoplasmic vacuolation due to impaired PtdIns(3,5)P2 synthesis. Thus, via PtdIns(3,5)P2 production, PIKfyve participates in several aspects of endosome dynamics,[11][12] thereby affecting a number of trafficking pathways that emanate from or traverse the endosomal system en route to the trans-Golgi network or later compartments along the endocytic pathway.[13][14][15][16][17][18]
# Medical significance
PIKfyve mutations affecting one of the two PIKFYVE alleles are found in 8 out of 10 families with Francois-Neetens corneal fleck dystrophy.[19] Disruption of both PIKFYVE alleles in the mouse is lethal at the stage of pre-implantation embryo.[20] PIKfyve’s role in pathogen invasion is deduced by evidence from cell studies implicating PIKfyve activity in HIV and Salmonella replication.[16][21][22] A link of PIKfyve with type 2 diabetes is inferred by the observations that PIKfyve perturbation inhibits insulin-regulated glucose uptake.[23][24] Concordantly, mice with selective Pikfyve gene disruption in skeletal muscle, the tissue mainly responsible for the decrease of postprandial blood sugar, exhibit systemic insulin resistance; glucose intolerance; hyperinsulinemia; and increased adiposity, i.e. symptoms, typical for human prediabetes.[25]
# Interactions
PIKfyve physically associates with its regulator ArPIKfyve, a protein encoded by the human gene VAC14, and the Sac1 domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by FIG4, to form a stable ternary heterooligomeric complex that is scaffolded by ArPIKfyve homooligomeric interactions. The presence of two enzymes with opposing activities for PtdIns(3,5)P2 synthesis and turnover in a single complex indicates the requirement for a tight control of PtdIns(3,5)P2 levels.[12][26][27] PIKfyve also interacts with the Rab9 effector RABEPK and the kinesin adaptor JLP, encoded by SPAG9.[14][18] These interactions link PIKfyve to microtubule-based endosome to trans-Golgi network traffic. Under sustained activation of glutamate receptors PIKfyve binds to and facilitates the lysosomal degradation of Cav1.2, voltage-dependent calcium channel type 1.2, thereby protecting the neurons from excitotoxicity.[28] PIKfyve negatively regulates Ca2+-dependent exocytosis in neuroendocrine cells without affecting voltage-gated calcium channels.[29]
# Evolutionary biology
PIKFYVE belongs to a large family of evolutionarily-conserved lipid kinases. Single copy genes, encoding similarly-structured FYVE-domain–containing phosphoinositide kinases exist in most genomes from yeast to man. The plant A. thaliana has several copies of the enzyme. Higher eukaryotes (after D. melanogaster), acquire an additional DEP domain. The S. cerevisiae enzyme Fab1p is required for PtdIns(3,5)P2 synthesis under basal conditions and in response to hyperosmotic shock. PtdIns5P, made by PIKfyve kinase activity in mammalian cells, is not detected in budding yeast.[30] Yeast Fab1p associates with Vac14p (the ortholog of human ArPIKfyve) and Fig4p (the ortholog of Sac3).[31] The yeast Fab1 complex also includes Vac7p and probably Atg18p, proteins that are not detected in the mammalian PIKfyve complex.[32] S. cerevisiae could survive without Fab1.[33] In contrast, the knockout of the FYVE domain-containing enzymes in A. thaliana, D. melanogaster, C. elegans and M. musculus leads to embryonic lethality indicating that the FYVE-domain–containing phosphoinositide kinases have become essential in embryonic development of multicellular organisms.[20][34][35][36] Thus, in evolution, the FYVE-domain-containing phosphoinositide kinases retain several aspects of the structural organization, enzyme activity and protein interactions from budding yeast. In higher eukaryotes, the enzymes acquire one additional domain, a role in the production of PtdIns5P, a new set of interacting proteins and become essential in embryonic development. | https://www.wikidoc.org/index.php/PIKFYVE | |
c4c750e345256436e0201cdac918312295c70e19 | wikidoc | PIP4K2A | PIP4K2A
Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene.
# Function
Phosphatidylinositol-4,5-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family.
# Clinical Importance
Through genome wide association studies (GWAS), some of the single nucleotide polymorphisms (SNPs) located in this gene have been noticed to be significantly associated with susceptibility of childhood acute lymphoblastic leukaemia in ethnically diverse populations. | PIP4K2A
Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene.[1][2][3]
# Function
Phosphatidylinositol-4,5-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family.[3]
# Clinical Importance
Through genome wide association studies (GWAS), some of the single nucleotide polymorphisms (SNPs) located in this gene have been noticed to be significantly associated with susceptibility of childhood acute lymphoblastic leukaemia in ethnically diverse populations.[4][5] | https://www.wikidoc.org/index.php/PIP4K2A | |
eef3f3e97a9f07f2c0d8a8768e26620d2affda77 | wikidoc | PIP4K2B | PIP4K2B
Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the PIP4K2B gene.
The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor.
# Interactions
PIP4K2B has been shown to interact with TNFRSF1A. In addition, PIP4K2B has been shown to interact with PIP4K2A and may modulate the cellular localisation of PIP4K2A.
# Structure
The structure of PIP4K2B has been determined through X-ray crystallography. | PIP4K2B
Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the PIP4K2B gene.[1][2][3][4]
The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor.[4]
# Interactions
PIP4K2B has been shown to interact with TNFRSF1A.[1] In addition, PIP4K2B has been shown to interact with PIP4K2A and may modulate the cellular localisation of PIP4K2A.[5]
# Structure
The structure of PIP4K2B has been determined through X-ray crystallography.[6] | https://www.wikidoc.org/index.php/PIP4K2B | |
26a865f9a91c1bc5ab519e4e6cdf83b06e436309 | wikidoc | PIP5K1C | PIP5K1C
Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma is an enzyme that in humans is encoded by the PIP5K1C gene.
This gene encodes a member of the type I phosphatidylinositol-4-phosphate 5-kinase family of enzymes. A similar protein in mice is found in synapses and focal adhesion plaques, and binds the FERM domain of talin through its C-terminus.
# Model organisms
Model organisms have been used in the study of PIP5K1C function. A conditional knockout mouse line, called Pip5k1ctm1a(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 two significant abnormalities were observed. Fewer than expected homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and no further phenotypes were observed. | PIP5K1C
Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma is an enzyme that in humans is encoded by the PIP5K1C gene.[1][2]
This gene encodes a member of the type I phosphatidylinositol-4-phosphate 5-kinase family of enzymes. A similar protein in mice is found in synapses and focal adhesion plaques, and binds the FERM domain of talin through its C-terminus.[2]
# Model organisms
Model organisms have been used in the study of PIP5K1C function. A conditional knockout mouse line, called Pip5k1ctm1a(KOMP)Wtsi[7][8] 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.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty three tests were carried out on mutant mice and two significant abnormalities were observed.[5] Fewer than expected homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and no further phenotypes were observed.[5] | https://www.wikidoc.org/index.php/PIP5K1C | |
823091ddeed9f61145a78766df0ad867d812536a | wikidoc | PITPNM1 | PITPNM1
Membrane-associated phosphatidylinositol transfer protein 1 is a protein that in humans is encoded by the PITPNM1 gene.
# Function
PITPNM1 belongs to a family of proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein.
It was found that aggressive metastasized cancer cells produced more of the PITPNC1 protein. In contrast, tumor cells that had not spread had lower expression of PITPNC1. Studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3 (Golgi phosphoprotein 3), which facilitates Golgi extension and enhanced vesicular release. PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10.
# Interactions
PITPNM1 has been shown to interact with PTK2B. | PITPNM1
Membrane-associated phosphatidylinositol transfer protein 1 is a protein that in humans is encoded by the PITPNM1 gene.[1][2]
# Function
PITPNM1 belongs to a family of proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein.[supplied by OMIM][2]
It was found that aggressive metastasized cancer cells produced more of the PITPNC1 protein. In contrast, tumor cells that had not spread had lower expression of PITPNC1. Studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3 (Golgi phosphoprotein 3), which facilitates Golgi extension and enhanced vesicular release. PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10.[3]
# Interactions
PITPNM1 has been shown to interact with PTK2B.[4] | https://www.wikidoc.org/index.php/PITPNM1 |
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