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5944fb3f0213d575c6bf8094a9a782274a8a6883 | wikidoc | Optometry | Optometry
# Overview
Optometry (Greek: optos meaning seen or visible and metria meaning measurement) is a health care profession concerned with eyes and related structures, vision, visual system and vision information processing in humans.
Like most health professions, optometry education, certification and practice is regulated in most countries. Optometrists and related organizations interact with government, other health care professions and the community to deliver eyecare and visioncare. Optometry is a type of eyecare profession and optometrists often interact with other eye care professionals, such as ophthalmologists (medical doctors) and opticians.
# Scope of practice
Doctors of optometry (ODs), are primary health care professionals for the eye, serving patients in nearly 6,500 communities in the United States alone. Optometrists examine, diagnose, treat and manage diseases, injuries, and disorders of the visual system, the eye, and associated structures as well as identify related systemic conditions affecting the eye. Optometrists prescribe medications, low vision rehabilitation, vision therapy, spectacle lenses, and contact lenses. Optometrists can detect and diagnose eye diseases and disorders including glaucoma, cataracts and diabetic retinopathy. In all 50 of the United States, optometrists are licensed to prescribe medications to treat ocular diseases. Optometrists in Oklahoma may perform certain minor laser procedures.
## Eye & vision examination
As with most health care, examination often includes history taking and observations during tests.
- Examination of ocular health may include:
inspection of the external and internal ocular structures with various specialty equipment
-bservation of various eye movements and alignment
-bservation of pupillary reaction to light
- inspection of the external and internal ocular structures with various specialty equipment
- observation of various eye movements and alignment
- observation of pupillary reaction to light
- Examination of vision and visual function may include:
measurement of vision at distance and near
detailed refraction for distance and near with specialty equipment
measurement of optical aids such as glasses, contact lenses and magnifiers
measurement of stereopsis, colour vision screening, visual fields and other tests
- measurement of vision at distance and near
- detailed refraction for distance and near with specialty equipment
- measurement of optical aids such as glasses, contact lenses and magnifiers
- measurement of stereopsis, colour vision screening, visual fields and other tests
- Examination of visual skills:
applying a battery of structured visual tasks for patient to complete
- applying a battery of structured visual tasks for patient to complete
### Examples of equipment
There are many types of equipment used during an eye examination. For example, various vision charts and machines are used to measure vision and visual fields. Trial (spectacle & contact) lenses or a phoropter and retinoscope may be used during refraction. Prism bars, small objects and occluders may be used to assess eye movements and eye alignment. Penlight/transilluminator can be used when assessing pupil light response. Specialty magnifiers such as ophthalmoscope, and slit-lamp bio-microsope help with detailed inspection of external and internal ocular structures. Diagnostic eye drops may also be used to assess the eyes. Various test booklets/sheets/instructions and pencils may be used for visual information processing examination.
Another less common example of equipment used in optometry is Fresnel goggles which disables the patient from focusing, and thus is a tool to evaluate patients with Balance disorders
Recently many optometrists have began using equipment specifically designed to help treat certain diseases. For example, in states where O.D.'s are licensed to treat glaucoma you may find equipment that helps the O.D. to document a sick retina such as a Optical coherence tomography, GDX , or HRT II. Many offices have various visual field analyzers including a Humphrey Visual Field Analyzer.
## Diagnoses
Diagnoses made by optometry depends on integrating eye examination information.
Some ocular pathology can be associated with systemic, neural or other disease complications. Some ocular pathology and visual dysfunctions or disorders may require further specialty testing. Hence, referral may be required to refine diagnoses and/or to implement appropriate treatment.
- Some visual dysfunctions asessed by optometrists may include:
refractive error such as myopia, hyperopia, astigmatism and presbyopia
accommodative-vergence disorders (related to dynamic focus and eye alignment)
strabismus (squint or turned eye) and amblyopia (lazy eye)
- refractive error such as myopia, hyperopia, astigmatism and presbyopia
- accommodative-vergence disorders (related to dynamic focus and eye alignment)
- strabismus (squint or turned eye) and amblyopia (lazy eye)
- Some common examples of ocular pathology diagnosed by optometry:
cataract, macular degeneration, glaucoma, visual field loss
infection and inflammation of ocular structure(s)
haemorrhage of vascular supply to the eye (internal or external)
- cataract, macular degeneration, glaucoma, visual field loss
- infection and inflammation of ocular structure(s)
- haemorrhage of vascular supply to the eye (internal or external)
## Management
Optometry management can include:
- counsel regarding examination, diagnosis and management of ocular and visual findings
- prescribing medications, and perform certain surgical procedures (in some countries)
- prescribing optical aids such as glasses, contact lenses, magnifiers
- prescribing low vision rehabilitation
- prescribing vision therapy
- advice and follow-up care regarding use of optical aids (especially contact lenses)
- referral to other health professionals, often including medical doctors, and other eyecare professionals such as ophthalmologists and optometrists practicing sub-specialties
- interacting with opticians and the optical industry which manufacture the optical aids according to the prescription
# History
Optometric history is tied to the development of
- vision science (related areas of medicine, microbiology, neurology, physiology, psychology, etc)
- optics, optical aids
- optical instruments, imaging techniques
- other eye care professions
The term optometrists was coined by Landolt in 1886, referring to the "fitting of glasses". Prior to this, there was a distinction between "dispensing" and "refracting" opticians in the 19th century. The latter were later called optometrists.
Apparently the first schools of optometry were established in 1850-1900 (presumably in USA) and contact lenses were first used in 1940's
# Education and licensing
Most countries have regulations concerning optometry education and practice. Often, optometrists are required to participate in ongoing continuing education courses to stay current on the latest standards of care.
Optometry is officially recognized:
- in North America (Canada and US)
- in most English speaking countries including UK and Australia
- in Europe including Spain, Germany and France
- in Asia including Malaysia, China, Hong Kong, Thailand and Taiwan
- in the Middle East including Saudi Arabia and Iran
## United Kingdom
In the United Kingdom, optometrists have to complete a 3 or 4 year undergraduate honours degree followed by a minimum of a one-year "pre-registration period" where they complete supervised practice under the supervision of an experienced qualified practitioner. During this year the pre-registration candidate is given a number of quarterly assessments and on successfully passing all of these assessments, a final one-day set of examinations. Following successful completion of these assessments and having completed one year's supervised practice, the candidate qualifies for membership of The College of Optometrists and is eligible to register as an optometrist with the General Optical Council (GOC).
Registration with the GOC is mandatory to practice in the UK. Members of the College of Optometrists may use the suffix MCOptom. Optometrists in the United Kingdom, as in most countries except the United States and Canada, receive a Bachelor of Optometry or Masters degree. They are not called "doctor" in the United Kingdom.
## United States
As primary eye care providers, doctors of optometry are an integral part of the health care team, earning their doctoral degree just as dentists, podiatrists and other doctors do. Prior to admittance into optometry school, optometrists typically complete four years of undergraduate study, culminating in a bachelor’s degree. Required undergraduate coursework for pre-optometry students is extensive and covers a wide variety of advanced health, science and mathematics courses. Optometry school consists of four years of post-graduate, doctoral level study focusing on the eye, vision and associated systemic diseases. In addition to profession-specific courses, optometrists are required to take systemic health courses that focus on a patient’s overall medical condition as it relates to the eyes.
Upon completion of optometry school, candidates graduate from their accredited college of optometry and hold the doctor of optometry (OD) degree. Optometrists must pass a rigorous national examination administered by the National Board of Examiners in Optometry (NBEO). The three-part exam includes basic science, clinical science and patient care. Some optometrists go on to complete residencies with advanced training in a specific sub-specialty. These specialties can include pediatric care, children’s vision, geriatric care, pre- and post-surgery care, specialty contact lens (for keratoconus patients or other corneal dystrophies) and many others. All optometrists are required to participate in ongoing continuing education courses to stay current on the latest standards of care. Although optometry training in the United States is similar to that of the United Kingdom and many other countries, optometrists in the United States are among the few who are granted the degree of "Doctor of Optometry" instead of a bachelor's or master's degree in optometry.
## Europe
Currently, optometry education and licencing varies through out Europe. For example, in Germany, the tasks of an optometrist are split between ophthalmologists and professionally trained and certified opticians. In France, there is no regulatory framework and optometrists are sometimes trained by completing an apprenticeship at an ophthalmologists' private office.
Since the formation of the European Union, "there exists a strong movement, headed by the Association of European Schools and Colleges of Optometry (AESCO), to unify the profession by creating a European-wide examination for optometry" and presumably also standardised practice and education guidelines within EU countries.
# Distinction From Ophthalmology
Ophthalmologists complete a general medical degree (M.D.) at an accredited medical school, and an additional four years of postgraduate specialty medical and surgical training in ophthalmology. Ophthalmologists can manage ocular diseases (or ocular conditions) with medical and/or surgical treatments. Similar to optometry, there are also various sub-specialties within ophthalmology.
In addition to training with respect to medical conditions of the eyes and visual system, Optometry courses usually include many vision science subjects. Examples include courses in visual psychophysics, as well as training in aspects of functional vision such as vision therapy, binocular vision, and low vision. Ophthalmology training focuses more on dicks and medical and surgical management of ocular and systemic disease with less emphasis on functional vision. While both ophthalmologists and optometrists are trained in refraction, optometrists often receive more detailed training in prescribing optical aids such as spectacles and contact lenses. Hence optometrists are often more concerned with optical and vision therapy treatments.
The two fields often have a mutually beneficial relationship.
Ophthalmologists may refer patients to optometrists for optical aids or low vision rehabilitation whilst continuing to treat the ocular disease/condition that may have reduced vision.
Both optometrists and ophthalmologists perform screening for common ocular problems affecting children (i.e., amblyopia and strabismus) and the adult population (cataract, glaucoma, and diabetic retinopathy). Optometrists may refer to ophthalmology for further assessment and medical treatment of ocular disease or condition.
Optometrists and ophthalmologists sometimes co-manage treatment of strabismus and amblyopia with a combination of vision therapy, medical or surgical treatment.
See also Ophthalmology#Distinction_from_Optometry
# Sub-specialties
There are currently nine sub-specialty residencies offered by various schools of optometry in the United States :
- Cornea and contact lenses
- Family practice optometry
- Geriatric optometry
- Glaucoma
- Low vision rehabilitation
- Ocular disease
- Pediatric optometry
- Primary care
- Vision therapy and rehabilitation
Many of these sub-specialties are also recognised in other countries.
Please note, refractive surgery and ocular surgery fellowships involve learning how to co-manage patients before and after eye surgery. Similarly, ocular disease residencies involve co-management practice with other health professionals. Also the College of Optometrists in Vision Development provides certification for eye doctors in vision therapy, behavioral and developmental vision care, and "visual rehabilitation". Training in binocular vision and orthoptics sub-specialties are often integrated into either pediatric or vision therapy programs. | Optometry
# Overview
Optometry (Greek: optos meaning seen or visible and metria meaning measurement) is a health care profession concerned with eyes and related structures, vision, visual system and vision information processing in humans.
Like most health professions, optometry education, certification and practice is regulated in most countries. Optometrists and related organizations interact with government, other health care professions and the community to deliver eyecare and visioncare. Optometry is a type of eyecare profession and optometrists often interact with other eye care professionals, such as ophthalmologists (medical doctors) and opticians.
# Scope of practice
Doctors of optometry (ODs), are primary health care professionals for the eye, serving patients in nearly 6,500 communities in the United States alone. Optometrists examine, diagnose, treat and manage diseases, injuries, and disorders of the visual system, the eye, and associated structures as well as identify related systemic conditions affecting the eye. Optometrists prescribe medications, low vision rehabilitation, vision therapy, spectacle lenses, and contact lenses. Optometrists can detect and diagnose eye diseases and disorders including glaucoma, cataracts and diabetic retinopathy. In all 50 of the United States, optometrists are licensed to prescribe medications to treat ocular diseases. Optometrists in Oklahoma may perform certain minor laser procedures.
## Eye & vision examination
As with most health care, examination often includes history taking and observations during tests.
- Examination of ocular health may include:
inspection of the external and internal ocular structures with various specialty equipment
observation of various eye movements and alignment
observation of pupillary reaction to light
- inspection of the external and internal ocular structures with various specialty equipment
- observation of various eye movements and alignment
- observation of pupillary reaction to light
- Examination of vision and visual function may include:
measurement of vision at distance and near
detailed refraction for distance and near with specialty equipment
measurement of optical aids such as glasses, contact lenses and magnifiers
measurement of stereopsis, colour vision screening, visual fields and other tests
- measurement of vision at distance and near
- detailed refraction for distance and near with specialty equipment
- measurement of optical aids such as glasses, contact lenses and magnifiers
- measurement of stereopsis, colour vision screening, visual fields and other tests
- Examination of visual skills:
applying a battery of structured visual tasks for patient to complete
- applying a battery of structured visual tasks for patient to complete
### Examples of equipment
There are many types of equipment used during an eye examination. For example, various vision charts and machines are used to measure vision and visual fields. Trial (spectacle & contact) lenses or a phoropter and retinoscope may be used during refraction. Prism bars, small objects and occluders may be used to assess eye movements and eye alignment. Penlight/transilluminator can be used when assessing pupil light response. Specialty magnifiers such as ophthalmoscope, and slit-lamp bio-microsope help with detailed inspection of external and internal ocular structures. Diagnostic eye drops may also be used to assess the eyes. Various test booklets/sheets/instructions and pencils may be used for visual information processing examination.
Another less common example of equipment used in optometry is Fresnel goggles which disables the patient from focusing, and thus is a tool to evaluate patients with Balance disorders [1]
Recently many optometrists have began using equipment specifically designed to help treat certain diseases. For example, in states where O.D.'s are licensed to treat glaucoma you may find equipment that helps the O.D. to document a sick retina such as a Optical coherence tomography, GDX [2], or HRT II. Many offices have various visual field analyzers including a Humphrey Visual Field Analyzer.
## Diagnoses
Diagnoses made by optometry depends on integrating eye examination information.
Some ocular pathology can be associated with systemic, neural or other disease complications. Some ocular pathology and visual dysfunctions or disorders may require further specialty testing. Hence, referral may be required to refine diagnoses and/or to implement appropriate treatment.
- Some visual dysfunctions asessed by optometrists may include:
refractive error such as myopia, hyperopia, astigmatism and presbyopia
accommodative-vergence disorders (related to dynamic focus and eye alignment)
strabismus (squint or turned eye) and amblyopia (lazy eye)
- refractive error such as myopia, hyperopia, astigmatism and presbyopia
- accommodative-vergence disorders (related to dynamic focus and eye alignment)
- strabismus (squint or turned eye) and amblyopia (lazy eye)
- Some common examples of ocular pathology diagnosed by optometry:
cataract, macular degeneration, glaucoma, visual field loss
infection and inflammation of ocular structure(s)
haemorrhage of vascular supply to the eye (internal or external)
- cataract, macular degeneration, glaucoma, visual field loss
- infection and inflammation of ocular structure(s)
- haemorrhage of vascular supply to the eye (internal or external)
## Management
Optometry management can include:
- counsel regarding examination, diagnosis and management of ocular and visual findings
- prescribing medications, and perform certain surgical procedures (in some countries)
- prescribing optical aids such as glasses, contact lenses, magnifiers
- prescribing low vision rehabilitation
- prescribing vision therapy
- advice and follow-up care regarding use of optical aids (especially contact lenses)
- referral to other health professionals, often including medical doctors, and other eyecare professionals such as ophthalmologists and optometrists practicing sub-specialties
- interacting with opticians and the optical industry which manufacture the optical aids according to the prescription
# History
Optometric history is tied to the development of
- vision science (related areas of medicine, microbiology, neurology, physiology, psychology, etc)
- optics, optical aids
- optical instruments, imaging techniques
- other eye care professions
The term optometrists was coined by Landolt in 1886, referring to the "fitting of glasses". Prior to this, there was a distinction between "dispensing" and "refracting" opticians in the 19th century. The latter were later called optometrists. [3]
Apparently the first schools of optometry were established in 1850-1900 (presumably in USA) and contact lenses were first used in 1940's [4]
# Education and licensing
Most countries have regulations concerning optometry education and practice. Often, optometrists are required to participate in ongoing continuing education courses to stay current on the latest standards of care.
Optometry is officially recognized:
- in North America (Canada and US)
- in most English speaking countries including UK and Australia
- in Europe including Spain, Germany and France
- in Asia including Malaysia, China, Hong Kong, Thailand and Taiwan
- in the Middle East including Saudi Arabia and Iran
## United Kingdom
In the United Kingdom, optometrists have to complete a 3 or 4 year undergraduate honours degree followed by a minimum of a one-year "pre-registration period" where they complete supervised practice under the supervision of an experienced qualified practitioner. During this year the pre-registration candidate is given a number of quarterly assessments and on successfully passing all of these assessments, a final one-day set of examinations. Following successful completion of these assessments and having completed one year's supervised practice, the candidate qualifies for membership of The College of Optometrists and is eligible to register as an optometrist with the General Optical Council (GOC).
Registration with the GOC is mandatory to practice in the UK. Members of the College of Optometrists may use the suffix MCOptom. Optometrists in the United Kingdom, as in most countries except the United States and Canada, receive a Bachelor of Optometry or Masters degree. They are not called "doctor" in the United Kingdom.
## United States
As primary eye care providers, doctors of optometry are an integral part of the health care team, earning their doctoral degree just as dentists, podiatrists and other doctors do. Prior to admittance into optometry school, optometrists typically complete four years of undergraduate study, culminating in a bachelor’s degree. Required undergraduate coursework for pre-optometry students is extensive and covers a wide variety of advanced health, science and mathematics courses. Optometry school consists of four years of post-graduate, doctoral level study focusing on the eye, vision and associated systemic diseases. In addition to profession-specific courses, optometrists are required to take systemic health courses that focus on a patient’s overall medical condition as it relates to the eyes.
Upon completion of optometry school, candidates graduate from their accredited college of optometry and hold the doctor of optometry (OD) degree. Optometrists must pass a rigorous national examination administered by the National Board of Examiners in Optometry (NBEO). The three-part exam includes basic science, clinical science and patient care. Some optometrists go on to complete residencies with advanced training in a specific sub-specialty. These specialties can include pediatric care, children’s vision, geriatric care, pre- and post-surgery care, specialty contact lens (for keratoconus patients or other corneal dystrophies) and many others. All optometrists are required to participate in ongoing continuing education courses to stay current on the latest standards of care. Although optometry training in the United States is similar to that of the United Kingdom and many other countries, optometrists in the United States are among the few who are granted the degree of "Doctor of Optometry" instead of a bachelor's or master's degree in optometry.
## Europe
Currently, optometry education and licencing varies through out Europe. For example, in Germany, the tasks of an optometrist are split between ophthalmologists and professionally trained and certified opticians. In France, there is no regulatory framework and optometrists are sometimes trained by completing an apprenticeship at an ophthalmologists' private office. [5]
Since the formation of the European Union, "there exists a strong movement, headed by the Association of European Schools and Colleges of Optometry (AESCO), to unify the profession by creating a European-wide examination for optometry" and presumably also standardised practice and education guidelines within EU countries.[6]
# Distinction From Ophthalmology
Ophthalmologists complete a general medical degree (M.D.) at an accredited medical school, and an additional four years of postgraduate specialty medical and surgical training in ophthalmology. Ophthalmologists can manage ocular diseases (or ocular conditions) with medical and/or surgical treatments. Similar to optometry, there are also various sub-specialties within ophthalmology.
In addition to training with respect to medical conditions of the eyes and visual system, Optometry courses usually include many vision science subjects. Examples include courses in visual psychophysics, as well as training in aspects of functional vision such as vision therapy, binocular vision, and low vision. Ophthalmology training focuses more on dicks and medical and surgical management of ocular and systemic disease with less emphasis on functional vision. While both ophthalmologists and optometrists are trained in refraction, optometrists often receive more detailed training in prescribing optical aids such as spectacles and contact lenses. Hence optometrists are often more concerned with optical and vision therapy treatments.
The two fields often have a mutually beneficial relationship.
Ophthalmologists may refer patients to optometrists for optical aids or low vision rehabilitation whilst continuing to treat the ocular disease/condition that may have reduced vision.
Both optometrists and ophthalmologists perform screening for common ocular problems affecting children (i.e., amblyopia and strabismus) and the adult population (cataract, glaucoma, and diabetic retinopathy). Optometrists may refer to ophthalmology for further assessment and medical treatment of ocular disease or condition.
Optometrists and ophthalmologists sometimes co-manage treatment of strabismus and amblyopia with a combination of vision therapy, medical or surgical treatment.
See also Ophthalmology#Distinction_from_Optometry
# Sub-specialties
There are currently nine sub-specialty residencies offered by various schools of optometry in the United States [1] [2]:
- Cornea and contact lenses
- Family practice optometry
- Geriatric optometry
- Glaucoma
- Low vision rehabilitation
- Ocular disease
- Pediatric optometry
- Primary care
- Vision therapy and rehabilitation
Many of these sub-specialties are also recognised in other countries.
Please note, refractive surgery and ocular surgery fellowships involve learning how to co-manage patients before and after eye surgery. Similarly, ocular disease residencies involve co-management practice with other health professionals. Also the College of Optometrists in Vision Development provides certification for eye doctors in vision therapy, behavioral and developmental vision care, and "visual rehabilitation". Training in binocular vision and orthoptics sub-specialties are often integrated into either pediatric or vision therapy programs. | https://www.wikidoc.org/index.php/Optometrist | |
5e77e3a5a4d143c6fdbd8859269f57ccd4be833c | wikidoc | Radiology | Radiology
Assistant Editor-In-Chief: Anand Patel, MD
# Overview
Radiology is the medical specialty directing medical imaging technologies to diagnose and sometimes treat diseases. Originally it was the aspect of medical science dealing with the medical use of electromagnetic energy emitted by X-ray machines or other such radiation devices for the purpose of obtaining visual information as part of medical imaging. Radiology that involves use of x-ray is called roentgenology. Today, following extensive training, radiologists direct an array of imaging technologies (such as ultrasound, computed tomography (CT) and magnetic resonance imaging) to diagnose or treat disease. Interventional radiology is the performance of (usually minimally invasive) medical procedures with the guidance of imaging technologies. The acquisition of medical imaging is usually carried out by the radiographer or radiologic technologist.
Outside of the medical field, radiology also encompasses the examination of the inner structure of objects using X-rays or other penetrating radiation.
# History of radiology
Radiology began with Wilhelm Conrad Röntgen’s discovery of x-rays in 1895.It was such an important advance in medicine that within ten years radiology was being used all over the Western world. In 1901, Roentgen received the first Nobel Prize in Physics. In 1905 the first English book on chest radiography was published. During World War I, Maria Skłodowska-Curie pushed for the use of mobile radiography units for the treatment of wounded soldiers. She personally provided the radon tubes for the French Army. In 1920 the Society of Radiographers was formed. In 1924 Gilbert Stead published his Elementary Physics for medical and radiology students, helping bring radiology to the level of a generally recognized medical specialty. In 1937 a patient with leukemia was treated at the University of California, Berkeley in the first therapeutic use of radioactivity for cancer. Also in 1937, Joseph Gilbert Hamilton started to use radioactive iodine as a diagnostic and therapeutic agent in the treatment of thyroid disease.
# Subdivisions
As a medical specialty, radiology can be classified broadly into Diagnostic radiology and Therapeutic radiology.
- Diagnostic radiology is the interpretation of images of the human body to aid in the diagnosis or prognosis of disease. It is divided into subfields by anatomic location and in some cases method:
Chest radiology.
Abdominal & Pelvic radiology. Sometimes together termed "Body Imaging."
Interventional radiology uses imaging to guide therapeutic and angiographic procedures. Also known as Vascular & Interventional radiology.
Neuroradiology is the sub-specialty in the field of brain, spine, head, and neck imaging.
Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
Musculoskeletal radiology is the sub-specialty in the field of bone, joint, and muscular imaging.
Pediatric radiology.
Mammography.
Nuclear Medicine is a subdivision of radiology that uses radioisotopes in the characterization of lesions and disease processes, and often yields functional information.
- Chest radiology.
- Abdominal & Pelvic radiology. Sometimes together termed "Body Imaging."
- Interventional radiology uses imaging to guide therapeutic and angiographic procedures. Also known as Vascular & Interventional radiology.
- Neuroradiology is the sub-specialty in the field of brain, spine, head, and neck imaging.
Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
- Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
- Musculoskeletal radiology is the sub-specialty in the field of bone, joint, and muscular imaging.
- Pediatric radiology.
- Mammography.
- Nuclear Medicine is a subdivision of radiology that uses radioisotopes in the characterization of lesions and disease processes, and often yields functional information.
- A Radiologist is a specialty physician trained in all areas of diagnostic radiology. Specialty certification is earned through the American Board of Radiology (ABR).
Nuclear Medicine, Interventional radiology, Neuroradiology and Pediatric radiology have optional subspecialty Board qualifications under the American Board of Radiology.
Dedicated specialty certification in Nuclear Medicine alone can be earned as a non-radiologist physician through the American Board of Nuclear Medicine.
- Nuclear Medicine, Interventional radiology, Neuroradiology and Pediatric radiology have optional subspecialty Board qualifications under the American Board of Radiology.
- Dedicated specialty certification in Nuclear Medicine alone can be earned as a non-radiologist physician through the American Board of Nuclear Medicine.
- Therapeutic radiology utilizes radiation (radiation therapy) for therapy of diseases such as cancer.
While originally encompassed within radiology, radiation oncology is now a separate field.
Radiation Oncology specialty certification is earned through the American Board of Radiology.
- While originally encompassed within radiology, radiation oncology is now a separate field.
- Radiation Oncology specialty certification is earned through the American Board of Radiology.
# Acquisition of radiological images
Patients have the following procedures to provide images for Radiological decisions to be made.
## Projection radiography
Radiographs (or Roentgenographs, named after the discoverer of X-rays, Wilhelm Conrad Roentgen (1845-1923)) are often used for evaluation of bony structures and soft tissues. An X-Ray machine directs electromagnetic radiation upon a specified region in the body. This radiation tends to pass through less dense objects (skin, fat, muscle, and other tissues), but is absorbed or scattered by denser materials (bones, tumors, lungs affected by severe pneumonia). Radiation which has passed through a patient then strikes a cassette containing a screen of fluorescent phosphors and exposes x-ray film. Areas of film exposed to higher amounts of radiation will appear black or dark gray after development. The unexposed areas of film remain white. In Computed Radiography (CR), the x-ray photons are captured by phosphors within a cassette, which are then read-out by a scanning machine to give an electronic rendering of the image. In Digital Radiography (DR) the radiation strikes a plate of minute sensors yielding a digital image, which is then transmitted and stored by computer and viewed on a computer screen. In the U.S. all three modalities for obtaining images are currently in use, although the trend is away from film and toward digital imaging.
## Fluoroscopy
Fluoroscopy and angiography are special applications of X-ray imaging, in which a fluorescent screen or image intensifier tube is connected to a closed-circuit television system, which allows real-time imaging of structures in motion or augmented with a radiocontrast agent. Radiocontrast agents are administered, often swallowed or injected into the body of the patient, to delineate anatomy and functioning of the blood vessels, the genitourinary system or the gastrointestinal tract.Two radiocontrasts are presently in use. Barium (as BaSO4) may be given orally or rectally for evaluation of the GI tract. Iodine, in multiple proprietary forms, may be given by oral, rectal, intraarterial or intravenous routes.. These radiocontrast agents strongly absorb or scatter X-ray radiation, and in conjunction with the real-time imaging allows demonstration of dynamic processes, such as peristalsis in the digestive tract or blood flow in arteries and veins. Iodine contrast may also be concentrated in abnormal areas more or less than in normal tissues and make abnormalities (tumors, cysts, inflammation) more conspicuous. Additionally, in specific circumstances air can be used as a contrast agent for the gastrointestinal system and carbon dioxide can be used as a contrast agent in the venous system; in these cases, the contrast agent attenuates the X-ray radiation less than the surrounding tissues.
## CT scanning
CT imaging uses X-rays in conjunction with computing algorithms to image the body. In CT, an X-ray generating tube opposite an X-ray detector (or detectors) in a ring shaped apparatus rotate around a patient producing a computer generated cross-sectional image (tomogram). CT is acquired in the axial plane, while coronal and sagittal images can be rendered by computer reconstruction. Radiocontrast agents are often used with CT for enhanced delineation of anatomy. Intravenous contrast can allow 3D reconstructions of arteries and veins. Although radiographs provide higher spatial resolution, CT can detect more subtle variations in attenuation of X-rays. CT exposes the patient to more ionizing radiation than a radiograph. Spiral Multi-detector CT utilizes 8,16 or 64 detectors during continuous motion of the patient through the radiation beam to obtain much finer detail images in a shorter exam time. With computer manipulation these images can be reconstructed into 3D images of carotid, cerebral and coronary arteries. Faster scanning times in modern equipment has been associated with increased utilization.
## Ultrasound
Medical ultrasonography uses ultrasound (high-frequency sound waves) to visualize soft tissue structures in the body in real time. No ionizing radiation is involved, but the quality of the images obtained using ultrasound is highly dependent on the skill of the person (ultrasonographer) performing the exam. Ultrasound is also limited by its inability to image through air (lungs, bowel loops) or bone. The use of ultrasound in medical imaging has developed mostly within the last 30 years. The first ultrasound images were static and two dimensional (2D), but with modern-day ultrasonography 3D reconstructions can be observed in real-time; effectively becoming 4D.
Because ultrasound does not utilize ionizing radiation, unlike radiography, CT scans, and nuclear medicine imaging techniques, it is generally considered safer. For this reason, this modality plays a vital role in obstetrical imaging. Fetal anatomic development can be thoroughly evaluated allowing early diagnosis of many fetal anomalies. Growth can be assessed over time, important in patients with chronic disease or gestation-induced disease, and in multiple gestations (twins, triplets etc.). Color-Flow Doppler Ultrasound measures the severity of peripheral vascular disease and is used by Cardiology for dynamic evaluation of the heart, heart valves and major vessels. Stenosis of the carotid arteries can presage cerebral infarcts (strokes). DVT in the legs can be found via ultrasound before it dislodges and travels to the lungs (pulmonary embolism), which can be fatal if left untreated. Ultrasound is useful for image-guided interventions like biopsies and drainages such as thoracentesis). It is also used in the treatment of kidney stones (renal lithiasis) via lithotripsy. Small portable ultrasound devices now replace peritoneal lavage in the triage of trauma victims by directly assessing for the presence of hemorrhage in the peritoneum and the integrity of the major viscera including the liver, spleen and kidneys. Extensive hemoperitoneum (bleeding inside the body cavity) or injury to the major organs may require emergent surgical exploration and repair.
## MRI
MRI uses strong magnetic fields to align spinning atomic nuclei (usually hydrogen protons) within body tissues, then uses a radio signal to disturb the axis of rotation of these nuclei and observes the radio frequency signal generated as the nuclei return to their baseline states. The radio signals are collected by small antennae, called coils, placed near the area of interest. An advantage of MRI is its ability to produce images in axial, coronal, sagittal and multiple oblique planes with equal ease. MRI scans give the best soft tissue contrast of all the imaging modalities. With advances in scanning speed and spatial resolution, and improvements in computer 3D algorithms and hardware, MRI has become an essential tool in musculoskeltal radiology and neuroradiology.
One disadvantage is that the patient has to hold still for long periods of time in a noisy, cramped space while the imaging is performed. Claustrophobia severe enough to terminate the MRI exam is reported in up to 5% of patients. Recent improvements in magnet design including stronger magnetic fields (3 Tesla), shortening exam times, wider, shorter magnet bores and more open magnet designs, have brought some relief for claustrophobic patients. However, in magnets of equal field strength there is often a trade-off between image quality and open design. MRI has great benefit in imaging the brain, spine, and musculoskeletal system. The modality is currently contraindicated for patients with pacemakers, cochlear implants, some indwelling medication pumps, certain types of cerebral aneurysm clips, metal fragments in the eyes and some metallic hardware due to the powerful magnetic fields and strong fluctuating radio signals the body is exposed to. Areas of potential advancement include functional imaging, cardiovascular MRI, as well as MR image guided therapy.
# Nuclear medicine
Nuclear medicine imaging involves the administration into the patient of radiopharmaceuticals consisting of substances with affinity for certain body tissues labeled with radioactive tracer. The most commonly used tracers are Technetium-99m, Iodine-123, Iodine-131 and Xenon-133. The heart, lungs, thyroid, liver, gallbladder, and bones are commonly evaluated for particular conditions using these techniques. While anatomical detail is limited in these studies, nuclear medicine is useful in displaying physiological function. The excretory function of the kidneys, iodine concentrating ability of the thyroid, blood flow to heart muscle, etc. can be measured. The principal imaging device is the gamma camera which detects the radiation emitted by the tracer in the body and displays it as an image. With computer processing, the information can be displayed as axial, coronal and sagittal images (SPECT images). In the most modern devices Nuclear Medicine images can be fused with a CT scan taken quasi-simultaneously so that the physiological information can be overlayed or co-registered with the anatomical structures to improve diagnostic accuracy.
PET scanning also falls under "nuclear medicine."In PET scanning, a radioactive biologically-active substance (most often Glucose-18) is injected into a patient and the radiation emitted by the patient is detected to produce multi-planar images of the body. Metabolically more active tissues, such as cancer, concentrate the active substance more than normal tissues. PET images can be combined with CT images to improve diagnostic accuracy.
The applications of nuclear medicine can include bone scanning which traditionally has had a strong role in the work-up/staging of cancers. Myocardial perfusion imaging is a sensitive and specific screening exam for reversible myocardial ischemia, which when present requires angiographic confirmation and potentially life-saving balloon angioplasty, stenting or cardiac bypass grafting. Molecular Imaging is the new and exciting frontier in this field.
# Radiologist training
## United States
Diagnostic radiologists must complete prerequisite undergraduate training, four years of medical school, and five years of post-graduate training. The first postgraduate year is usually a transitional year of various rotations, but is sometimes a preliminary internship in medicine or surgery. A four-year diagnostic radiology residency follows. After successful completion of their residency, the new radiologist is eligible to take board examinations (written and oral) given by the American Board of Radiology.
Following completion of residency training, radiologists either begin their practice or enter into sub-speciality training programs known as fellowships. Examples of sub-speciality training in radiology include abdominal imaging, thoracic imaging, MRI, musculoskeletal imaging, interventional radiology, neuroradiology, interventional neuroradiology, pediatric radiology, and women's imaging. Fellowship training programs in radiology are usually 1 or 2 years in length.
Radiology is currently considered a highly competitive field. Radiologists generally enjoy good compensation as well as a good balance between time required at work and time spent away from work. The field is rapidly expanding due to advances in computer technology which is closely linked to modern imaging.
The exams (radiography) are usually performed by radiologic technologists, (also known as diagnostic radiographers) who in the United States have a 2-year Associates Degree and the UK a 3 year Honours Degree.
Veterinary radiologists are veterinarians that specialize in the use of X-rays, ultrasound, MRI and nuclear medicine for diagnostic imaging or treatment of disease in animals. Veterinary radiologists are certified in either diagnostic radiology or radiation oncology by the American College of Veterinary Radiology.
## Australia and New Zealand
Radiology training begins after completion of medical degree (6 years) and at least 2 years of hospital residency (internship and junior house medical officer (JHMO) ). It then comprises 5 years , one of which can be a fellowship.
# Diagnostic radiology
Commonly used imaging modalities include plain radiography (X-rays), flouroscopy, mammography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear imaging techniques. These techniques are usually non-invasive. Each of these modalities has strengths and limitations which dictate its use in diagnosis. | Radiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Assistant Editor-In-Chief: Anand Patel, MD [2]
# Overview
Radiology is the medical specialty directing medical imaging technologies to diagnose and sometimes treat diseases. Originally it was the aspect of medical science dealing with the medical use of electromagnetic energy emitted by X-ray machines or other such radiation devices for the purpose of obtaining visual information as part of medical imaging. Radiology that involves use of x-ray is called roentgenology. Today, following extensive training, radiologists direct an array of imaging technologies (such as ultrasound, computed tomography (CT) and magnetic resonance imaging) to diagnose or treat disease. Interventional radiology is the performance of (usually minimally invasive) medical procedures with the guidance of imaging technologies. The acquisition of medical imaging is usually carried out by the radiographer or radiologic technologist.
Outside of the medical field, radiology also encompasses the examination of the inner structure of objects using X-rays or other penetrating radiation.
# History of radiology
Radiology began with Wilhelm Conrad Röntgen’s discovery of x-rays in 1895.It was such an important advance in medicine that within ten years radiology was being used all over the Western world. In 1901, Roentgen received the first Nobel Prize in Physics. In 1905 the first English book on chest radiography was published. During World War I, Maria Skłodowska-Curie pushed for the use of mobile radiography units for the treatment of wounded soldiers. She personally provided the radon tubes for the French Army. In 1920 the Society of Radiographers was formed. In 1924 Gilbert Stead published his Elementary Physics for medical and radiology students, helping bring radiology to the level of a generally recognized medical specialty. In 1937 a patient with leukemia was treated at the University of California, Berkeley in the first therapeutic use of radioactivity for cancer. Also in 1937, Joseph Gilbert Hamilton started to use radioactive iodine as a diagnostic and therapeutic agent in the treatment of thyroid disease.
# Subdivisions
As a medical specialty, radiology can be classified broadly into Diagnostic radiology and Therapeutic radiology.
- Diagnostic radiology is the interpretation of images of the human body to aid in the diagnosis or prognosis of disease. It is divided into subfields by anatomic location and in some cases method:
Chest radiology.
Abdominal & Pelvic radiology. Sometimes together termed "Body Imaging."
Interventional radiology uses imaging to guide therapeutic and angiographic procedures. Also known as Vascular & Interventional radiology.
Neuroradiology is the sub-specialty in the field of brain, spine, head, and neck imaging.
Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
Musculoskeletal radiology is the sub-specialty in the field of bone, joint, and muscular imaging.
Pediatric radiology.
Mammography.
Nuclear Medicine is a subdivision of radiology that uses radioisotopes in the characterization of lesions and disease processes, and often yields functional information.
- Chest radiology.
- Abdominal & Pelvic radiology. Sometimes together termed "Body Imaging."
- Interventional radiology uses imaging to guide therapeutic and angiographic procedures. Also known as Vascular & Interventional radiology.
- Neuroradiology is the sub-specialty in the field of brain, spine, head, and neck imaging.
Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
- Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine.
- Musculoskeletal radiology is the sub-specialty in the field of bone, joint, and muscular imaging.
- Pediatric radiology.
- Mammography.
- Nuclear Medicine is a subdivision of radiology that uses radioisotopes in the characterization of lesions and disease processes, and often yields functional information.
- A Radiologist is a specialty physician trained in all areas of diagnostic radiology. Specialty certification is earned through the American Board of Radiology (ABR).
Nuclear Medicine, Interventional radiology, Neuroradiology and Pediatric radiology have optional subspecialty Board qualifications under the American Board of Radiology.
Dedicated specialty certification in Nuclear Medicine alone can be earned as a non-radiologist physician through the American Board of Nuclear Medicine.
- Nuclear Medicine, Interventional radiology, Neuroradiology and Pediatric radiology have optional subspecialty Board qualifications under the American Board of Radiology.
- Dedicated specialty certification in Nuclear Medicine alone can be earned as a non-radiologist physician through the American Board of Nuclear Medicine.
- Therapeutic radiology utilizes radiation (radiation therapy) for therapy of diseases such as cancer.
While originally encompassed within radiology, radiation oncology is now a separate field.
Radiation Oncology specialty certification is earned through the American Board of Radiology.
- While originally encompassed within radiology, radiation oncology is now a separate field.
- Radiation Oncology specialty certification is earned through the American Board of Radiology.
# Acquisition of radiological images
Patients have the following procedures to provide images for Radiological decisions to be made.
## Projection radiography
Radiographs (or Roentgenographs, named after the discoverer of X-rays, Wilhelm Conrad Roentgen (1845-1923)) are often used for evaluation of bony structures and soft tissues. An X-Ray machine directs electromagnetic radiation upon a specified region in the body. This radiation tends to pass through less dense objects (skin, fat, muscle, and other tissues), but is absorbed or scattered by denser materials (bones, tumors, lungs affected by severe pneumonia). Radiation which has passed through a patient then strikes a cassette containing a screen of fluorescent phosphors and exposes x-ray film. Areas of film exposed to higher amounts of radiation will appear black or dark gray after development. The unexposed areas of film remain white. In Computed Radiography (CR), the x-ray photons are captured by phosphors within a cassette, which are then read-out by a scanning machine to give an electronic rendering of the image. In Digital Radiography (DR) the radiation strikes a plate of minute sensors yielding a digital image, which is then transmitted and stored by computer and viewed on a computer screen. In the U.S. all three modalities for obtaining images are currently in use, although the trend is away from film and toward digital imaging.
## Fluoroscopy
Fluoroscopy and angiography are special applications of X-ray imaging, in which a fluorescent screen or image intensifier tube is connected to a closed-circuit television system, which allows real-time imaging of structures in motion or augmented with a radiocontrast agent. Radiocontrast agents are administered, often swallowed or injected into the body of the patient, to delineate anatomy and functioning of the blood vessels, the genitourinary system or the gastrointestinal tract.Two radiocontrasts are presently in use. Barium (as BaSO4) may be given orally or rectally for evaluation of the GI tract. Iodine, in multiple proprietary forms, may be given by oral, rectal, intraarterial or intravenous routes.. These radiocontrast agents strongly absorb or scatter X-ray radiation, and in conjunction with the real-time imaging allows demonstration of dynamic processes, such as peristalsis in the digestive tract or blood flow in arteries and veins. Iodine contrast may also be concentrated in abnormal areas more or less than in normal tissues and make abnormalities (tumors, cysts, inflammation) more conspicuous. Additionally, in specific circumstances air can be used as a contrast agent for the gastrointestinal system and carbon dioxide can be used as a contrast agent in the venous system; in these cases, the contrast agent attenuates the X-ray radiation less than the surrounding tissues.
## CT scanning
CT imaging uses X-rays in conjunction with computing algorithms to image the body. In CT, an X-ray generating tube opposite an X-ray detector (or detectors) in a ring shaped apparatus rotate around a patient producing a computer generated cross-sectional image (tomogram). CT is acquired in the axial plane, while coronal and sagittal images can be rendered by computer reconstruction. Radiocontrast agents are often used with CT for enhanced delineation of anatomy. Intravenous contrast can allow 3D reconstructions of arteries and veins. Although radiographs provide higher spatial resolution, CT can detect more subtle variations in attenuation of X-rays. CT exposes the patient to more ionizing radiation than a radiograph. Spiral Multi-detector CT utilizes 8,16 or 64 detectors during continuous motion of the patient through the radiation beam to obtain much finer detail images in a shorter exam time. With computer manipulation these images can be reconstructed into 3D images of carotid, cerebral and coronary arteries. Faster scanning times in modern equipment has been associated with increased utilization.
## Ultrasound
Medical ultrasonography uses ultrasound (high-frequency sound waves) to visualize soft tissue structures in the body in real time. No ionizing radiation is involved, but the quality of the images obtained using ultrasound is highly dependent on the skill of the person (ultrasonographer) performing the exam. Ultrasound is also limited by its inability to image through air (lungs, bowel loops) or bone. The use of ultrasound in medical imaging has developed mostly within the last 30 years. The first ultrasound images were static and two dimensional (2D), but with modern-day ultrasonography 3D reconstructions can be observed in real-time; effectively becoming 4D.
Because ultrasound does not utilize ionizing radiation, unlike radiography, CT scans, and nuclear medicine imaging techniques, it is generally considered safer. For this reason, this modality plays a vital role in obstetrical imaging. Fetal anatomic development can be thoroughly evaluated allowing early diagnosis of many fetal anomalies. Growth can be assessed over time, important in patients with chronic disease or gestation-induced disease, and in multiple gestations (twins, triplets etc.). Color-Flow Doppler Ultrasound measures the severity of peripheral vascular disease and is used by Cardiology for dynamic evaluation of the heart, heart valves and major vessels. Stenosis of the carotid arteries can presage cerebral infarcts (strokes). DVT in the legs can be found via ultrasound before it dislodges and travels to the lungs (pulmonary embolism), which can be fatal if left untreated. Ultrasound is useful for image-guided interventions like biopsies and drainages such as thoracentesis). It is also used in the treatment of kidney stones (renal lithiasis) via lithotripsy. Small portable ultrasound devices now replace peritoneal lavage in the triage of trauma victims by directly assessing for the presence of hemorrhage in the peritoneum and the integrity of the major viscera including the liver, spleen and kidneys. Extensive hemoperitoneum (bleeding inside the body cavity) or injury to the major organs may require emergent surgical exploration and repair.
## MRI
MRI uses strong magnetic fields to align spinning atomic nuclei (usually hydrogen protons) within body tissues, then uses a radio signal to disturb the axis of rotation of these nuclei and observes the radio frequency signal generated as the nuclei return to their baseline states. The radio signals are collected by small antennae, called coils, placed near the area of interest. An advantage of MRI is its ability to produce images in axial, coronal, sagittal and multiple oblique planes with equal ease. MRI scans give the best soft tissue contrast of all the imaging modalities. With advances in scanning speed and spatial resolution, and improvements in computer 3D algorithms and hardware, MRI has become an essential tool in musculoskeltal radiology and neuroradiology.
One disadvantage is that the patient has to hold still for long periods of time in a noisy, cramped space while the imaging is performed. Claustrophobia severe enough to terminate the MRI exam is reported in up to 5% of patients. Recent improvements in magnet design including stronger magnetic fields (3 Tesla), shortening exam times, wider, shorter magnet bores and more open magnet designs, have brought some relief for claustrophobic patients. However, in magnets of equal field strength there is often a trade-off between image quality and open design. MRI has great benefit in imaging the brain, spine, and musculoskeletal system. The modality is currently contraindicated for patients with pacemakers, cochlear implants, some indwelling medication pumps, certain types of cerebral aneurysm clips, metal fragments in the eyes and some metallic hardware due to the powerful magnetic fields and strong fluctuating radio signals the body is exposed to. Areas of potential advancement include functional imaging, cardiovascular MRI, as well as MR image guided therapy.
# Nuclear medicine
Nuclear medicine imaging involves the administration into the patient of radiopharmaceuticals consisting of substances with affinity for certain body tissues labeled with radioactive tracer. The most commonly used tracers are Technetium-99m, Iodine-123, Iodine-131 and Xenon-133. The heart, lungs, thyroid, liver, gallbladder, and bones are commonly evaluated for particular conditions using these techniques. While anatomical detail is limited in these studies, nuclear medicine is useful in displaying physiological function. The excretory function of the kidneys, iodine concentrating ability of the thyroid, blood flow to heart muscle, etc. can be measured. The principal imaging device is the gamma camera which detects the radiation emitted by the tracer in the body and displays it as an image. With computer processing, the information can be displayed as axial, coronal and sagittal images (SPECT images). In the most modern devices Nuclear Medicine images can be fused with a CT scan taken quasi-simultaneously so that the physiological information can be overlayed or co-registered with the anatomical structures to improve diagnostic accuracy.
PET scanning also falls under "nuclear medicine."In PET scanning, a radioactive biologically-active substance (most often Glucose-18) is injected into a patient and the radiation emitted by the patient is detected to produce multi-planar images of the body. Metabolically more active tissues, such as cancer, concentrate the active substance more than normal tissues. PET images can be combined with CT images to improve diagnostic accuracy.
The applications of nuclear medicine can include bone scanning which traditionally has had a strong role in the work-up/staging of cancers. Myocardial perfusion imaging is a sensitive and specific screening exam for reversible myocardial ischemia, which when present requires angiographic confirmation and potentially life-saving balloon angioplasty, stenting or cardiac bypass grafting. Molecular Imaging is the new and exciting frontier in this field.
# Radiologist training
## United States
Diagnostic radiologists must complete prerequisite undergraduate training, four years of medical school, and five years of post-graduate training. The first postgraduate year is usually a transitional year of various rotations, but is sometimes a preliminary internship in medicine or surgery. A four-year diagnostic radiology residency follows. After successful completion of their residency, the new radiologist is eligible to take board examinations (written and oral) given by the American Board of Radiology.
Following completion of residency training, radiologists either begin their practice or enter into sub-speciality training programs known as fellowships. Examples of sub-speciality training in radiology include abdominal imaging, thoracic imaging, MRI, musculoskeletal imaging, interventional radiology, neuroradiology, interventional neuroradiology, pediatric radiology, and women's imaging. Fellowship training programs in radiology are usually 1 or 2 years in length.
Radiology is currently considered a highly competitive field. Radiologists generally enjoy good compensation as well as a good balance between time required at work and time spent away from work. The field is rapidly expanding due to advances in computer technology which is closely linked to modern imaging.
The exams (radiography) are usually performed by radiologic technologists, (also known as diagnostic radiographers) who in the United States have a 2-year Associates Degree and the UK a 3 year Honours Degree.
Veterinary radiologists are veterinarians that specialize in the use of X-rays, ultrasound, MRI and nuclear medicine for diagnostic imaging or treatment of disease in animals. Veterinary radiologists are certified in either diagnostic radiology or radiation oncology by the American College of Veterinary Radiology.
## Australia and New Zealand
Radiology training begins after completion of medical degree (6 years) and at least 2 years of hospital residency (internship and junior house medical officer (JHMO) ). It then comprises 5 years , one of which can be a fellowship.
# Diagnostic radiology
Commonly used imaging modalities include plain radiography (X-rays), flouroscopy, mammography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear imaging techniques. These techniques are usually non-invasive. Each of these modalities has strengths and limitations which dictate its use in diagnosis. | https://www.wikidoc.org/index.php/Oral_and_Maxillofacial_Radiology | |
06b67d9b16442d2d5ca0830542b8235b3d456f78 | wikidoc | Orbivirus | Orbivirus
African horse sickness virus
Bluetongue virus
Epizootic hemorrhagic disease of deer virus
Equine encephalosis virus
Ibaraki virus
Palyam virus
The genus Orbivirus is a member of the Reoviridae family. This genus contains 19 species and at least 130 different serotypes. Orbiviruses can infect and replicate within a wide range of arthropod and vertebrate hosts.
# Virus Particles
Orbiviruses are named after their characteristic doughnut shaped capsomers (In Latin Orbi means ring). They have non-enveloped particles that are between 70-80nm in diameter. The virus particles are spherical in appearance and have icosahedral symmetry. An outer and an inner capsid layer surround the genome.
# Genome
These viruses have double stranded RNA genomes and therefore are classified as Class III viruses. Their genome is linear and is segmented into 10 segments of various lengths. One copy of each gene segment is packaged per virion. In most cases each gene segment encodes a single open reading frame (ORF).
# Replication
Many Orbiviruses preferentially infect vascular endothelial cells. Orbiviruses enter the host cell by endocytosis and the outer capsid is subsequently removed. The whole cycle of viral replication takes place within the cytoplasm of the host cell. Transcription of the viral genome into mRNA occurs within the core particle and mRNA is translated into proteins using the host cell ribosomes. Viral proteins are synthesized 2-14 days after initial infection. New virons self-assemble within the cytoplasm and are then released from the host cell by budding. During the budding process they transiently acquire a lipid envelope which can be detected for a short period of time following their release but this is subsequently lost.
# Pathogenesis
Orbiviruses primarily cause diseases in animals. The different Orbivirus species have different host specificities. Orbiviruses are vector-borne pathogens transmitted between vertebrate hosts by vectors such as mosquitoes, midges, gnats, sandflies and ticks. Bluetongue virus (BTV) is an Orbivirus that causes bluetongue disease in sheep, cattle, goats and wild ungulates. BTV has been in the forefront of molecular studies for last three decades and now represents one of the best understood viruses at the molecular and structural levels. Other species of Orbiviruses are responsible for other diseases of animals such as African Horse sickness and Colorado Tick Fever. | Orbivirus
Template:Taxobox begin
Template:Taxobox begin placement virus
Template:Taxobox group iii entry
Template:Taxobox familia entry
Template:Taxobox genus entry
Template:Taxobox end placement
Template:Taxobox section subdivision
African horse sickness virus
Bluetongue virus
Epizootic hemorrhagic disease of deer virus
Equine encephalosis virus
Ibaraki virus
Palyam virus
Template:Taxobox end
The genus Orbivirus is a member of the Reoviridae family. This genus contains 19 species and at least 130 different serotypes. Orbiviruses can infect and replicate within a wide range of arthropod and vertebrate hosts.
# Virus Particles
Orbiviruses are named after their characteristic doughnut shaped capsomers (In Latin Orbi means ring). They have non-enveloped particles that are between 70-80nm in diameter. The virus particles are spherical in appearance and have icosahedral symmetry. An outer and an inner capsid layer surround the genome.
# Genome
These viruses have double stranded RNA genomes and therefore are classified as Class III viruses. Their genome is linear and is segmented into 10 segments of various lengths. One copy of each gene segment is packaged per virion. In most cases each gene segment encodes a single open reading frame (ORF).
# Replication
Many Orbiviruses preferentially infect vascular endothelial cells. Orbiviruses enter the host cell by endocytosis and the outer capsid is subsequently removed. The whole cycle of viral replication takes place within the cytoplasm of the host cell. Transcription of the viral genome into mRNA occurs within the core particle and mRNA is translated into proteins using the host cell ribosomes. Viral proteins are synthesized 2-14 days after initial infection. New virons self-assemble within the cytoplasm and are then released from the host cell by budding. During the budding process they transiently acquire a lipid envelope which can be detected for a short period of time following their release but this is subsequently lost.
# Pathogenesis
Orbiviruses primarily cause diseases in animals. The different Orbivirus species have different host specificities. Orbiviruses are vector-borne pathogens transmitted between vertebrate hosts by vectors such as mosquitoes, midges, gnats, sandflies and ticks. Bluetongue virus (BTV) is an Orbivirus that causes bluetongue disease in sheep, cattle, goats and wild ungulates. BTV has been in the forefront of molecular studies for last three decades and now represents one of the best understood viruses at the molecular and structural levels.[1] [2] Other species of Orbiviruses are responsible for other diseases of animals such as African Horse sickness and Colorado Tick Fever. | https://www.wikidoc.org/index.php/Orbivirus | |
76a323b2afb18ca37d8c726a7cf4dd861f285855 | wikidoc | Organelle | Organelle
In cell biology, an organelle is a discrete structure of a cell having specialized functions, and is separately enclosed in its own lipid membrane. There are many types of organelles, particularly in the eukaryotic cells of higher organisms. Prokaryotes were once thought not to have any organelles, but some examples have now been identified, although these are not widespread.
The name organelle comes from the idea that these structures are to cells what an organ is to the body (hence the name organelle, the suffix -elle being a diminutive). Organelles are identified through the use of microscopy, and can also be identified by cell fractionation.
# Examples and disputes
Some cell biologists consider the term organelle to be synonymous with "cell compartment", other cell biologists strictly limit the term's definition to DNA-containing, formerly autonomous organisms acquired via primary, secondary, or tertiary endosymbiosis. A few of such large organelles having originated from endosymbiont bacteria:
- mitochondria (in almost all eukaryotes)
- plastids (in plants, algae and protists)
chloroplasts (mature forms of etioplasts)
chromoplasts
leucoplasts
amyloplasts
statoliths
elaioplasts
proteinoplasts
rhodoplasts (in red algae)
apicoplasts (in the malaria parasite, Plasmodium falciparum)
- chloroplasts (mature forms of etioplasts)
- chromoplasts
- leucoplasts
amyloplasts
statoliths
elaioplasts
proteinoplasts
- amyloplasts
statoliths
- statoliths
- elaioplasts
- proteinoplasts
- rhodoplasts (in red algae)
- apicoplasts (in the malaria parasite, Plasmodium falciparum)
Other organelles are also suggested to have endosymbiotic origins (notably the flagellum; see evolution of flagella), but these hypotheses are not widely accepted nor phylogenetically verified.
Not all parts of the cell qualify as organelles, and the use of the term to refer to some structures is disputed. These structures are large assemblies of macromolecules that carry out particular and specialised functions, but they lack membranes boundaries. Such cell structures, which are likely not organelles, include:
- ribosome
- cytoskeleton
- flagellum
# Eukaryotic Cells
Eukaryotes are the most structurally complex known cell type, and by definition are in part organized by smaller interior compartments, that are themselves enclosed by lipid membranes that resemble the outermost cell membrane. Eukaryotic cells include animal, plants, fungi, etc. They have membrane-bound organelles. The larger organelles, such as the nucleus and vacuoles, are easily visible with moderate magnification (although sometimes a clear view requires the application of chemicals that selectively stain parts of the cells); they were among the first biological discoveries made after the invention of the microscope.
Not all eukaryotic cells have all of the organelles listed below, and occasionally, exceptional species of cells are missing organelles which might otherwise be considered universal to eukaryotic cells (such as mitochondria). There are also occasional exceptions to the number of membranes surrounding organelles, listed in the tables below (e.g. some which are listed as double-membraned are sometimes found with single or triple membranes). In addition to this, the amount of the individual organelles varies depending upon the function of the specific cell to which it is found (example, muscle cells have more smooth endoplasmic reticulum which helps in muscle contraction)
Organelles which have double-membranes and their own DNA are believed by many biologists of having originally come from incompletely consumed or invading prokaryotic cells, which were adopted as a part of the invaded cell through endosymbiosis. Originally, the word organelle referred to large lipid-encased formerly autonomous endosymbiont within cells. As other intracellular compartments were discovered, the meaning was generalized (in the United States, mainly) to include any lipid-encased intracellular component with a specialized biochemical function.
Other related structures:
- cytosol
- endomembrane system
- nucleosome
- microtubule
- cell membrane
# Prokaryotic Cells
Prokaryotes are not as structurally complex as eukaryotes, and were thought not to have any compartments enclosed by lipid membranes. All bacterias are prokaryotic cells. They do not have membrane-bound organelles. In the past they were often viewed as having little internal organization, but slowly details are emerging about prokaryotic internal structures. One contributing discovery was that at least some prokaryotes have microcompartments, which are compartments enclosed by proteins. Even more striking is the description of prokaryotic organelles, such as magnetosomes, as well as the nucleus-like organelles of the Planctomycetes that are surrounded by lipid membranes. | Organelle
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In cell biology, an organelle is a discrete structure of a cell having specialized functions, and is separately enclosed in its own lipid membrane. There are many types of organelles, particularly in the eukaryotic cells of higher organisms. Prokaryotes were once thought not to have any organelles, but some examples have now been identified, although these are not widespread.
The name organelle comes from the idea that these structures are to cells what an organ is to the body (hence the name organelle, the suffix -elle being a diminutive). Organelles are identified through the use of microscopy, and can also be identified by cell fractionation.
# Examples and disputes
Some cell biologists consider the term organelle to be synonymous with "cell compartment", other cell biologists strictly limit the term's definition to DNA-containing, formerly autonomous organisms acquired via primary, secondary, or tertiary endosymbiosis. A few of such large organelles having originated from endosymbiont bacteria:
- mitochondria (in almost all eukaryotes)
- plastids (in plants, algae and protists)
chloroplasts (mature forms of etioplasts)
chromoplasts
leucoplasts
amyloplasts
statoliths
elaioplasts
proteinoplasts
rhodoplasts (in red algae)
apicoplasts (in the malaria parasite, Plasmodium falciparum)
- chloroplasts (mature forms of etioplasts)
- chromoplasts
- leucoplasts
amyloplasts
statoliths
elaioplasts
proteinoplasts
- amyloplasts
statoliths
- statoliths
- elaioplasts
- proteinoplasts
- rhodoplasts (in red algae)
- apicoplasts (in the malaria parasite, Plasmodium falciparum)
Other organelles are also suggested to have endosymbiotic origins (notably the flagellum; see evolution of flagella), but these hypotheses are not widely accepted nor phylogenetically verified.
Not all parts of the cell qualify as organelles, and the use of the term to refer to some structures is disputed. These structures are large assemblies of macromolecules that carry out particular and specialised functions, but they lack membranes boundaries. Such cell structures, which are likely not organelles, include:
- ribosome
- cytoskeleton
- flagellum
# Eukaryotic Cells
Eukaryotes are the most structurally complex known cell type, and by definition are in part organized by smaller interior compartments, that are themselves enclosed by lipid membranes that resemble the outermost cell membrane. Eukaryotic cells include animal, plants, fungi, etc. They have membrane-bound organelles. The larger organelles, such as the nucleus and vacuoles, are easily visible with moderate magnification (although sometimes a clear view requires the application of chemicals that selectively stain parts of the cells); they were among the first biological discoveries made after the invention of the microscope.
Not all eukaryotic cells have all of the organelles listed below, and occasionally, exceptional species of cells are missing organelles which might otherwise be considered universal to eukaryotic cells (such as mitochondria). There are also occasional exceptions to the number of membranes surrounding organelles, listed in the tables below (e.g. some which are listed as double-membraned are sometimes found with single or triple membranes). In addition to this, the amount of the individual organelles varies depending upon the function of the specific cell to which it is found (example, muscle cells have more smooth endoplasmic reticulum which helps in muscle contraction)
Organelles which have double-membranes and their own DNA are believed by many biologists of having originally come from incompletely consumed or invading prokaryotic cells, which were adopted as a part of the invaded cell through endosymbiosis. Originally, the word organelle referred to large lipid-encased formerly autonomous endosymbiont within cells. As other intracellular compartments were discovered, the meaning was generalized (in the United States, mainly) to include any lipid-encased intracellular component with a specialized biochemical function.
Other related structures:
- cytosol
- endomembrane system
- nucleosome
- microtubule
- cell membrane
# Prokaryotic Cells
Prokaryotes are not as structurally complex as eukaryotes, and were thought not to have any compartments enclosed by lipid membranes. All bacterias are prokaryotic cells. They do not have membrane-bound organelles. In the past they were often viewed as having little internal organization, but slowly details are emerging about prokaryotic internal structures. One contributing discovery was that at least some prokaryotes have microcompartments, which are compartments enclosed by proteins.[1] Even more striking is the description of prokaryotic organelles, such as magnetosomes,[2][3] as well as the nucleus-like organelles of the Planctomycetes that are surrounded by lipid membranes.[4] | https://www.wikidoc.org/index.php/Organellar | |
238b6aefb8e94418a0a57ec9bc14ebc0ed656f59 | wikidoc | Organotin | Organotin
# Overview
Organotin compounds or stannanes are chemical compounds based on tin with hydrocarbon substituents. Organotin chemistry is part of the wider field of organometallic chemistry . The first organotin compound was diethyltindiiodide, discovered by Edward Frankland in 1849. An organotin compound is commercially applied as a hydrochloric acid scavenger (or heat stabilizer) in polyvinyl chloride and as a biocide. Tributyltin oxide (or tributyltin for short) has been extensively used as a wood preservative. Tributyltin compounds are used as marine anti-biofouling agents. Concerns over toxicity of these compounds (some reports describe biological effects to marine life at a concentration of 1 nanogram per liter) have led to a world-wide ban by the International Maritime Organization. n-Butyltin trichloride is used in the production of tin oxide layers on glass bottles by chemical vapor deposition.
# Preparation of organotin compounds
- reaction of a grignard reagent with tin halides for example tin tetrachloride
- Wurtz reaction like coupling of alkyl sodium compounds with tin halides yields tetraorgano tin compounds
- by an exchange reaction of tin halides with organo aluminium compounds (AlR3)
- triorganotin halides are prepared in the Kocheshkov redistribution reaction
As an example the organic synthesis of tributyl-stannane :
A Grignard reagent is prepared from magnesium turnings and (Z)-2-bromo-5-phenyl-2-pentene in dry tetrahydrofuran and titrated with tributyltin chloride until the solution decolourises. The resulting solution is stirred at room temperature for 1 hour and the solvent is removed in a rotavapor. Diethyl ether is added and the ether extract is washed with brine and filtered and the ether evaporates in a rotavapor. The crude product is kugelrohr distilled to yield tributyl-stannane as a colourless oil.
# Reactions of organotin compounds
- Stille reaction
# Use and toxicity
- Tetraorganotins are very stable molecules with low toxicity and low biological activity. They are unusable as biocides, but they can be metabolized to toxic triorganotin compounds. They are used as starting materials for catalysts.
- Triorganotins are very toxic. Tri-n-alkyltins are phytotoxic and therefore cannot be used in agriculture. Depending on the organic groups, they can be powerful bactericides and fungicides. Tributyltins are used as industrial biocides, eg. as antifungal agents in textiles and paper, wood pulp and paper mill systems, breweries, and industrial cooling systems. Tributyltins are also used in marine anti-fouling paint. Triphenyltins are used as active components of antifungal paints and agricultural fungicides. Other triorganotins are used as miticides and acaricides.
- Diorganotins have no antifungal activity, low toxicity, and low antibacterial activity, except for diphenyltins. They are used in polymer manufacturing, as PVC heat stabilizers, catalysts, in the manufacturing of polyurethane and silicone curing.
- Monoorganotins have no biocidal activity and their toxicity to mammals is very low. Methyltin, butyltin, octyltin and monoestertins are used as PVC heat stabilizers.
# Important compounds
- Tetrabutyltin starting material for the di- and tributyl compounds
- Dialkyl- and monoalkyltin octylthiogylates used as heat stabilizers for polyvinyl chloride
- Tributyltin oxide, a colorless to pale yellow liquid used in wood preservation
- Triphenyltin acetate, an off-white crystalline solid, used as an insecticide and a fungicide
- Triphenyltin chloride, a white crystalline solid, used as a biocide and an intermediate in chemical synthesis
- Trimethyltin chloride also a biocide
- Triphenyltin hydroxide, an off-white powder, used as a fungicide and to sterilize insect
- Fenbutatin oxide, a very stable white crystalline solid, for control of mites
- Azocyclotin, a colorless crystalline solid, used as a long-acting acaricide for control of spider mites on plants
- Cyhexatin, a white crystalline solid, used as an acaricide and miticide
- Hexamethylditin used as an intermediate in chemical synthesis
- Tetraethyltin, boiling point 63–65° /12 mm is a catalyst
# Hypercoordinated stannanes
Unlike their carbon analogues, tin compounds can also be coordinated to five atoms instead of the regular four. These hypercoordinated compounds usually have electronegative substituents for stabilization. In 2007 a room-temperature stable (in argon) all-carbon pentaorganostannane was reported as the lithium salt with this structure:
In this distorted trigonal bipyramidal structure the carbon to tin bond lengths (2.26Å apical, 2.17Å equatorial) are larger than regular C-Sn bonds (2.14Å) reflecting its hypervalent nature. | Organotin
# Overview
Organotin compounds or stannanes are chemical compounds based on tin with hydrocarbon substituents. Organotin chemistry is part of the wider field of organometallic chemistry [1]. The first organotin compound was diethyltindiiodide, discovered by Edward Frankland in 1849. An organotin compound is commercially applied as a hydrochloric acid scavenger (or heat stabilizer) in polyvinyl chloride and as a biocide. Tributyltin oxide (or tributyltin for short) has been extensively used as a wood preservative. Tributyltin compounds are used as marine anti-biofouling agents. Concerns over toxicity of these compounds (some reports describe biological effects to marine life at a concentration of 1 nanogram per liter) have led to a world-wide ban by the International Maritime Organization. n-Butyltin trichloride is used in the production of tin oxide layers on glass bottles by chemical vapor deposition.
# Preparation of organotin compounds
- reaction of a grignard reagent with tin halides for example tin tetrachloride
- Wurtz reaction like coupling of alkyl sodium compounds with tin halides yields tetraorgano tin compounds
- by an exchange reaction of tin halides with organo aluminium compounds (AlR3)
- triorganotin halides are prepared in the Kocheshkov redistribution reaction
As an example the organic synthesis of tributyl-[(Z)-5-phenyl-2-penten-2-yl]stannane [2]:
A Grignard reagent is prepared from magnesium turnings and (Z)-2-bromo-5-phenyl-2-pentene in dry tetrahydrofuran and titrated with tributyltin chloride until the solution decolourises. The resulting solution is stirred at room temperature for 1 hour and the solvent is removed in a rotavapor. Diethyl ether is added and the ether extract is washed with brine and filtered and the ether evaporates in a rotavapor. The crude product is kugelrohr distilled to yield tributyl-[(Z)-5-phenyl-2-penten-2-yl]stannane as a colourless oil.
# Reactions of organotin compounds
- Stille reaction
# Use and toxicity
- Tetraorganotins are very stable molecules with low toxicity and low biological activity. They are unusable as biocides, but they can be metabolized to toxic triorganotin compounds. They are used as starting materials for catalysts.
- Triorganotins are very toxic. Tri-n-alkyltins are phytotoxic and therefore cannot be used in agriculture. Depending on the organic groups, they can be powerful bactericides and fungicides. Tributyltins are used as industrial biocides, eg. as antifungal agents in textiles and paper, wood pulp and paper mill systems, breweries, and industrial cooling systems. Tributyltins are also used in marine anti-fouling paint. Triphenyltins are used as active components of antifungal paints and agricultural fungicides. Other triorganotins are used as miticides and acaricides.
- Diorganotins have no antifungal activity, low toxicity, and low antibacterial activity, except for diphenyltins. They are used in polymer manufacturing, as PVC heat stabilizers, catalysts, in the manufacturing of polyurethane and silicone curing.
- Monoorganotins have no biocidal activity and their toxicity to mammals is very low. Methyltin, butyltin, octyltin and monoestertins are used as PVC heat stabilizers.
# Important compounds
- Tetrabutyltin starting material for the di- and tributyl compounds
- Dialkyl- and monoalkyltin octylthiogylates used as heat stabilizers for polyvinyl chloride
- Tributyltin oxide, a colorless to pale yellow liquid used in wood preservation
- Triphenyltin acetate, an off-white crystalline solid, used as an insecticide and a fungicide
- Triphenyltin chloride, a white crystalline solid, used as a biocide and an intermediate in chemical synthesis
- Trimethyltin chloride also a biocide
- Triphenyltin hydroxide, an off-white powder, used as a fungicide and to sterilize insect
- Fenbutatin oxide, a very stable white crystalline solid, for control of mites
- Azocyclotin, a colorless crystalline solid, used as a long-acting acaricide for control of spider mites on plants
- Cyhexatin, a white crystalline solid, used as an acaricide and miticide
- Hexamethylditin used as an intermediate in chemical synthesis
- Tetraethyltin, boiling point 63–65° /12 mm is a catalyst [3]
# Hypercoordinated stannanes
Unlike their carbon analogues, tin compounds can also be coordinated to five atoms instead of the regular four. These hypercoordinated compounds usually have electronegative substituents for stabilization. In 2007 a room-temperature stable (in argon) all-carbon pentaorganostannane was reported [4] as the lithium salt with this structure:
In this distorted trigonal bipyramidal structure the carbon to tin bond lengths (2.26Å apical, 2.17Å equatorial) are larger than regular C-Sn bonds (2.14Å) reflecting its hypervalent nature. | https://www.wikidoc.org/index.php/Organotin | |
21de95b4416de3f7d44590d5c536014700f102bd | wikidoc | Oripavine | Oripavine
Oripavine is an opiate and the major metabolite of thebaine. It is the prototypical molecule of a series of semi-synthetic opioids which includes buprenorphine. Although its analgesic potency is comparable tomorphine, it is not used clinically due to its severe toxicity and low therapeutic index.
# Pharmacological Properties
Oripavine possesses an analgesic potency comparable to morphine; however, it is not clinically useful due to severe toxicity and low therapeutic index. In both mice and rats, toxic doses caused tonic-clonic_seizures followed by death, similar to thebaine.
Oripavine has a potential for dependence which is significantly greater than that of thebaine but slightly less than that of morphine.
# Legal Status
Due to the relative ease of synthetic modification of oripavine to produce other narcotics (by either direct or indirect routes via thebaine), the World Health Organization's Expert Committee on Drug Dependence recommended in 2003 that oripavine be controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. On March 14 2007, the United Nations Commission on Narcotic Drugs formally decided to accept these recommendations, and placed oripavine in the Schedule I.
Until recently, oripavine was a Schedule II drug in the United States by default as a thebaine derivative, although it was not explicitly listed. However, as a member state under the 1961 Single Convention on Narcotic Drugs, the US was obligated to specifically control the substance under the Controlled Substances Act following its international control by the UN Commission on Narcotic Drugs. On September 24 2007, the Drug Enforcement Administration formally added oripavine to Schedule II. | Oripavine
Template:Chembox new
Oripavine is an opiate and the major metabolite of thebaine. It is the prototypical molecule of a series of semi-synthetic opioids which includes buprenorphine. Although its analgesic potency is comparable tomorphine, it is not used clinically due to its severe toxicity and low therapeutic index.
# Pharmacological Properties
Oripavine possesses an analgesic potency comparable to morphine; however, it is not clinically useful due to severe toxicity and low therapeutic index. In both mice and rats, toxic doses caused tonic-clonic_seizures followed by death, similar to thebaine.[1]
Oripavine has a potential for dependence which is significantly greater than that of thebaine but slightly less than that of morphine.[2]
# Legal Status
Due to the relative ease of synthetic modification of oripavine to produce other narcotics (by either direct or indirect routes via thebaine), the World Health Organization's Expert Committee on Drug Dependence recommended in 2003 that oripavine be controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs.[3] On March 14 2007, the United Nations Commission on Narcotic Drugs formally decided to accept these recommendations, and placed oripavine in the Schedule I.[4]
Until recently, oripavine was a Schedule II drug in the United States by default as a thebaine derivative, although it was not explicitly listed. However, as a member state under the 1961 Single Convention on Narcotic Drugs, the US was obligated to specifically control the substance under the Controlled Substances Act following its international control by the UN Commission on Narcotic Drugs. On September 24 2007, the Drug Enforcement Administration formally added oripavine to Schedule II.[5] | https://www.wikidoc.org/index.php/Oripavine | |
c58042d9c223b21fbee88a05d6e9e2295b946ee3 | wikidoc | Ornithine | Ornithine
Ornithine is an amino acid, whose structure is:
# Role in urea cycle
Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen.
Ornithine is not an amino acid coded for by DNA, and in that sense, is not involved in protein synthesis. However, in mammalian non-hepatic tissues, the main use of the urea cycle is in arginine biosynthesis, so as an intermediate in metabolic processes, ornithine is quite important.
# Lactamization
It is believed to not be a part of genetic code because polypeptides containing unprotected ornithines undergo spontaneous lactamization. This proved to be a problem when ornithine was artificially incorporated in 21st amino acid systems.
# Other reactions
Ornithine, via the action of ornithine decarboxylase (E.C. 4.1.1.17), is the starting point for the synthesis of polyamines such as putrescine.
In bacteria, such as E. coli, ornithine can be synthesized from L-glutamate. | Ornithine
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Ornithine is an amino acid, whose structure is:
# Role in urea cycle
Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen.
Ornithine is not an amino acid coded for by DNA, and in that sense, is not involved in protein synthesis. However, in mammalian non-hepatic tissues, the main use of the urea cycle is in arginine biosynthesis, so as an intermediate in metabolic processes, ornithine is quite important.
# Lactamization
It is believed to not be a part of genetic code because polypeptides containing unprotected ornithines undergo spontaneous lactamization. This proved to be a problem when ornithine was artificially incorporated in 21st amino acid systems.
# Other reactions
Ornithine, via the action of ornithine decarboxylase (E.C. 4.1.1.17), is the starting point for the synthesis of polyamines such as putrescine.
In bacteria, such as E. coli, ornithine can be synthesized from L-glutamate.[1] | https://www.wikidoc.org/index.php/Ornithine | |
f4888cc82a99377354574047e6e0705342bbb607 | wikidoc | Osteopath | Osteopath
An osteopath is a practitioner of the approach to healthcare named osteopathy (or osteopathic medicine), which emphasises the importance of the musculoskeletal system on general health.
Osteopaths are trained to use various healthcare interventions and technologies depending on the location of their training. In the U.S., osteopaths are trained at osteopathic medical schools. They are fully licensed physicians, with the same practice rights as physicians who carry an M. D. degree. Osteopathic physicians earn the degree of Diploma of Osteopathy or Doctor of Osteopathic Medicine (D.O.).
Osteopathic Manipulative Medicine (OMM) is a form of manual therapy that includes an array of physical treatments, and in particular joint manipulation. OMM is taught at all osteopathic medical schools in the U.S., usually as an elective speciality. However, the practice of OMM has decreased in recent years, apparently due to limits placed by managed care.
# Additional notes by country
Outside of the U.S., most osteopaths are not physicians, and therefore most use drug-free, non-medical interventions. As a result of the emphasis given to the importance of the musculoskeletal system on health during their training, and their lack of prescribing rights, European, and other non-medical osteopaths provide predominantly OMM to their patients.
## Canada
Osteopaths trained in Canada, while once generally recognized as medical doctors, are not recognized as such by the Royal College of Physicians and Surgeons of Canada. At present, there is no accredited College of Osteopaths recognized by the RCPS, and therefore no creditable doctorate can be granted in Canada. However, the Ontario College of Physicians and Surgeons (and others) does recognize Osteopaths trained at accredited medical colleges in the U.S. and grants medical doctor-equivalent status to such Osteopathic Doctors.
Training in Osteopathy is given in Canada by such schools as the Canadian College of Osteopathy, and is overseen by the Canadian Council of Osteopathic Examiners, an accrediting body recognized by the Alternative Medicine Examiners Council of Canada. This body, however, is not empowered to license "Doctors" in the Canadian regulatory system, and the Canadian Osteopathic Association continues to undertake efforts to become recognized by the Royal College of Physicians and Surgeons of Canada. Canadian osteopathic training is more oriented around holistic or naturopathic medicine and is more akin to European osteopathy than American, as osteopathy organizations in Canada did not go through the same transformations as did those in the U.S. as a result of the Flexner Report.
Chiropractors, in canada, can be primary care physicians, and often chiropractors will be paired with allopathic or naturopatic doctors as alternatives to traditional osteopathy. The practicality of this combination provides some practical regulatory inertia against the efforts of osteopaths to become accredited in Canada.
## United Kingdom
The Osteopaths Act 1993 gave professional status to osteopaths and set up the General Osteopathic Council (GOsC) to provide for the regulation of professional standards for osteopathy. GOsC established 'Recognised Qualification' (RQ) criteria for training establishments offering osteopathic programmes of study. Only those with RQ status (such as The College of Osteopaths)can then have their successful graduates placed on the Register of Osteopaths maintained by GOsC. | Osteopath
An osteopath is a practitioner of the approach to healthcare named osteopathy (or osteopathic medicine), which emphasises the importance of the musculoskeletal system on general health.
Osteopaths are trained to use various healthcare interventions and technologies depending on the location of their training. In the U.S., osteopaths are trained at osteopathic medical schools. They are fully licensed physicians, with the same practice rights as physicians who carry an M. D. degree. Osteopathic physicians earn the degree of Diploma of Osteopathy or Doctor of Osteopathic Medicine (D.O.).
Osteopathic Manipulative Medicine (OMM) is a form of manual therapy that includes an array of physical treatments, and in particular joint manipulation. OMM is taught at all osteopathic medical schools in the U.S., usually as an elective speciality. However, the practice of OMM has decreased in recent years, apparently due to limits placed by managed care.[citation needed]
# Additional notes by country
Outside of the U.S., most osteopaths are not physicians, and therefore most use drug-free, non-medical interventions. As a result of the emphasis given to the importance of the musculoskeletal system on health during their training, and their lack of prescribing rights, European, and other non-medical osteopaths provide predominantly OMM to their patients.
## Canada
Osteopaths trained in Canada, while once generally recognized as medical doctors, are not recognized as such by the Royal College of Physicians and Surgeons of Canada. At present, there is no accredited College of Osteopaths recognized by the RCPS, and therefore no creditable doctorate can be granted in Canada. However, the Ontario College of Physicians and Surgeons (and others) does recognize Osteopaths trained at accredited medical colleges in the U.S. and grants medical doctor-equivalent status to such Osteopathic Doctors. [1]
Training in Osteopathy is given in Canada by such schools as the Canadian College of Osteopathy[2], and is overseen by the Canadian Council of Osteopathic Examiners, an accrediting body recognized by the Alternative Medicine Examiners Council of Canada.[3] This body, however, is not empowered to license "Doctors" in the Canadian regulatory system, and the Canadian Osteopathic Association continues to undertake efforts to become recognized by the Royal College of Physicians and Surgeons of Canada.[4] Canadian osteopathic training is more oriented around holistic or naturopathic medicine and is more akin to European osteopathy than American, as osteopathy organizations in Canada did not go through the same transformations as did those in the U.S. as a result of the Flexner Report.
Chiropractors, in canada, can be primary care physicians, and often chiropractors will be paired with allopathic or naturopatic doctors as alternatives to traditional osteopathy. The practicality of this combination provides some practical regulatory inertia against the efforts of osteopaths to become accredited in Canada.
## United Kingdom
The Osteopaths Act 1993 gave professional status to osteopaths and set up the General Osteopathic Council (GOsC) to provide for the regulation of professional standards for osteopathy. GOsC established 'Recognised Qualification' (RQ) criteria for training establishments offering osteopathic programmes of study. Only those with RQ status (such as The College of Osteopaths)can then have their successful graduates placed on the Register of Osteopaths maintained by GOsC. | https://www.wikidoc.org/index.php/Osteopath | |
fc386d715c56a5d579769f71e434f0acaf468cf5 | wikidoc | Osteotome | Osteotome
# Overview
An osteotome is an instrument used for cutting or preparing bone.
1. Today osteotomes are used in dental implantation. With the osteotome technique, osteoplastic procedures have been developed with which the bone quality (compaction
-f local bone) and bone quantity (ridge extension in horizontal and vertical dimension)
are routinely improved and adequate primary stability of the implants can be ensured
with a high degree of predictability.
2. The instrument invented by Bernhard Heine, a German physician in Würzburg in 1830 was used as a bone saw, especially for opening the skull.It is a kind of chain saw moved by turning a winder. Heine's osteotome is not used in surgery any longer. | Osteotome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An osteotome is an instrument used for cutting or preparing bone.
1. Today osteotomes are used in dental implantation. With the osteotome technique, osteoplastic procedures have been developed with which the bone quality (compaction
of local bone) and bone quantity (ridge extension in horizontal and vertical dimension)
are routinely improved and adequate primary stability of the implants can be ensured
with a high degree of predictability.[1]
2. The instrument invented by Bernhard Heine, a German physician in Würzburg in 1830 was used as a bone saw, especially for opening the skull.It is a kind of chain saw moved by turning a winder. Heine's osteotome is not used in surgery any longer. | https://www.wikidoc.org/index.php/Osteotome | |
e073c590f0402f0a70fb30b298677d9ee449594d | wikidoc | Ovalbumin | Ovalbumin
# Overview
Ovalbumin is the main protein found in egg white, making up 60-65% of the total protein. It belongs to the serpin superfamily of proteins, although unlike the majority of serpins it is unable to inhibit any proteases.
The function of ovalbumin is unknown, although it is presumed to be a storage protein.
# Research
Ovalbumin is an important protein in several different areas of research, including:
- general studies of protein structure and properties (because it is available in large quantities).
- studies of serpin structure and function (the fact that ovalbumin does not inhibit proteases means that by comparing its structure with that of inhibitory serpins, the structural characteristics required for inhibition can be determined).
- proteomics (chicken egg ovalbumin is commonly used as a molecular weight marker for calibrating electrophoresis gels).
- immunology (commonly used to stimulate an allergic reaction in test subjects).
# Structure
The ovalbumin protein of chickens is made up of 385 amino acids, and its relative molecular mass is 45 kD. It is a glycoprotein with 4 sites of glycosylation.
It is secreted from the cell, despite lacking an N-terminal leader sequence.
# Medicinal characteristics
In cases where poisoning by heavy metals (such as Iron) is suspected, ovalbumin may be administered. Ovalbumin chelates to heavy metals and traps the metal ions within the sulfhydryl bonds of the protein. Chelating prevents the absorption of the metals into the gastrointestinal tract and prevents poisoning. | Ovalbumin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ovalbumin is the main protein found in egg white, making up 60-65% of the total protein.[1] It belongs to the serpin superfamily of proteins, although unlike the majority of serpins it is unable to inhibit any proteases.[2]
The function of ovalbumin is unknown, although it is presumed to be a storage protein.[3]
# Research
Ovalbumin is an important protein in several different areas of research, including:
- general studies of protein structure and properties (because it is available in large quantities).
- studies of serpin structure and function (the fact that ovalbumin does not inhibit proteases means that by comparing its structure with that of inhibitory serpins, the structural characteristics required for inhibition can be determined).
- proteomics (chicken egg ovalbumin is commonly used as a molecular weight marker for calibrating electrophoresis gels).
- immunology (commonly used to stimulate an allergic reaction in test subjects).
# Structure
The ovalbumin protein of chickens is made up of 385 amino acids, and its relative molecular mass is 45 kD.[4] It is a glycoprotein with 4 sites of glycosylation.[4]
It is secreted from the cell, despite lacking an N-terminal leader sequence.[5]
# Medicinal characteristics
In cases where poisoning by heavy metals (such as Iron) is suspected, ovalbumin may be administered.[6] Ovalbumin chelates to heavy metals and traps the metal ions within the sulfhydryl bonds of the protein. Chelating prevents the absorption of the metals into the gastrointestinal tract and prevents poisoning. | https://www.wikidoc.org/index.php/Ovalbumin | |
90130d48e17261540a3f3678747cbbca2361d80d | wikidoc | Oxacillin | Oxacillin
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Oxacillin is an antibiotic that is FDA approved for the treatment of infections caused by penicillinase producing staphylococci. Common adverse reactions include rash, diarrhea, nausea.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Oxacillin is indicated in the treatment of infections caused by penicillinase producing staphylococci which have demonstrated susceptibility to the drug.
- Cultures and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug.
- Oxacillin may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. Oxacillin should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus, therapy should not be continued with oxacillin.
- To reduce the development of drug-resistant bacteria and maintain the effectiveness of Oxacillin Injection, USP and other antibacterial drugs, Oxacillin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxacillin in adult patients.
### Non–Guideline-Supported Use
- Bacteremia associated with intravascular line, due to methicillin-susceptible Staphylococcus aureus.
- Bacterial meningitis, methicillin-susceptible Staphylococcus aureus.
- Complication of catheter; Prophylaxis - Infectious disease; Prophylaxis.
- Infection of bone - Infectious disorder.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Oxacillin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxacillin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxacillin in pediatric patients.
# Contraindications
- A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.
# Warnings
- Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin.
- The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated. Although anaphylaxis is more frequent following parenteral administration, it has occurred in patients receiving oral penicillins.
- When penicillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, the drug should be discontinued and the patient should receive supportive treatment, e.g., artificial maintenance of ventilation, pressor amines, antihistamines, and corticosteroids. Individuals with a history of penicillin hypersensitivity may also experience allergic reactions when treated with a cephalosporin.
- Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Oxacillin Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
- C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use.
- Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
- If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Oxacillin in the drug label.
## Postmarketing Experience
- The reported incidence of allergic reactions to penicillin ranges from 0.7 to 10 percent. Sensitization is usually the result of treatment but some individuals have had immediate reactions when first treated.
- In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk and vaccines.
- Two types of allergic reactions to penicillins are noted clinically, immediate and delayed.
- Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death. Such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy but have occurred in patients receiving oral therapy.
- Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, and fever. Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon. Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy.
- Manifestations of this type of reaction include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.
- Neurotoxic reactions similar to those observed with penicillin G may occur with large intravenous doses of oxacillin, especially with patients with renal insufficiency.
- Renal tubular damage and interstitial nephritis have been associated infrequently with the administration of oxacillin. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.
- Pseudomembranous colitis has been reported with the use of oxacillin. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.
- Hepatotoxicity, characterized by fever, nausea, and vomiting associated with abnormal liver function tests, mainly elevated SGOT levels, has been associated with the use of oxacillin.
# Drug Interactions
- Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.
- Oxacillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins.
- Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate or well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxacillin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Oxacillin during labor and delivery.
### Nursing Mothers
- Penicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman.
### Pediatric Use
- Because of incompletely developed renal function in pediatric patients, oxacillin may not be completely excreted, with abnormally high blood levels resulting.
- Frequent blood levels are advisable in this group with dosage adjustments when necessary. All pediatric patients treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects. Safety and effectiveness in pediatric patients have not been established.
- The potential for toxic effects in pediatric patients from chemicals that may leach from the single dose premixed intravenous preparation in plastic containers has not been evaluated.
### Geriatic Use
- Clinical studies of Oxacillin injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.
- Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
- Oxacillin Injection contains 92.4 mg (4.02 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 92.4 and 554 mg/day (4.02 and 24.1 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
### Gender
There is no FDA guidance on the use of Oxacillin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Oxacillin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Oxacillin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Oxacillin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Oxacillin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Oxacillin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral.
- Intravenous.
### Monitoring
- Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
- If any impairment of renal function is suspected or known to exist, a reduction in the total dosage should be considered and blood levels monitored to avoid possible neurotoxic reactions.
- AST (SGOT) and ALT (SGPT) values should be obtained periodically during therapy to monitor for possible liver function abnormalities.
- All pediatric patients treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects. Safety and effectiveness in pediatric patients have not been established.
# IV Compatibility
There is limited information regarding IV Compatibility of Oxacillin in the drug label.
# Overdosage
- The signs and symptoms of oxacillin overdosage are those described in the ADVERSE REACTIONS section. If signs or symptoms occur, discontinue use of the medication, treat symptomatically, and institute appropriate supportive measures.
# Pharmacology
## Mechanism of Action
- Penicillinase-resistant penicillins exert a bactericidal action against penicillin susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.
## Structure
- Oxacillin Injection, USP is a sterile injectable product containing oxacillin which is added as oxacillin sodium, a semisynthetic penicillin derived from the penicillin nucleus, 6-aminopenicillanic acid.
- The structural formula of oxacillin sodium is as follows:
- Oxacillin Injection, USP is a frozen, iso-osmotic, sterile, nonpyrogenic premixed 50 mL solution containing 1 g or 2 g of oxacillin added as oxacillin sodium. Dextrose, USP has been added to the above dosages to adjust osmolality (approximately 1.5 g and 300 mg as dextrose hydrous to the 1 g and 2 g dosages respectively).
- Sodium Citrate Hydrous, USP has been added as a buffer (approximately 150 mg and 300 mg to the 1 g and 2 g dosages, respectively). The pH has been adjusted with hydrochloric acid and may have been adjusted with sodium hydroxide. The pH is 6.5 (6.0 to 8.5). The solution is intended for intravenous use after thawing to room temperature.
- This GALAXY container (PL 2040) is fabricated from a specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Oxacillin in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Oxacillin in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Oxacillin in the drug label.
# Clinical Studies
There is limited information regarding Oxacillin Clinical Studies in the drug label.
# How Supplied
- Oxacillin Injection, USP is supplied as a premixed frozen iso-osmotic solution in 50 mL single dose GALAXY plastic containers as follows:
- 2G3538 NDC 0338-1013-41 1 gram oxacillin
- 2G3539 NDC 0338-1015-41 2 grams oxacillin
## Storage
- Store at or below -20°C/-4°F
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Oxacillin in the drug label.
# Precautions with Alcohol
- Alcohol-Oxacillin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- OXACILLIN®
# Look-Alike Drug Names
There is limited information regarding Oxacillin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Oxacillin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
# Disclaimer
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# Overview
Oxacillin is an antibiotic that is FDA approved for the treatment of infections caused by penicillinase producing staphylococci. Common adverse reactions include rash, diarrhea, nausea.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Oxacillin is indicated in the treatment of infections caused by penicillinase producing staphylococci which have demonstrated susceptibility to the drug.
- Cultures and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug.
- Oxacillin may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. Oxacillin should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus, therapy should not be continued with oxacillin.
- To reduce the development of drug-resistant bacteria and maintain the effectiveness of Oxacillin Injection, USP and other antibacterial drugs, Oxacillin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxacillin in adult patients.
### Non–Guideline-Supported Use
- Bacteremia associated with intravascular line, due to methicillin-susceptible Staphylococcus aureus.
- Bacterial meningitis, methicillin-susceptible Staphylococcus aureus.
- Complication of catheter; Prophylaxis - Infectious disease; Prophylaxis.
- Infection of bone - Infectious disorder.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Oxacillin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxacillin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxacillin in pediatric patients.
# Contraindications
- A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.
# Warnings
- Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin.
- The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated. Although anaphylaxis is more frequent following parenteral administration, it has occurred in patients receiving oral penicillins.
- When penicillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, the drug should be discontinued and the patient should receive supportive treatment, e.g., artificial maintenance of ventilation, pressor amines, antihistamines, and corticosteroids. Individuals with a history of penicillin hypersensitivity may also experience allergic reactions when treated with a cephalosporin.
- Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Oxacillin Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
- C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use.
- Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
- If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Oxacillin in the drug label.
## Postmarketing Experience
- The reported incidence of allergic reactions to penicillin ranges from 0.7 to 10 percent. Sensitization is usually the result of treatment but some individuals have had immediate reactions when first treated.
- In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk and vaccines.
- Two types of allergic reactions to penicillins are noted clinically, immediate and delayed.
- Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death. Such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy but have occurred in patients receiving oral therapy.
- Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, and fever. Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon. Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy.
- Manifestations of this type of reaction include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.
- Neurotoxic reactions similar to those observed with penicillin G may occur with large intravenous doses of oxacillin, especially with patients with renal insufficiency.
- Renal tubular damage and interstitial nephritis have been associated infrequently with the administration of oxacillin. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.
- Pseudomembranous colitis has been reported with the use of oxacillin. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.
- Hepatotoxicity, characterized by fever, nausea, and vomiting associated with abnormal liver function tests, mainly elevated SGOT levels, has been associated with the use of oxacillin.
# Drug Interactions
- Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.
- Oxacillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins.
- Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate or well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxacillin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Oxacillin during labor and delivery.
### Nursing Mothers
- Penicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman.
### Pediatric Use
- Because of incompletely developed renal function in pediatric patients, oxacillin may not be completely excreted, with abnormally high blood levels resulting.
- Frequent blood levels are advisable in this group with dosage adjustments when necessary. All pediatric patients treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects. Safety and effectiveness in pediatric patients have not been established.
- The potential for toxic effects in pediatric patients from chemicals that may leach from the single dose premixed intravenous preparation in plastic containers has not been evaluated.
### Geriatic Use
- Clinical studies of Oxacillin injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.
- Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
- Oxacillin Injection contains 92.4 mg (4.02 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 92.4 and 554 mg/day (4.02 and 24.1 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
### Gender
There is no FDA guidance on the use of Oxacillin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Oxacillin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Oxacillin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Oxacillin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Oxacillin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Oxacillin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral.
- Intravenous.
### Monitoring
- Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
- If any impairment of renal function is suspected or known to exist, a reduction in the total dosage should be considered and blood levels monitored to avoid possible neurotoxic reactions.
- AST (SGOT) and ALT (SGPT) values should be obtained periodically during therapy to monitor for possible liver function abnormalities.
- All pediatric patients treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects. Safety and effectiveness in pediatric patients have not been established.
# IV Compatibility
There is limited information regarding IV Compatibility of Oxacillin in the drug label.
# Overdosage
- The signs and symptoms of oxacillin overdosage are those described in the ADVERSE REACTIONS section. If signs or symptoms occur, discontinue use of the medication, treat symptomatically, and institute appropriate supportive measures.
# Pharmacology
## Mechanism of Action
- Penicillinase-resistant penicillins exert a bactericidal action against penicillin susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.
## Structure
- Oxacillin Injection, USP is a sterile injectable product containing oxacillin which is added as oxacillin sodium, a semisynthetic penicillin derived from the penicillin nucleus, 6-aminopenicillanic acid.
- The structural formula of oxacillin sodium is as follows:
- Oxacillin Injection, USP is a frozen, iso-osmotic, sterile, nonpyrogenic premixed 50 mL solution containing 1 g or 2 g of oxacillin added as oxacillin sodium. Dextrose, USP has been added to the above dosages to adjust osmolality (approximately 1.5 g and 300 mg as dextrose hydrous to the 1 g and 2 g dosages respectively).
- Sodium Citrate Hydrous, USP has been added as a buffer (approximately 150 mg and 300 mg to the 1 g and 2 g dosages, respectively). The pH has been adjusted with hydrochloric acid and may have been adjusted with sodium hydroxide. The pH is 6.5 (6.0 to 8.5). The solution is intended for intravenous use after thawing to room temperature.
- This GALAXY container (PL 2040) is fabricated from a specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Oxacillin in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Oxacillin in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Oxacillin in the drug label.
# Clinical Studies
There is limited information regarding Oxacillin Clinical Studies in the drug label.
# How Supplied
- Oxacillin Injection, USP is supplied as a premixed frozen iso-osmotic solution in 50 mL single dose GALAXY plastic containers as follows:
- 2G3538 NDC 0338-1013-41 1 gram oxacillin
- 2G3539 NDC 0338-1015-41 2 grams oxacillin
## Storage
- Store at or below -20°C/-4°F
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Oxacillin in the drug label.
# Precautions with Alcohol
- Alcohol-Oxacillin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- OXACILLIN®[1]
# Look-Alike Drug Names
There is limited information regarding Oxacillin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Oxacillin | |
6d47524e07b7fbbb58c2064bbb9dcfc69936ad40 | wikidoc | Oxygen-18 | Oxygen-18
Oxygen-18 (18O) is a natural, stable isotope of oxygen and one of the environmental isotopes.
18O is an important precursor for the production of fluorodeoxyglucose (FDG) used in positron emission tomography (PET). Generally, in the radiopharmaceutical industry, enriched water (H218O) is bombarded with hydrogen ions in either a cyclotron or linear accelerator creating fluorine-18. This is then synthesized into FDG and injected into a patient.
# Paleoclimatology
In Arctic and Antarctic ice cores, O-18 is used to retrieve the original temperatures of the precipitation during different years by analyzing the isotope ratio of the respective annual layers of ice. This happens due to the differing weights of water with the normal isotope of oxygen, and water with oxygen-18. In the 1950s, Harold Urey performed an experiment in which he mixed both normal water and water with oxygen-18 in a barrel, and then partially froze the barrel's contents. The water with oxygen-18 sunk to the bottom of the barrel and was first to freeze. | Oxygen-18
Template:Infobox isotope
Oxygen-18 (18O) is a natural, stable isotope of oxygen and one of the environmental isotopes.
18O is an important precursor for the production of fluorodeoxyglucose (FDG) used in positron emission tomography (PET). Generally, in the radiopharmaceutical industry, enriched water (H218O) is bombarded with hydrogen ions in either a cyclotron or linear accelerator creating fluorine-18. This is then synthesized into FDG and injected into a patient.
# Paleoclimatology
In Arctic and Antarctic ice cores, O-18 is used to retrieve the original temperatures of the precipitation during different years by analyzing the isotope ratio of the respective annual layers of ice. This happens due to the differing weights of water with the normal isotope of oxygen, and water with oxygen-18. In the 1950s, Harold Urey performed an experiment in which he mixed both normal water and water with oxygen-18 in a barrel, and then partially froze the barrel's contents. The water with oxygen-18 sunk to the bottom of the barrel and was first to freeze. | https://www.wikidoc.org/index.php/Oxygen-18 | |
4c1fadb46d19b990212c367158f4ae247bada4de | wikidoc | Oxygenate | Oxygenate
Oxygenated substances have been infused with oxygen. The term usually refers to oxygenated fuels. Oxygenates are usually employed as gasoline additives to reduce carbon monoxide that is created during the burning of the fuel. Some oxygenates such as MTBE have been found to have contaminated groundwater, mostly through leaks in underground gasoline storage tanks.
In 2004, California and New York banned MTBE, generally replacing it with ethanol. Several other states started switching soon afterward.
Oxygenates may be based on alcohols or ethers. The most common oxygenates in use are:
- Alcohols:
Methanol (MeOH)
Ethanol (EtOH)
Isopropyl alcohol (IPA)
n-butanol (BuOH)
Gasoline grade t-butanol (GTBA)
- Methanol (MeOH)
- Ethanol (EtOH)
- Isopropyl alcohol (IPA)
- n-butanol (BuOH)
- Gasoline grade t-butanol (GTBA)
- Ethers:
Methyl tert-butyl ether (MTBE)
Tertiary amyl methyl ether (TAME)
Tertiary hexyl methyl ether (THEME)
Ethyl tertiary butyl ether (ETBE)
Tertiary amyl ethyl ether (TAEE)
Diisopropyl ether (DIPE)
- Methyl tert-butyl ether (MTBE)
- Tertiary amyl methyl ether (TAME)
- Tertiary hexyl methyl ether (THEME)
- Ethyl tertiary butyl ether (ETBE)
- Tertiary amyl ethyl ether (TAEE)
- Diisopropyl ether (DIPE)
In the United States, preferential regulatory and tax treatment of ethanol (and methanol) automotive fuels introduces complexities beyond the energy balance inherent in and the engineering merits of the fuels themselves. North American automakers have in 2006 and 2007 enthusiastically promoted a blend of 85% ethanol and 15% gasoline, marketed as E85, and their flex-fuel vehicles, e.g. GM's "Live Green, Go Yellow" campaign. The apparent motivation for this is the nature of U.S. Corporate Average Fuel Economy (CAFE) standards, which give an effective 54% fuel efficiency bonus to vehicles capable of running on 85% alcohol blends over vehicles not adapted to run on 85% alcohol blends,. This regulatory artificiality is quite valuable to the North American auto manufacturers in avoiding fines for failing to meet CAFE fuel economy standards imposed upon each manufacturer's car and light truck fleets. In addition to this auto manufacturer-driven impetus for 85% alcohol blends, the United States Environmental Protection Agency had authority to mandate that minimum proportions of oxygenates be added to automotive gasoline on regional and seasonal bases from 1992 until 2006 in an attempt to reduce air pollution, in particular ground-level ozone and smog. As a consequence, much gasoline sold in the United States is blended with up to 10% of an unspecified oxygenating agent. This product is known formally as oxygenated fuel and often (but not entirely correctly, as there are Federally-mandated reformulated gasolines without oxygenate) as reformulated gasoline. Groundwater contamination scares and the State of California's ban of the substance as a gasoline additive has allowed ethanol to displace methyl tert(iary)-butyl ether (MTBE) as the most popular fuel oxygenate in the United States.
Many motorists in the U.S. did not welcome oxygenated gasoline because of its reduced energy density resulting in increased fuel consumption and because of fears of damage to cars, particularly to older cars. Alcohol (particularly methanol) fuel blends were expected to cause chemical damage to fuel system materials not designed to withstand exposure to alcohols, to increase water contamination due to alcohols' co-solvent properties, and via alcohols' solvent action loosening fixed fuel system deposits thus causing free-moving particulate contamination and clogging of various components. Experience with oxygenated fuels has shown little widespread deleterious mechanical effects, but oxygenated fuels have resulted in increased fuel consumption and often higher fuel prices. Although market conditions vary widely, ethanol is generally more expensive on a volumetric basis (and unquestionably more expensive on an energy content basis) than the gasoline with which it is blended. Refining and distribution complexities associated with regionally-specific oxygenated 'boutique gas' blends also has significantly raised gasoline prices in parts of the United States, particularly in California. Air pollution benefits from oxygenated fuels have thus far been difficult to quantify and to attribute to oxygenated fuel, but undoubtedly small.
Many American motorists see the promotion of, Federal subsidy for, and high import tariffs protecting domestic production of ethanol motor fuel and the Federal mandate for oxygenated gasoline to be essentially political phenomena. The principal driver in promoting E85 is the North American auto industry's need to avoid CAFE fines; in the fuel alcohol industry as a whole lobbying by American corn producers and agribusiness, in particular Archer Daniels Midland, the biggest ethanol producer in the United States, has done much to get the fuel alcohol industry its present subsidized and protected status. Advocates for wheat, corn and sugar growers have succeeded in their attempts to lobby for regulatory intervention encouraging adoption of ethanol, stimulating debate over who the major beneficiaries of increased use of ethanol would be. Some researchers have warned that ethanol produced from agricultural feedstocks will cause a global food shortage, contributing to starvation in the third world.
Most forms of automobile racing that require the use of gasoline as fuel (as opposed to higher-energy blended fuels or straight alcohols) prohibit the use of oxygenate compounds in fuels, as they can allow higher fuel burn than the engine intake restrictions are designed to permit. Prior to the 2007 Daytona 500, for example, NASCAR driver Michael Waltrip and his team were heavily penalized when evidence of an unspecified oxygenate compound was found in the car's intake manifold during inspections. | Oxygenate
Oxygenated substances have been infused with oxygen. The term usually refers to oxygenated fuels. Oxygenates are usually employed as gasoline additives to reduce carbon monoxide that is created during the burning of the fuel. Some oxygenates such as MTBE have been found to have contaminated groundwater, mostly through leaks in underground gasoline storage tanks.
In 2004, California and New York banned MTBE, generally replacing it with ethanol. Several other states started switching soon afterward.
Oxygenates may be based on alcohols or ethers. The most common oxygenates in use are:
- Alcohols:
Methanol (MeOH)
Ethanol (EtOH)
Isopropyl alcohol (IPA)
n-butanol (BuOH)
Gasoline grade t-butanol (GTBA)
- Methanol (MeOH)
- Ethanol (EtOH)
- Isopropyl alcohol (IPA)
- n-butanol (BuOH)
- Gasoline grade t-butanol (GTBA)
- Ethers:
Methyl tert-butyl ether (MTBE)
Tertiary amyl methyl ether (TAME)
Tertiary hexyl methyl ether (THEME)
Ethyl tertiary butyl ether (ETBE)
Tertiary amyl ethyl ether (TAEE)
Diisopropyl ether (DIPE)
- Methyl tert-butyl ether (MTBE)
- Tertiary amyl methyl ether (TAME)
- Tertiary hexyl methyl ether (THEME)
- Ethyl tertiary butyl ether (ETBE)
- Tertiary amyl ethyl ether (TAEE)
- Diisopropyl ether (DIPE)
In the United States, preferential regulatory and tax treatment of ethanol (and methanol) automotive fuels introduces complexities beyond the energy balance inherent in and the engineering merits of the fuels themselves. North American automakers have in 2006 and 2007 enthusiastically promoted a blend of 85% ethanol and 15% gasoline, marketed as E85, and their flex-fuel vehicles, e.g. GM's "Live Green, Go Yellow" campaign. The apparent motivation for this is the nature of U.S. Corporate Average Fuel Economy (CAFE) standards, which give an effective 54% fuel efficiency bonus to vehicles capable of running on 85% alcohol blends over vehicles not adapted to run on 85% alcohol blends,[1]. This regulatory artificiality is quite valuable to the North American auto manufacturers in avoiding fines for failing to meet CAFE fuel economy standards imposed upon each manufacturer's car and light truck fleets[2]. In addition to this auto manufacturer-driven impetus for 85% alcohol blends, the United States Environmental Protection Agency had authority to mandate that minimum proportions of oxygenates be added to automotive gasoline on regional and seasonal bases from 1992 until 2006 in an attempt to reduce air pollution, in particular ground-level ozone and smog. As a consequence, much gasoline sold in the United States is blended with up to 10% of an unspecified oxygenating agent. This product is known formally as oxygenated fuel and often (but not entirely correctly, as there are Federally-mandated reformulated gasolines without oxygenate) as reformulated gasoline. Groundwater contamination scares and the State of California's ban of the substance as a gasoline additive has allowed ethanol to displace methyl tert(iary)-butyl ether (MTBE) as the most popular fuel oxygenate in the United States.
Many motorists in the U.S. did not welcome oxygenated gasoline because of its reduced energy density resulting in increased fuel consumption and because of fears of damage to cars, particularly to older cars. Alcohol (particularly methanol) fuel blends were expected to cause chemical damage to fuel system materials not designed to withstand exposure to alcohols, to increase water contamination due to alcohols' co-solvent properties, and via alcohols' solvent action loosening fixed fuel system deposits thus causing free-moving particulate contamination and clogging of various components. Experience with oxygenated fuels has shown little widespread deleterious mechanical effects, but oxygenated fuels have resulted in increased fuel consumption and often higher fuel prices. Although market conditions vary widely, ethanol is generally more expensive on a volumetric basis (and unquestionably more expensive on an energy content basis) than the gasoline with which it is blended. Refining and distribution complexities associated with regionally-specific oxygenated 'boutique gas' blends also has significantly raised gasoline prices in parts of the United States, particularly in California. Air pollution benefits from oxygenated fuels have thus far been difficult to quantify and to attribute to oxygenated fuel, but undoubtedly small.
Many American motorists see the promotion of, Federal subsidy for, and high import tariffs protecting domestic production of ethanol motor fuel and the Federal mandate for oxygenated gasoline to be essentially political phenomena. The principal driver in promoting E85 is the North American auto industry's need to avoid CAFE fines; in the fuel alcohol industry as a whole lobbying by American corn producers and agribusiness, in particular Archer Daniels Midland, the biggest ethanol producer in the United States, has done much to get the fuel alcohol industry its present subsidized and protected status. Advocates for wheat, corn and sugar growers have succeeded in their attempts to lobby for regulatory intervention encouraging adoption of ethanol[3], stimulating debate over who the major beneficiaries of increased use of ethanol would be. Some researchers have warned that ethanol produced from agricultural feedstocks will cause a global food shortage[4], contributing to starvation in the third world.
Most forms of automobile racing that require the use of gasoline as fuel (as opposed to higher-energy blended fuels or straight alcohols) prohibit the use of oxygenate compounds in fuels, as they can allow higher fuel burn than the engine intake restrictions are designed to permit. Prior to the 2007 Daytona 500, for example, NASCAR driver Michael Waltrip and his team were heavily penalized when evidence of an unspecified oxygenate compound was found in the car's intake manifold during inspections. | https://www.wikidoc.org/index.php/Oxygenate | |
b84afe7d4da8f6a55d0a1f3dbfa19dd4bf87acc3 | wikidoc | PKC alpha | PKC alpha
Protein kinase C alpha (PKCα) is an enzyme that in humans is encoded by the PRKCA gene.
# Function
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca2+ handling in myocytes.
Protein kinase C-alpha (PKC-α) is a specific member of the protein kinase family. These enzymes are characterized by their ability to add a phosphate group to other proteins, thus changing their function. PKC-α has been widely studied in the tissues of many organisms including drosophila, xenopus, cow, dog, chicken, human, monkey, mouse, pig, and rabbit. Many studies are currently being conducted investigating the structure, function, and regulation of this enzyme. The most recent investigations concerning this enzyme include its general regulation, hepatic function, and cardiac function.
# Regulation
PKC-α is unique in its mode of regulation compared to other kinases within this family. In general, the protein kinase family is regulated by allosteric regulation, the binding of a modulating molecule that effects a conformational change in the enzyme and thus a change in the enzyme’s activity. The primary mode of PKC-α’s regulation, however, involves its interaction with the cell membrane, not direct interaction with specific molecules. The cell membrane consists of phospholipids. At warmer temperatures, phospholipids exist in a more fluid state as a result of increased intramolecular motion. The more fluid the cell membrane, the greater PKC-α’s activity. At cooler temperatures, phospholipids are found in a solid state with constricted motion. As phospholipids become stationary, they assume a particular orientation within the membrane. Phospholipids that solidify at an irregular or angled orientation with respect to the membrane, can reduce PKC-α’s activity.
The composition of the cell membrane can also affect PKC-α’s function. The presence of calcium ions, magnesium ions, and diacylglycerols (DAGs) are the most important because they influence the hydrophobic domain of the membrane. Varying concentrations of these three components constitute a longer or shorter length of the hydrophobic domain. Membranes with long hydrophobic domains result in decreased activity because it is harder for PKC-α to insert into the membrane. At low concentrations, the hydrophobic domain is shorter allowing PKC-α to readily insert into the membrane and its activity increases.
# Secondary structure
Using infrared spectroscopy techniques, researchers have demonstrated that the secondary structure of PKC alpha consists of around 44% beta sheets and nearly 22% alpha helices at 20°C. Upon addition of calcium ions, a slight increase in beta sheets to 48% was observed. Additional ligands normally associated with PKC alpha, such as PMA, ATP, and phospholipids had no effect on secondary structure.
The structure of PKC alpha was better preserved during denaturation of the enzyme at 75°C in the presence of calcium ions than in their absence. In one study, beta sheet composition only decreased by 13% with calcium ions present compared to 19% when absent.
# Role
## Epithelium
Another field of research has indicated that PKC-α plays a vital role in epithelial tissue, the tissue that covers all external and internal surfaces of the body. Specifically, PKC-α is involved in altering the function of tight junctions. Tight junctions exist at the meeting point between two cells. Here, tight junctions fuse together to form an impermeable barrier to not only large molecules such as proteins, but also smaller molecules like water. This prevents foreign molecules from entering the cell and helps regulate the internal environment of the cell. Cells infected with certain types of epithelial cancer exhibit increased PKC-α activity. This is a result of a change in the shape of the cell membrane, particularly in the areas where tight junctions exists. With greater activity of PKC-α, the tight junctions lose their ability to form a tight barrier. This causes an increased leakiness of the tight junctions and thus movement of molecules into the cells. In intestinal areas, luminal growth factors are able to enter the cell and increase the rate of cell growth. This is thought to be a promotional event that may prolong certain epithelial cancers.
## Liver
Much of the research of PKC alpha pertaining to its role in liver tissue involves the effects of bile acids on the phosphorylation mechanism of the PKC family of proteins. Past research has affirmed that the bile acid CDCA inhibits the healthy glucagon response through a phosphorylation-related sequence. In related studies further testing the effects of CDCA on hepatocytes, CDCA was shown to have induced PKC translocation to the plasma membrane. PKC alpha was favored in this process over PKC delta. The implications of this finding are that increased interaction between the glucagon receptor and PKC alpha could occur.
## Heart
PKC alpha is one of the lesser studied proteins of the PKC family because it is not highly regulated in the serious medical condition known as acute myocardial ischemia, which results from a lack of blood supply to the myocardium (heart muscle tissue). Recent research into the role of PKC alpha in cardiac tissue has indicated that it has an important role in stimulating hypertrophy. This was demonstrated by the ability of agonist-mediated hypertrophy to be stopped only as a result of the inhibition of PKC alpha in an experiment in situ. However, in further in vivo research using mice, the transgenic overexpression of PKC alpha showed no effect on cardiac growth, and the inhibition of PKC alpha showed no effect on hypertrophic response to increased cardiac pressure. On the contrary, research has shown that removing PKC alpha altogether improved the hearts ability to contract.
In summary, research is pointing in the direction that PKC alpha’s role in cardiac tissue has more impact as a regulator of contractility than of hypertrophy. In another study, the binding peptides, RACK and others derived from PKC beta, were expressed in mouse hearts. The genetic code for these proteins are similar to those of all isoforms of the PKC family (alpha, beta, and gamma). As such, RACK and other proteins can regulate the expression of all PKC family proteins. In this particular study, however, only PKC alpha was affected. Again, overexpression caused decreased contractile performance, whereas inhibition saw increased performance.
## Memory and PTSD
The scientists led by neuroscientist Dominique de Quervain of the University of Basel in Switzerland used memory tests and DNA studies to conclude that people who carried a particular DNA signature in at least one copy of a gene that encodes protein kinase C alpha had stronger memory than their peers; and brain scans of people with the genetic signature show stronger brain activation in parts of the prefrontal cortex compared with those who lacked the genetic feature. The team looked at the Rwandan refugees who had survived the 1994 genocide and found that the risk of PTSD in the refugees with strong memory signature is twice of that in the refugees without the genetic signature.
## Cell membrane
PKC-α shows important regulation of phospholipase D. Phospholipase D is located on the plasma membrane and is responsible for hydrolyzing phosphatidylcholine to phosphatidic acid and choline. Research has indicated that phospholipase D may play roles in tumorigenesis by altering cellular events such as invasion and migration. Point mutations at particular phenylalanine residues have shown to inhibit PKC-α’s ability to activate phospholipase D. Current research is being conducted investigating PKC-α’s inhibitory affects. Researchers hope to learn how to exploit PKC-α’s ability to turn down phospholipase D’s activity and use this function to create anti-cancer drugs.
Another breakthrough branch of research concerning PKC-α concerns its role in erythrocyte (red blood cell) development. Currently, researchers understand that PKC-α is correlated with the differentiation of erythroid progenitor cells in bone marrow. These undifferentiated cells give rise to the mass of red blood cells present in blood. Future research endeavors seek to find whether it is activation or inhibition of PKC-α which affects the development of erythrocytes. By answering this question, scientists hope to gain insight into various types of hematologic diseases such as aplastic anemia and leukemia.
# Pathology
Increased activation of PKCα is associated with the growth and invasion of cancers. High levels of PKCα are linked to malignant brain cancer. Moreover, a high proliferation rate of glioma tumor cells is the result of overexpression of isozyme PKCα.
# Interactions
PKC alpha has been shown to interact with:
- C1QBP,
- CD29,
- EGFR,
- FSCN1, and
- OGG1. | PKC alpha
Protein kinase C alpha (PKCα) is an enzyme that in humans is encoded by the PRKCA gene.
# Function
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca2+ handling in myocytes.[1]
Protein kinase C-alpha (PKC-α) is a specific member of the protein kinase family. These enzymes are characterized by their ability to add a phosphate group to other proteins, thus changing their function. PKC-α has been widely studied in the tissues of many organisms including drosophila, xenopus, cow, dog, chicken, human, monkey, mouse, pig, and rabbit. Many studies are currently being conducted investigating the structure, function, and regulation of this enzyme. The most recent investigations concerning this enzyme include its general regulation, hepatic function, and cardiac function.
# Regulation
PKC-α is unique in its mode of regulation compared to other kinases within this family. In general, the protein kinase family is regulated by allosteric regulation, the binding of a modulating molecule that effects a conformational change in the enzyme and thus a change in the enzyme’s activity. The primary mode of PKC-α’s regulation, however, involves its interaction with the cell membrane, not direct interaction with specific molecules.[2] The cell membrane consists of phospholipids. At warmer temperatures, phospholipids exist in a more fluid state as a result of increased intramolecular motion. The more fluid the cell membrane, the greater PKC-α’s activity. At cooler temperatures, phospholipids are found in a solid state with constricted motion. As phospholipids become stationary, they assume a particular orientation within the membrane. Phospholipids that solidify at an irregular or angled orientation with respect to the membrane, can reduce PKC-α’s activity.[2]
The composition of the cell membrane can also affect PKC-α’s function. The presence of calcium ions, magnesium ions, and diacylglycerols (DAGs) are the most important because they influence the hydrophobic domain of the membrane. Varying concentrations of these three components constitute a longer or shorter length of the hydrophobic domain. Membranes with long hydrophobic domains result in decreased activity because it is harder for PKC-α to insert into the membrane. At low concentrations, the hydrophobic domain is shorter allowing PKC-α to readily insert into the membrane and its activity increases.[2]
# Secondary structure
Using infrared spectroscopy techniques, researchers have demonstrated that the secondary structure of PKC alpha consists of around 44% beta sheets and nearly 22% alpha helices at 20°C.[3] Upon addition of calcium ions, a slight increase in beta sheets to 48% was observed. Additional ligands normally associated with PKC alpha, such as PMA, ATP, and phospholipids had no effect on secondary structure.[3]
The structure of PKC alpha was better preserved during denaturation of the enzyme at 75°C in the presence of calcium ions than in their absence. In one study, beta sheet composition only decreased by 13% with calcium ions present compared to 19% when absent.[3]
# Role
## Epithelium
Another field of research has indicated that PKC-α plays a vital role in epithelial tissue, the tissue that covers all external and internal surfaces of the body. Specifically, PKC-α is involved in altering the function of tight junctions. Tight junctions exist at the meeting point between two cells. Here, tight junctions fuse together to form an impermeable barrier to not only large molecules such as proteins, but also smaller molecules like water. This prevents foreign molecules from entering the cell and helps regulate the internal environment of the cell. Cells infected with certain types of epithelial cancer exhibit increased PKC-α activity. This is a result of a change in the shape of the cell membrane, particularly in the areas where tight junctions exists.[4] With greater activity of PKC-α, the tight junctions lose their ability to form a tight barrier.[5] This causes an increased leakiness of the tight junctions and thus movement of molecules into the cells. In intestinal areas, luminal growth factors are able to enter the cell and increase the rate of cell growth. This is thought to be a promotional event that may prolong certain epithelial cancers.
## Liver
Much of the research of PKC alpha pertaining to its role in liver tissue involves the effects of bile acids on the phosphorylation mechanism of the PKC family of proteins. Past research has affirmed that the bile acid CDCA inhibits the healthy glucagon response through a phosphorylation-related sequence. In related studies further testing the effects of CDCA on hepatocytes, CDCA was shown to have induced PKC translocation to the plasma membrane.[6] PKC alpha was favored in this process over PKC delta. The implications of this finding are that increased interaction between the glucagon receptor and PKC alpha could occur.[7]
## Heart
PKC alpha is one of the lesser studied proteins of the PKC family because it is not highly regulated in the serious medical condition known as acute myocardial ischemia, which results from a lack of blood supply to the myocardium (heart muscle tissue). Recent research into the role of PKC alpha in cardiac tissue has indicated that it has an important role in stimulating hypertrophy. This was demonstrated by the ability of agonist-mediated hypertrophy to be stopped only as a result of the inhibition of PKC alpha in an experiment in situ. However, in further in vivo research using mice, the transgenic overexpression of PKC alpha showed no effect on cardiac growth, and the inhibition of PKC alpha showed no effect on hypertrophic response to increased cardiac pressure. On the contrary, research has shown that removing PKC alpha altogether improved the hearts ability to contract.[8]
In summary, research is pointing in the direction that PKC alpha’s role in cardiac tissue has more impact as a regulator of contractility than of hypertrophy. In another study, the binding peptides, RACK and others derived from PKC beta, were expressed in mouse hearts. The genetic code for these proteins are similar to those of all isoforms of the PKC family (alpha, beta, and gamma). As such, RACK and other proteins can regulate the expression of all PKC family proteins. In this particular study, however, only PKC alpha was affected. Again, overexpression caused decreased contractile performance, whereas inhibition saw increased performance.[8]
## Memory and PTSD
The scientists led by neuroscientist Dominique de Quervain of the University of Basel in Switzerland used memory tests and DNA studies to conclude that people who carried a particular DNA signature in at least one copy of a gene that encodes protein kinase C alpha had stronger memory than their peers; and brain scans of people with the genetic signature show stronger brain activation in parts of the prefrontal cortex compared with those who lacked the genetic feature. The team looked at the Rwandan refugees who had survived the 1994 genocide and found that the risk of PTSD in the refugees with strong memory signature is twice of that in the refugees without the genetic signature.[9]
## Cell membrane
PKC-α shows important regulation of phospholipase D. Phospholipase D is located on the plasma membrane and is responsible for hydrolyzing phosphatidylcholine to phosphatidic acid and choline. Research has indicated that phospholipase D may play roles in tumorigenesis by altering cellular events such as invasion and migration. Point mutations at particular phenylalanine residues have shown to inhibit PKC-α’s ability to activate phospholipase D.[10] Current research is being conducted investigating PKC-α’s inhibitory affects. Researchers hope to learn how to exploit PKC-α’s ability to turn down phospholipase D’s activity and use this function to create anti-cancer drugs.
Another breakthrough branch of research concerning PKC-α concerns its role in erythrocyte (red blood cell) development. Currently, researchers understand that PKC-α is correlated with the differentiation of erythroid progenitor cells in bone marrow.[11] These undifferentiated cells give rise to the mass of red blood cells present in blood. Future research endeavors seek to find whether it is activation or inhibition of PKC-α which affects the development of erythrocytes.[11] By answering this question, scientists hope to gain insight into various types of hematologic diseases such as aplastic anemia and leukemia.
# Pathology
Increased activation of PKCα is associated with the growth and invasion of cancers.[12][13] High levels of PKCα are linked to malignant brain cancer.[14] Moreover, a high proliferation rate of glioma tumor cells is the result of overexpression of isozyme PKCα.[15]
# Interactions
PKC alpha has been shown to interact with:
- C1QBP,[16]
- CD29,[17][18]
- EGFR,[19]
- FSCN1,[20] and
- OGG1.[21] | https://www.wikidoc.org/index.php/PKC_alpha | |
eb21844eb1ca511159b3cd1e397f0376a945c7a7 | wikidoc | Trypsin 1 | Trypsin 1
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Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1 gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2 (anionic trypsinogen), and trypsin-3 (meso-trypsinogen).
# Function
This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7.
# Clinical significance
Its malfunction acts in an autosomal dominant manner to cause pancreatitis. Many mutations that can lead to pancreatitis have been found. An example is a mutation at Arg 117. Arg 117 is a trypsin-sensitive site which can be cleaved by another trypsin and becomes inactivated. This site may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated. Mutation at this cleavage site would result in a loss of control and permit autodigestion, causing pancreatitis. | Trypsin 1
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Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1 gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2 (anionic trypsinogen), and trypsin-3 (meso-trypsinogen).
# Function
This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7.[1]
# Clinical significance
Its malfunction acts in an autosomal dominant manner to cause pancreatitis. Many mutations that can lead to pancreatitis have been found.[2][3][4][5] An example is a mutation at Arg 117. Arg 117 is a trypsin-sensitive site which can be cleaved by another trypsin and becomes inactivated. This site may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated. Mutation at this cleavage site would result in a loss of control and permit autodigestion, causing pancreatitis.[6] | https://www.wikidoc.org/index.php/PRSS1 | |
1fe77139ffba48cc09a69868f060603675c806a1 | wikidoc | PX domain | PX domain
The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.
This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase). It was also identified in many other proteins involved in membrane trafficing, including nexins, Phospholipase D, and phosphoinositide-3-kinases.
The PX domain is structurally conserved in eukaryotes, although amino acid sequences show little similarity. PX domains interact primarily with PtdIns(3)P lipids. However some of them bind to Phosphatidic acid, (PtdIns(3,4)P2), PtdIns(3,5)P2, PtdIns(4,5)P2), and PtdIns(3,4,5)P3. The PX-domain can also interact with other domains and proteins. | PX domain
The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.
This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase). It was also identified in many other proteins involved in membrane trafficing, including nexins, Phospholipase D, and phosphoinositide-3-kinases.
The PX domain is structurally conserved in eukaryotes, although amino acid sequences show little similarity. PX domains interact primarily with PtdIns(3)P lipids. However some of them bind to Phosphatidic acid, (PtdIns(3,4)P2), PtdIns(3,5)P2, PtdIns(4,5)P2), and PtdIns(3,4,5)P3. The PX-domain can also interact with other domains and proteins.
# External links
- PX domain in Pfam
- UMich Orientation of Proteins in Membranes families/superfamily-60 - Calculated orientations of PX domains in membrane
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/PX_domain | |
68c34afef427b9b4c6de05224039b5b5834496a9 | wikidoc | Pack year | Pack year
A pack year is a quantification of cigarette smoking.
# Definition
A way to measure the amount a person has smoked over a long period of time. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, 1 pack year is equal to smoking 1 pack per day for 1 year, or 2 packs per day for half a year, and so on.
# Calculating 'Pack Years'
Number of pack years = (number of cigarettes smoked per day x number of years smoked)/20
For example: a patient who has smoked 15 cigarettes a day for 40 years has a (15x40)/20 = 30 pack year smoking history.
(1 pack has 20 cigarettes).
A pack-year is smoking 20 cigarettes a day for one year. If someone has smoked ten cigarettes a day for six years they
would have a three pack-year history. Someone who has smoked forty cigarettes daily for twenty years has a forty pack-year history.
# Significance and Usage
Quantification of pack years smoked is important in clinical care where degree of tobacco exposure is closely correlated to risk of disease. | Pack year
A pack year is a quantification of cigarette smoking.
# Definition
A way to measure the amount a person has smoked over a long period of time. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, 1 pack year is equal to smoking 1 pack per day for 1 year, or 2 packs per day for half a year, and so on.[1]
# Calculating 'Pack Years'
Number of pack years = (number of cigarettes smoked per day x number of years smoked)/20
For example: a patient who has smoked 15 cigarettes a day for 40 years has a (15x40)/20 = 30 pack year smoking history.
(1 pack has 20 cigarettes).
A pack-year is smoking 20 cigarettes a day for one year. If someone has smoked ten cigarettes a day for six years they
would have a three pack-year history. Someone who has smoked forty cigarettes daily for twenty years has a forty pack-year history.
# Significance and Usage
Quantification of pack years smoked is important in clinical care where degree of tobacco exposure is closely correlated to risk of disease. | https://www.wikidoc.org/index.php/Pack_year | |
fc0c0a3256a83327ff262029cd20f548237df33d | wikidoc | Page name | Page name
# Overview
The canonical form of a full page name is shown in large font as the page header. Another type of canonical form is what is in URLs generated by the system, for this page "Help:Page_name" with an underscore. Alternative names for this page (on most projects) are help:page name, help:Page name, Help:page name and Help:Page name, but not Help:Page Name; the alternative names for this page on this project are the bolded ones. For details, see below.
# Terms
The terms "full page name" and "full pagename" include the namespace prefix; the terms "page name" and "pagename" are somewhat ambiguous for pages outside the main namespace as they may or may not include the namespace prefix. To avoid ambiguity one can use "full pagename" and "pagename without namespace prefix".
# Restrictions
## Special characters
The following characters (the configuration is made in "$wgLegalTitleChars") are not allowed in page titles:
The non-printable characters with values 0 through 31, and the "delete" character 127, are also not allowed.
The reasons for disallowing these characters include:
- , {, }, and | have special meaning within Wikipedia's syntax, which are processed before the pagename is determined. For example, ] points at 2023, not a page called {{CURRENTYEAR}}.
In the default setup for MediaWiki, the + character is also not allowed in page titles. This can be added to $wgLegalTitleChars with
in LocalSettings.php
See also w:en:Wikipedia:Naming conventions (technical restrictions), and the {{DISPLAYTITLE}} magic word.
## Forward slash (/)
Depending on the namespace and the settings, a forward slash in the pagename provides special functionality: see subpage feature.
## Namespace prefixes
Also, the first part of a page name may not coincide with a project-independent namespace prefix that is automatically converted to another one. As an example, the name Project: A-Kon on Wikipedia is not possible.
The first part of a page name can coincide with a namespace prefix that is not converted. For example, there might be articles in the English Wikipedia about books called Wikipedia: The Big Adventure and Talk: Secrets are Bad (but only without the space after the colon). However, in that case the pages are in the wrong namespace. This may be inconvenient in searching or displaying a list of pages. Also, in the second case there is no link to a Talk page about the book. (As explained above, the second page name is not possible on e.g. the German Wikipedia: see w:de:Talk: Secrets are Bad).
--24.80.210.247 03:18, 5 March 2006 (UTC)--24.80.210.247 03:18, 5 March 2006 (UTC)
## Prefixes referring to other projects or pseudo-namespaces
A page name cannot start with a prefix that is in use to refer to another project, including language codes, e.g. "en:" (list), or one of the pseudo-namespaces "Media:" and "Special:".
Thus e.g. an article about the album "Q: Are We Not Men? A: We Are Devo!" can not have that exact name. An attempt to create the article, whether by a link Q: Are We Not Men? A: We Are Devo! or a URL :Are_We_Not_Men%3F_A:_We_Are_Devo%21 leads to Wikiquote.
With regard to using the prefix of the project itself there is no consistency: a name like en:a cannot be used on en: (try w:en:a and w:en:en:a), while "Q: Are We Not Men? A: We Are Devo!" can exist on Wikiquote: q:Q: Are We Not Men? A: We Are Devo!.
## Maximum page name length
The maximum page name length is 255 bytes (excluding the namespace prefix). Be aware that non-ASCII characters may take up to four bytes in UTF-8 encoding, so the total number of characters you can fit into a title may be less than 255 depending on the language it's in.
See
Test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test.
# Spaces vs. underscores
In page names, a blank space is equivalent with an underscore. A blank space is displayed in the large font title at the top of the page, the URLs show an underscore. See also below.
# Case-sensitivity
If for the first letter of a page name two cases exist, as in the case of letters of the Latin, Greek, Cyrillic, and Armenian alphabets, the following applies.
All characters of namespace prefixes are case-insensitive. The canonical form, shown in large font as page header, and in URLs generated by the system, is on most projects with one capital; Klingon is an exception, see w:tlh:Chen'ay':h:h, where the c is converted to lower-case, and w:tlh:Qah:Page name, where the h is converted to upper-case. Below "page name" refers to the name without the possible namespace prefix.
## Case-sensitivity of the first character
The first character of the page name (after the namespace prefix, if applicable) may or may not be case-sensitive, depending on the project (see mw:Manual:$wgCapitalLinks). ] gives on this project: Help:page name. If the first character of the page name is case-sensitive this is a link (to a different page), otherwise it is bold (a self link to this page).
On Wikimedia projects currently the first character of the page name is case-insensitive, except in all Wiktionaries.
Compare e.g. wikt:de:A and wikt:de:a.
### Case where the first character is case-insensitive
The canonical form is with a capital.
Note that in the case of a prefix that is not a namespace for the software, and in the case of a second prefix, the case-insensitivity does not apply to the first character after this prefix, e.g. Template:H:h Help and Template:H:H Help are distinguished.
## Case-sensitivity of the file name extension of an image
Note that even the file name extension of an image is case-sensitive: compare image:Stop_sign_us.jpg and image:Stop_sign_us.JPG
# Ignored spaces/underscores
Spaces/underscores which are ignored:
- those at the start and end of a full page name
- those at the end of a namespace prefix, before the colon
- those after the colon of the namespace prefix
- duplicate consecutive spaces
Some show up in the link label, e.g. ] becomes ___help__ :_ _template_ _, linking to Help:Template.
However, a space before or after a "normal" colon makes a difference, e.g. MediaWiki User's Guide: Editing overview and MediaWiki User's Guide : Editing overview, and MediaWiki User's Guide:Editing overview are all distinguished, because "MediaWiki User's Guide:" is a pseudo-namespace, not a real one.
# Coding of characters
A page name cannot contain e.g. %41, because that is automatically converted to the character A, for which %41 is the code. ] is rendered as A. Similarly %C3%80 is automatically converted to the character À. ] is rendered as À. The URL of the page is . One can argue what is the real name of the page, %C3%80 or À (a user will say the latter), but anyway there can not be distinct pages with these names.
# Canonical form
The inclusion tag for a non-existing page shows a link with the canonical form of the page name: {{qwsazx}}, {{:qwsazx}}, {{project:qws azx}} give Template:Qwsazx, Qwsazx, wikidoc:Qws azx; compare with ordinary links Template:qwsazx, qwsazx, project:qws azx; these work like Piped links, e.g. ]; in this case the conversion shows up on the referring page only when pointing at it: in the pop-up and in the status bar (if applicable for the browser); whether the target is a redirect, and what the final target is, is not shown at all.
An attempt to include a page from another project results in just displaying the wikitext, e.g. {{en:qwsazx}}; ordinary interwiki links do not show existence and do not show a canonical form in the hover box or status bar:. The same applies if interwiki link style is used for a link to a page in the same project: m:project:qwsazx.
A saved redirect page shows the canonical form of the target, even though the preview renders the link in the usual way, compare with the preview of .
Help:Alphabetic order
# Conversion of spaces to underscores etc.
There is no feature for just conversion of spaces to underscores and of special characters to escape codes, but there are two features for doing this in combination with something else: localurl (see Help:Variable) and PAGENAMEE.
Most needs for conversion are covered by these, but e.g. in a template one cannot link to a page with a given name {{{1}}} on a project with a different $wgScript.
## Variables PAGENAME and PAGENAMEE
The variable {{PAGENAME}} gives, for this page, Page name. {{PAGENAMEE}} gives Page_name.
Thus in the first case a space is used, in the second case an underscore, like in URLs. Similarly, À becomes the escape code %C3%80 (see above), and so on.
Example:
:Whatlinkshere&target={{NAMESPACE}}:{{PAGENAMEE}}
gives
:Whatlinkshere&target=:Page_name
Within localurl, {{PAGENAME}} should be used in the first part (because it is converted by localurl), or {{PAGENAMEE}} in the second part:
- {{fullurl:Special:Allpages|namespace=12&from={{PAGENAMEE}}}} gives here:
:Allpages&namespace=12&from=Page_name
- {{fullurl:Special:Allpages/{{PAGENAME}}|namespace=12}} gives here:
:Allpages/Page_name&namespace=12
Wrong:
- {{fullurl:Special:Allpages|namespace=12&from={{PAGENAME}}}} gives here:
:Allpages&namespace=12&from=Page name (wrong link)
- {{fullurl:Special:Allpages/{{PAGENAMEE}}|namespace=12}} gives here:
:Allpages/Page_name&namespace=12 (works here, the underscore, converted from a space, is not affected by the second conversion, but it does not work with special characters). | Page name
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The canonical form of a full page name is shown in large font as the page header. Another type of canonical form is what is in URLs generated by the system, for this page "Help:Page_name" with an underscore. Alternative names for this page (on most projects) are help:page name, help:Page name, Help:page name and Help:Page name, but not Help:Page Name; the alternative names for this page on this project are the bolded ones. For details, see below.
# Terms
The terms "full page name" and "full pagename" include the namespace prefix; the terms "page name" and "pagename" are somewhat ambiguous for pages outside the main namespace as they may or may not include the namespace prefix. To avoid ambiguity one can use "full pagename" and "pagename without namespace prefix".
# Restrictions
## Special characters
The following characters (the configuration is made in "$wgLegalTitleChars") are not allowed in page titles:
The non-printable characters with values 0 through 31, and the "delete" character 127, are also not allowed.
The reasons for disallowing these characters include:
- [, ], {, }, and | have special meaning within Wikipedia's syntax, which are processed before the pagename is determined. For example, [[{{CURRENTYEAR}}]] points at 2023, not a page called {{CURRENTYEAR}}.
In the default setup for MediaWiki, the + character is also not allowed in page titles. This can be added to $wgLegalTitleChars with
in LocalSettings.php
See also w:en:Wikipedia:Naming conventions (technical restrictions), and the {{DISPLAYTITLE}} magic word.
## Forward slash (/)
Depending on the namespace and the settings, a forward slash in the pagename provides special functionality: see subpage feature.
## Namespace prefixes
Also, the first part of a page name may not coincide with a project-independent namespace prefix that is automatically converted to another one. As an example, the name Project: A-Kon on Wikipedia is not possible.
The first part of a page name can coincide with a namespace prefix that is not converted. For example, there might be articles in the English Wikipedia about books called Wikipedia: The Big Adventure and Talk: Secrets are Bad (but only without the space after the colon). However, in that case the pages are in the wrong namespace. This may be inconvenient in searching or displaying a list of pages. Also, in the second case there is no link to a Talk page about the book. (As explained above, the second page name is not possible on e.g. the German Wikipedia: see w:de:Talk: Secrets are Bad).
--24.80.210.247 03:18, 5 March 2006 (UTC)--24.80.210.247 03:18, 5 March 2006 (UTC)
## Prefixes referring to other projects or pseudo-namespaces
A page name cannot start with a prefix that is in use to refer to another project, including language codes, e.g. "en:" (list), or one of the pseudo-namespaces "Media:" and "Special:".
Thus e.g. an article about the album "Q: Are We Not Men? A: We Are Devo!" can not have that exact name. An attempt to create the article, whether by a link Q: Are We Not Men? A: We Are Devo! or a URL http://en.wikipedia.org/wiki/Q:Are_We_Not_Men%3F_A:_We_Are_Devo%21 leads to Wikiquote.
With regard to using the prefix of the project itself there is no consistency: a name like en:a cannot be used on en: (try w:en:a and w:en:en:a), while "Q: Are We Not Men? A: We Are Devo!" can exist on Wikiquote: q:Q: Are We Not Men? A: We Are Devo!.
## Maximum page name length
The maximum page name length is 255 bytes (excluding the namespace prefix). Be aware that non-ASCII characters may take up to four bytes in UTF-8 encoding, so the total number of characters you can fit into a title may be less than 255 depending on the language it's in.
See
Test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test of maximum page name length: 255 characters; test.
# Spaces vs. underscores
In page names, a blank space is equivalent with an underscore. A blank space is displayed in the large font title at the top of the page, the URLs show an underscore. See also below.
# Case-sensitivity
If for the first letter of a page name two cases exist, as in the case of letters of the Latin, Greek, Cyrillic, and Armenian alphabets, the following applies.
All characters of namespace prefixes are case-insensitive. The canonical form, shown in large font as page header, and in URLs generated by the system, is on most projects with one capital; Klingon is an exception, see w:tlh:Chen'ay':h:h, where the c is converted to lower-case, and w:tlh:Qah:Page name, where the h is converted to upper-case. Below "page name" refers to the name without the possible namespace prefix.
## Case-sensitivity of the first character
The first character of the page name (after the namespace prefix, if applicable) may or may not be case-sensitive, depending on the project (see mw:Manual:$wgCapitalLinks). [[Help:page name]] gives on this project: Help:page name. If the first character of the page name is case-sensitive this is a link (to a different page), otherwise it is bold (a self link to this page).
On Wikimedia projects currently the first character of the page name is case-insensitive, except in all Wiktionaries.
Compare e.g. wikt:de:A and wikt:de:a.
### Case where the first character is case-insensitive
The canonical form is with a capital.
Note that in the case of a prefix that is not a namespace for the software, and in the case of a second prefix, the case-insensitivity does not apply to the first character after this prefix, e.g. Template:H:h Help and Template:H:H Help are distinguished.
## Case-sensitivity of the file name extension of an image
Note that even the file name extension of an image is case-sensitive: compare image:Stop_sign_us.jpg and image:Stop_sign_us.JPG
# Ignored spaces/underscores
Spaces/underscores which are ignored:
- those at the start and end of a full page name
- those at the end of a namespace prefix, before the colon
- those after the colon of the namespace prefix
- duplicate consecutive spaces
Some show up in the link label, e.g. [[___help__ :_ _template_ _]] becomes ___help__ :_ _template_ _, linking to Help:Template.
However, a space before or after a "normal" colon makes a difference, e.g. MediaWiki User's Guide: Editing overview and MediaWiki User's Guide : Editing overview, and MediaWiki User's Guide:Editing overview are all distinguished, because "MediaWiki User's Guide:" is a pseudo-namespace, not a real one.
# Coding of characters
A page name cannot contain e.g. %41, because that is automatically converted to the character A, for which %41 is the code. [[%41]] is rendered as A. Similarly %C3%80 is automatically converted to the character À. [[%C3%80]] is rendered as À. The URL of the page is http://meta.wikipedia.org/wiki/%C3%80. One can argue what is the real name of the page, %C3%80 or À (a user will say the latter), but anyway there can not be distinct pages with these names.
# Canonical form
The inclusion tag for a non-existing page shows a link with the canonical form of the page name: {{qwsazx}}, {{:qwsazx}}, {{project:qws azx}} give Template:Qwsazx, Qwsazx, wikidoc:Qws azx; compare with ordinary links Template:qwsazx, qwsazx, project:qws azx; these work like Piped links, e.g. [[Qwsazx|qwsazx]]; in this case the conversion shows up on the referring page only when pointing at it: in the pop-up and in the status bar (if applicable for the browser); whether the target is a redirect, and what the final target is, is not shown at all.
An attempt to include a page from another project results in just displaying the wikitext, e.g. {{en:qwsazx}}; ordinary interwiki links do not show existence and do not show a canonical form in the hover box or status bar:. The same applies if interwiki link style is used for a link to a page in the same project: m:project:qwsazx.
A saved redirect page shows the canonical form of the target, even though the preview renders the link in the usual way, compare [2] with the preview of [3].
Help:Alphabetic order
# Conversion of spaces to underscores etc.
There is no feature for just conversion of spaces to underscores and of special characters to escape codes, but there are two features for doing this in combination with something else: localurl (see Help:Variable) and PAGENAMEE.
Most needs for conversion are covered by these, but e.g. in a template one cannot link to a page with a given name {{{1}}} on a project with a different $wgScript.
## Variables PAGENAME and PAGENAMEE
The variable {{PAGENAME}} gives, for this page, Page name. {{PAGENAMEE}} gives Page_name.
Thus in the first case a space is used, in the second case an underscore, like in URLs. Similarly, À becomes the escape code %C3%80 (see above), and so on.
Example:
http://meta.wikimedia.org/w/wiki.phtml?title=Special:Whatlinkshere&target={{NAMESPACE}}:{{PAGENAMEE}}
gives
http://meta.wikimedia.org/w/wiki.phtml?title=Special:Whatlinkshere&target=:Page_name
Within localurl, {{PAGENAME}} should be used in the first part (because it is converted by localurl), or {{PAGENAMEE}} in the second part:
- {{fullurl:Special:Allpages|namespace=12&from={{PAGENAMEE}}}} gives here:
https://www.wikidoc.org/index.php?title=Special:Allpages&namespace=12&from=Page_name
- {{fullurl:Special:Allpages/{{PAGENAME}}|namespace=12}} gives here:
https://www.wikidoc.org/index.php?title=Special:Allpages/Page_name&namespace=12
Wrong:
- {{fullurl:Special:Allpages|namespace=12&from={{PAGENAME}}}} gives here:
https://www.wikidoc.org/index.php?title=Special:Allpages&namespace=12&from=Page name (wrong link)
- {{fullurl:Special:Allpages/{{PAGENAMEE}}|namespace=12}} gives here:
https://www.wikidoc.org/index.php?title=Special:Allpages/Page_name&namespace=12 (works here, the underscore, converted from a space, is not affected by the second conversion, but it does not work with special characters).
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Page_name | |
61390168057ee555b733a9ebda1ccdedba4cd403 | wikidoc | Paleozoic | Paleozoic
The Paleozoic or Palaeozoic Era (from the Greek palaio (παλαιο), "old" and zoe (ζωη), "life", meaning "ancient life") is the earliest of three geologic eras of the Phanerozoic eon. The Paleozoic spanned from roughly 542 to 251 million years ago (ICS, 2004), and is subdivided into six geologic periods; from oldest to youngest they are: the Cambrian, Ordovician, Silurian, Devonian, Carboniferous, and Permian.
# Paleozoic life
The Paleozoic covers the time from the first appearance of abundant, soft-shelled fossils to the time when the continents were beginning to be dominated by large, relatively sophisticated reptiles and modern plants. The lower (oldest) boundary was classically set at the first appearance of creatures known as trilobites and archeocyathids. The upper (youngest) boundary is set at a major extinction event 300 million years later, known as the Permian extinction. Modern practice sets the older boundary at the first appearance of a distinctive trace fossil called Trichophycus pedum.
At the start of the era, all life was confined to bacteria, algae, sponges and a variety of somewhat enigmatic forms known collectively as the Ediacaran fauna. A large number of body plans appeared nearly simultaneously at the start of the era -- a phenomenon known as the Cambrian Explosion. There is some evidence that simple life may already have invaded the land at the start of the Paleozoic, but substantial plants and animals did not take to the land until the Silurian and did not thrive until the Devonian. Although primitive vertebrates are known near the start of the Paleozoic, animal forms were dominated by invertebrates until the mid-Paleozoic. Fish populations exploded in the Devonian. During the late Paleozoic, great forests of primitive plants thrived on land forming the great coal beds of Europe and eastern North America. By the end of the era, the first large, sophisticated reptiles and the first modern plants (conifers) had developed.
# Tectonics
Geologically, the Paleozoic starts shortly after the breakup of a supercontinent called Pannotia and at the end of a global ice age. (See Varanger glaciation and Snowball Earth). Throughout the early Paleozoic, the Earth's landmass was broken up into a substantial number of relatively small continents. Toward the end of the era, the continents gathered together into a supercontinent called Pangaea, which included most of the Earth's land area.
# Climate
The Early Cambrian climate was probably moderate at first, becoming warmer over the course of the Cambrian, as the second-greatest sustained sea level rise in the Phanerozoic got underway. However, as if to offset this trend, Gondwana moved south with considerable speed, so that, in Ordovician time, most of West Gondwana (Africa and South America) lay directly over the South Pole. The Early Paleozoic climate was also strongly zonal, with the result that the "climate", in an abstract sense became warmer, but the living space of most organisms of the time -- the continental shelf marine environment -- became steadily colder. However, Baltica (Northern Europe and Russia) and Laurentia (eastern North America and Greenland) remained in the tropical zone, while China and Australia lay in waters which were at least temperate. The Early Paleozoic ended, rather abruptly, with the short, but apparently severe, Late Ordovician Ice Age. This cold spell caused the second-greatest mass extinction of Phanerozoic time. Over time, the warmer weather moved into the Paleozoic era.
The Middle Paleozoic was a time of considerable stability. Sea levels had dropped coincident with the Ice Age, but slowly recovered over the course of the Silurian and Devonian. The slow merger of Baltica and Laurentia, and the northward movement of bits and pieces of Gondwana created numerous new regions of relatively warm, shallow sea floor. As plants took hold on the continental margins, oxygen levels increased and carbon dioxide dropped, although much less dramatically. The north-south temperature gradient also seems to have moderated, or metazoan life simply became hardier, or both. At any event, the far southern continental margins of Antarctica and West Gondwana became increasingly less barren. The Devonian ended with a series of turnover pulses which killed off much of Middle Paleozoic vertebrate life, without noticeably reducing species diversity overall.
The Late Paleozoic was a time which has left us a good many unanswered questions. The Mississippian epoch began with a spike in atmospheric oxygen, while carbon dioxide plummeted to unheard-of lows. This destabilized the climate and led to one, and perhaps two, ice ages during the Carboniferous. These were far more severe than the brief Late Ordovician Ice; but, this time, the effects on world biota were inconsequential. By the Cisuralian, both oxygen and carbon dioxide had recovered to more normal levels. On the other hand, the assembly of Pangea created huge arid inland areas subject to temperature extremes. The Lopingian is associated with falling sea levels, increased carbon dioxide and general climatic deterioration, culminating in the devastation of the Permian extinction. | Paleozoic
The Paleozoic or Palaeozoic Era (from the Greek palaio (παλαιο), "old" and zoe (ζωη), "life", meaning "ancient life") is the earliest of three geologic eras of the Phanerozoic eon. The Paleozoic spanned from roughly 542 to 251 million years ago (ICS, 2004), and is subdivided into six geologic periods; from oldest to youngest they are: the Cambrian, Ordovician, Silurian, Devonian, Carboniferous, and Permian.
# Paleozoic life
The Paleozoic covers the time from the first appearance of abundant, soft-shelled fossils to the time when the continents were beginning to be dominated by large, relatively sophisticated reptiles and modern plants. The lower (oldest) boundary was classically set at the first appearance of creatures known as trilobites and archeocyathids. The upper (youngest) boundary is set at a major extinction event 300 million years later, known as the Permian extinction. Modern practice sets the older boundary at the first appearance of a distinctive trace fossil called Trichophycus pedum.
At the start of the era, all life was confined to bacteria, algae, sponges and a variety of somewhat enigmatic forms known collectively as the Ediacaran fauna. A large number of body plans appeared nearly simultaneously at the start of the era -- a phenomenon known as the Cambrian Explosion. There is some evidence that simple life may already have invaded the land at the start of the Paleozoic, but substantial plants and animals did not take to the land until the Silurian and did not thrive until the Devonian. Although primitive vertebrates are known near the start of the Paleozoic, animal forms were dominated by invertebrates until the mid-Paleozoic. Fish populations exploded in the Devonian. During the late Paleozoic, great forests of primitive plants thrived on land forming the great coal beds of Europe and eastern North America. By the end of the era, the first large, sophisticated reptiles and the first modern plants (conifers) had developed.
# Tectonics
Geologically, the Paleozoic starts shortly after the breakup of a supercontinent called Pannotia and at the end of a global ice age. (See Varanger glaciation and Snowball Earth). Throughout the early Paleozoic, the Earth's landmass was broken up into a substantial number of relatively small continents. Toward the end of the era, the continents gathered together into a supercontinent called Pangaea, which included most of the Earth's land area.
# Climate
The Early Cambrian climate was probably moderate at first, becoming warmer over the course of the Cambrian, as the second-greatest sustained sea level rise in the Phanerozoic got underway. However, as if to offset this trend, Gondwana moved south with considerable speed, so that, in Ordovician time, most of West Gondwana (Africa and South America) lay directly over the South Pole. The Early Paleozoic climate was also strongly zonal, with the result that the "climate", in an abstract sense became warmer, but the living space of most organisms of the time -- the continental shelf marine environment -- became steadily colder. However, Baltica (Northern Europe and Russia) and Laurentia (eastern North America and Greenland) remained in the tropical zone, while China and Australia lay in waters which were at least temperate. The Early Paleozoic ended, rather abruptly, with the short, but apparently severe, Late Ordovician Ice Age. This cold spell caused the second-greatest mass extinction of Phanerozoic time. Over time, the warmer weather moved into the Paleozoic era.
The Middle Paleozoic was a time of considerable stability. Sea levels had dropped coincident with the Ice Age, but slowly recovered over the course of the Silurian and Devonian. The slow merger of Baltica and Laurentia, and the northward movement of bits and pieces of Gondwana created numerous new regions of relatively warm, shallow sea floor. As plants took hold on the continental margins, oxygen levels increased and carbon dioxide dropped, although much less dramatically. The north-south temperature gradient also seems to have moderated, or metazoan life simply became hardier, or both. At any event, the far southern continental margins of Antarctica and West Gondwana became increasingly less barren. The Devonian ended with a series of turnover pulses which killed off much of Middle Paleozoic vertebrate life, without noticeably reducing species diversity overall.
The Late Paleozoic was a time which has left us a good many unanswered questions. The Mississippian epoch began with a spike in atmospheric oxygen, while carbon dioxide plummeted to unheard-of lows. This destabilized the climate and led to one, and perhaps two, ice ages during the Carboniferous. These were far more severe than the brief Late Ordovician Ice; but, this time, the effects on world biota were inconsequential. By the Cisuralian, both oxygen and carbon dioxide had recovered to more normal levels. On the other hand, the assembly of Pangea created huge arid inland areas subject to temperature extremes. The Lopingian is associated with falling sea levels, increased carbon dioxide and general climatic deterioration, culminating in the devastation of the Permian extinction. | https://www.wikidoc.org/index.php/Paleozoic | |
bc73daf19d446f46c0f79a6126dc6d23205ac75b | wikidoc | Palpation | Palpation
# Overview
Palpation is used as part of a physical examination in which an object is felt (usually with the hands of a healthcare practitioner) to determine its size, shape, firmness, or location. Palpation should not be confused with palpitation, which is an awareness of the beating of the heart.
# Uses
In the assessment of patients with pain conditions, practitioners (e.g. chiropractors, doctors of osteopathic medicine, physical therapists, and massage therapists) may use palpation to feel for tissue texture (e.g. swelling or muscle tone), to assess range and quality of joint motion, and to assess tenderness through tissue deformation (e.g. provoking pain with pressure or stretching). The scientific literature has shown that motion palpation is often unreliable between practitioners. In contrast, manual tests that provoke or relieve pain have been shown to be more reliable.
Palpation is typically employed for thoracic and abdominal examinations, but can also be used to diagnose edema and measure the pulse. It is used by veterinarians to check animals for pregnancy, and by midwives to determine the position of a fetus. | Palpation
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Palpation is used as part of a physical examination in which an object is felt (usually with the hands of a healthcare practitioner) to determine its size, shape, firmness, or location. Palpation should not be confused with palpitation, which is an awareness of the beating of the heart.
# Uses
In the assessment of patients with pain conditions, practitioners (e.g. chiropractors, doctors of osteopathic medicine, physical therapists, and massage therapists) may use palpation to feel for tissue texture (e.g. swelling or muscle tone), to assess range and quality of joint motion, and to assess tenderness through tissue deformation (e.g. provoking pain with pressure or stretching). The scientific literature has shown that motion palpation is often unreliable between practitioners. In contrast, manual tests that provoke or relieve pain have been shown to be more reliable.
Palpation is typically employed for thoracic and abdominal examinations, but can also be used to diagnose edema and measure the pulse. It is used by veterinarians to check animals for pregnancy, and by midwives to determine the position of a fetus. | https://www.wikidoc.org/index.php/Palpable | |
a11775d60d92e22b6a89a4df1f06c5fa7fdac23c | wikidoc | Palytoxin | Palytoxin
Palytoxin is an incredibly complex marine natural product containing 71 stereochemical elements. Palytoxin, isolated from soft coral, is considered to be one of the most toxic non-peptide substances known, second only to Maitotoxin. Palytoxin was originally isolated in 1971 in Hawaii from the seaweed-like coral, "Limu make o hana (Seaweed of Death from Hana)". Later, in 1982 its full chemical structure was published by Prof. Daisuke Uemura and coworkers at Nagoya University
. Professor Yoshito Kishi's group at Harvard University first synthesized palytoxin in 1994. This feat is still considered today by many to be the greatest synthetic accomplishment ever, due to its complexity in structure.
Palytoxin targets the sodium-potassium pump protein by binding to the molecule such that the molecule is locked in a position where it allows passive transport of both the sodium and potassium ions, thereby destroying the ion gradient that is essential for most cells.
Typical symptoms of palytoxin poisoning are angina-like chest pains, asthma-like breathing difficulties, tachycardia, unstable blood pressure, hemolysis (destruction of red blood cells), and an electrocardiogram showing an exaggerated T wave. The onset of symptoms is rapid, and death usually follows just minutes after.
Animal studies have shown that vasodilators, such as papverine and isosorbide nitrate, can be used as antidotes. The animal experiments only showed benefit if the antidotes were injected into the heart immediately following exposure. Treatment in humans is symptomatic and supportive.
# Footnotes
- ↑ Clayden, J., Greeves, N. (2000), pages 19-21
- ↑ Chemical Society of Japan, et al. (2005). "CSJ Award-2005 Prof. Daisuke Uemura" Retrieved on 24 July, 2007 from Chemical Soc. of Japan, Prof. D. Uemura
- ↑ Chemical Society of Japan, et al. (2005), -- "Its structural determination presented many difficulties. Dr. Uemura elucidated its planar structure in 1981 by repeatedly carrying out site-specific oxidative degradation and determined the structure of the degraded products using a sample that was originally isolated from Palythoa tuberculosa of Okinawa origin."
- ↑ Stereochemistry of Palytoxin. 4. Complete Structure, J. K. Cha, W. J. Christ, J. M. Finan, H. Fujioka, Y. Kishi, L. L. Klein, S. S. Ko, J. Leder, W. W. McWhorter, Jr., K. -P. Pfaff, M. Yonaga, D. Uemura, and Y. Hirata, J. Am. Chem. Soc., 104, 7369-7371 (1982)
- ↑ "Total Synthesis of Palytoxin Carboxylic Acid and Palytoxin Amide," R.W. Armstrong, J.-M. Beau, S.H. Cheon, W.J. Christ, H. Fujioka, W.-H. Ham, L.D. Hawkins, H. Jin, S.H. Kang, Y. Kishi, M.J. Martinelli, W.W. McWhorter, Jr., M. Mizuno, M. Nakata, A.E. Stutz, F.X. Talamas, M. Taniguchi, J.A. Tino, K. Ueda, J. Uenishi, J.B. White, and M. Yonaga, J. Am. Chem. Soc., 111, 7530 (1989)
- ↑ "Synthesis of Palytoxin from Palytoxin Carboxylic Acid", E.M. Suh and Y. Kishi, J. Am. Chem. Soc., 116, 11205 (1994).
- ↑ Wiles J, Vick J, Christensen M (1974). "Toxicological evaluation of palytoxin in several animal species". Toxicon. 12 (4): 427–33. PMID 4155146.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Palytoxin
Palytoxin is an incredibly complex marine natural product containing 71 stereochemical elements. Palytoxin, isolated from soft coral, is considered to be one of the most toxic non-peptide substances known, second only to Maitotoxin. Palytoxin was originally isolated in 1971 in Hawaii from the seaweed-like coral, "Limu make o hana (Seaweed of Death from Hana)"[1]. Later, in 1982 its full chemical structure was published by Prof. Daisuke Uemura and coworkers at Nagoya University [2]
[3]
[4]. Professor Yoshito Kishi's group at Harvard University first synthesized palytoxin in 1994[5][6]. This feat is still considered today by many to be the greatest synthetic accomplishment ever, due to its complexity in structure.
Palytoxin targets the sodium-potassium pump protein by binding to the molecule such that the molecule is locked in a position where it allows passive transport of both the sodium and potassium ions, thereby destroying the ion gradient that is essential for most cells.
Typical symptoms of palytoxin poisoning are angina-like chest pains, asthma-like breathing difficulties, tachycardia, unstable blood pressure, hemolysis (destruction of red blood cells), and an electrocardiogram showing an exaggerated T wave. The onset of symptoms is rapid, and death usually follows just minutes after.
Animal studies have shown that vasodilators, such as papverine and isosorbide nitrate, can be used as antidotes. The animal experiments only showed benefit if the antidotes were injected into the heart immediately following exposure.[7] Treatment in humans is symptomatic and supportive.
# Footnotes
- ↑ Clayden, J., Greeves, N. (2000), pages 19-21
- ↑ Chemical Society of Japan, et al. (2005). "CSJ Award-2005 Prof. Daisuke Uemura" Retrieved on 24 July, 2007 from http://www.chemistry.or.jp/csj-en/membership/awards/achieve/2005-uemura.html Chemical Soc. of Japan, Prof. D. Uemura
- ↑ Chemical Society of Japan, et al. (2005), -- "Its structural determination presented many difficulties. Dr. Uemura elucidated its planar structure in 1981 by repeatedly carrying out site-specific oxidative degradation and determined the structure of the degraded products using a sample that was originally isolated from Palythoa tuberculosa of Okinawa[n] origin."
- ↑ Stereochemistry of Palytoxin. 4. Complete Structure, J. K. Cha, W. J. Christ, J. M. Finan, H. Fujioka, Y. Kishi, L. L. Klein, S. S. Ko, J. Leder, W. W. McWhorter, Jr., K. -P. Pfaff, M. Yonaga, D. Uemura, and Y. Hirata, J. Am. Chem. Soc., 104, 7369-7371 (1982)
- ↑ "Total Synthesis of Palytoxin Carboxylic Acid and Palytoxin Amide," R.W. Armstrong, J.-M. Beau, S.H. Cheon, W.J. Christ, H. Fujioka, W.-H. Ham, L.D. Hawkins, H. Jin, S.H. Kang, Y. Kishi, M.J. Martinelli, W.W. McWhorter, Jr., M. Mizuno, M. Nakata, A.E. Stutz, F.X. Talamas, M. Taniguchi, J.A. Tino, K. Ueda, J. Uenishi, J.B. White, and M. Yonaga, J. Am. Chem. Soc., 111, 7530 (1989)
- ↑ "Synthesis of Palytoxin from Palytoxin Carboxylic Acid", E.M. Suh and Y. Kishi, J. Am. Chem. Soc., 116, 11205 (1994).
- ↑ Wiles J, Vick J, Christensen M (1974). "Toxicological evaluation of palytoxin in several animal species". Toxicon. 12 (4): 427–33. PMID 4155146.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Palytoxin | |
e6e636a089bf5b276e75fe37a05c22f6a67824ee | wikidoc | Pamaquine | Pamaquine
Pamaquine is an 8-aminoquinoline drug used for the treatment of malaria. It is closely related to primaquine.
# History
Pamaquine was the first synthetic antimalarial drug.
# Adverse effects
Like primaquine, pamaquine causes haemolytic anaemia in patients with G6PD deficiency. Patients should therefore always be screened for G6PD deficiency prior to being prescribed pamaquine.
# Uses
Pamaquine is effective against the hypnozoites of the relapsing malarias (P. vivax and P. ovale); and unlike primaquine, it is also very effective against the erythrocytic stages of all four human malarias. One small clinical trial of pamaquine as a causal prophylactic was disappointing (whereas primaquine is an extremely effective causal prophylactic).
# Dosing
60 mg once daily for 14–21 days.
When treating Plasmodium vivax, an initial course of chloroquine is unnecessary.
# Synonyms
- Plasmaquine | Pamaquine
Pamaquine is an 8-aminoquinoline drug used for the treatment of malaria. It is closely related to primaquine.
# History
Pamaquine was the first synthetic antimalarial drug.
# Adverse effects
Like primaquine, pamaquine causes haemolytic anaemia in patients with G6PD deficiency. Patients should therefore always be screened for G6PD deficiency prior to being prescribed pamaquine.
# Uses
Pamaquine is effective against the hypnozoites of the relapsing malarias (P. vivax and P. ovale); and unlike primaquine, it is also very effective against the erythrocytic stages of all four human malarias. One small clinical trial of pamaquine as a causal prophylactic was disappointing[1] (whereas primaquine is an extremely effective causal prophylactic).
# Dosing
60 mg once daily for 14–21 days.
When treating Plasmodium vivax, an initial course of chloroquine is unnecessary.
# Synonyms
- Plasmaquine | https://www.wikidoc.org/index.php/Pamaquine | |
a10f3371eb9bfcbeaea7a11149df286d68a0395a | wikidoc | Panaeolus | Panaeolus
Panaeolus is a genus of small, black-spored, saprotrophic agarics. The word Panaeolus is Greek for "all variegated", alluding to the spotted gills of the mushrooms produced.
# Characteristics
These fungi are mostly dung and grassland species, some of which are quite common in Europe and North America. The gills of Panaeolus do not deliquesce as do the members of the related genus Coprinus. Members of Panaeolus can also be mistaken for Psathyrella, however the later genus are usually found growing on wood.
The gills of these mushrooms are black or grey and have a spotty, speckled or cloudy appearance, caused by the way that the dark spores ripen together in tiny patches on the gill surface; different patches darken at different times. Another character of the genus is that the spores are smooth.
The closely related genus Panaeolina shares the spotted gills but they are dark brown (not black) and the spores are ornamented. This genus is sometimes treated as part of Panaeolus.
# Edibility
No members of Panaeolus are used for food, though some are used as a recreational drug. Thirteen species of Panaeolus contain the hallucinogen psilocybin including Panaeolus cyanescens and Panaeolus subbalteatus. The bluing hallucinogenic members of this genus are sometimes segregated into a separate genus, Copelandia.
Several members of this genus are known to contain psilocin and psilocybin and it is suspected that a number of other members of this genus contain unidentified psychoactive compounds. All members of this genus contain serotonin, urea, and tryptophan.
# Notable species
- Panaeolus acuminatus
- Panaeolus africanus
- Panaeolus bispora
- Panaeolus cambodginiensis
- Panaeolus castaneifolius
- Panaeolus cyanescens
- Panaeolus fimicola
- Panaeolus foenisecii (= Panaeolina foenisecii)
- Panaeolus papilionaceus var. papilionaceus
- Panaeolus papilionaceus var. parvisporus
- Panaeolus semiovatus var. phalaenarum (= Panaeolus antillarum)
- Panaeolus semiovatus var. semiovatus
- Panaeolus subbalteatus
- Panaeolus tropicalis | Panaeolus
Panaeolus is a genus of small, black-spored, saprotrophic agarics. The word Panaeolus is Greek for "all variegated", alluding to the spotted gills of the mushrooms produced.
# Characteristics
These fungi are mostly dung and grassland species, some of which are quite common in Europe and North America. The gills of Panaeolus do not deliquesce as do the members of the related genus Coprinus. Members of Panaeolus can also be mistaken for Psathyrella, however the later genus are usually found growing on wood.
The gills of these mushrooms are black or grey and have a spotty, speckled or cloudy appearance, caused by the way that the dark spores ripen together in tiny patches on the gill surface; different patches darken at different times. Another character of the genus is that the spores are smooth. [1]
The closely related genus Panaeolina shares the spotted gills but they are dark brown (not black) and the spores are ornamented. This genus is sometimes treated as part of Panaeolus. [2]
# Edibility
No members of Panaeolus are used for food, though some are used as a recreational drug. Thirteen [1] species of Panaeolus contain the hallucinogen psilocybin including Panaeolus cyanescens and Panaeolus subbalteatus. The bluing hallucinogenic members of this genus are sometimes segregated into a separate genus, Copelandia.
Several members of this genus are known to contain psilocin and psilocybin and it is suspected that a number of other members of this genus contain unidentified psychoactive compounds. [2] All members of this genus contain serotonin, urea, and tryptophan. [3]
# Notable species
- Panaeolus acuminatus
- Panaeolus africanus
- Panaeolus bispora
- Panaeolus cambodginiensis
- Panaeolus castaneifolius
- Panaeolus cyanescens
- Panaeolus fimicola
- Panaeolus foenisecii (= Panaeolina foenisecii)
- Panaeolus papilionaceus var. papilionaceus
- Panaeolus papilionaceus var. parvisporus
- Panaeolus semiovatus var. phalaenarum (= Panaeolus antillarum)
- Panaeolus semiovatus var. semiovatus
- Panaeolus subbalteatus
- Panaeolus tropicalis
# External links
- Key to Panaeolus in the Pacific Northwest
- Panaeolus - A Genus of Toadstools
- A Worldwide Geographical Distribution of the Neurotropic Fungi
- Wikispecies - Panaeolus | https://www.wikidoc.org/index.php/Panaeolus | |
da12953d2bc441de032f920aa4778e09f8b0ef40 | wikidoc | Panthenol | Panthenol
# Overview
Panthenol is the alcohol analog of pantothenic acid (vitamin B5), and is thus the provitamin of B5. In organisms it is quickly oxidized to pantothenate. Panthenol is a highly viscous transparent liquid at room temperature, but salts of pantothenic acid (for example sodium pantothenate) are powders (typically white). It is well soluble in water, alcohol and propylene glycol, soluble in ether and chloroform, and slightly soluble in glycerin.
Panthenol comes in two enantiomers, D and L. Only D-panthenol (dexpanthenol) is biologically active, however both forms have moisturizing properties. For cosmetic use, panthenol comes either in D form, or as a racemic mixture of D and L (DL-panthenol).
Pantothenol's expanded chemical formula is: HO-CH2-C(CH3)2-CH(OH)-CONH-CH2CH2CH2-OH.
# Uses
In cosmetics, panthenol is a humectant, emollient and moisturizer. It binds to hair follicles readily and is a frequent component of shampoos and hair conditioners (in concentrations of 0.1-1%). It coats the hair and seals its surface, lubricating follicles and making strands appear shiny.
In ointments it is mixed with allantoin, in concentrations of up to 2-5%, and is used for treatment of sunburns, mild burns and minor skin disorders.
Pantothenol is not, however, absorbed through the skin and thus has limited effects that are not due to its provitamin character.
If ingested, panthenol is metabolized to pantothenic acid.
Other names for panthenol are:
- Butanamide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, (R)-
- Butyramide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, D-(+)-
- Butanamide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, (2R)-
- D-Panthenol
- Dexpanthenol (DCIR)
- Dexpanthenolum
- Panthenol
- Propanolamine, N-pantoyl-
- d-Pantothenyl alcohol | Panthenol
Template:Chembox new
# Overview
Panthenol is the alcohol analog of pantothenic acid (vitamin B5), and is thus the provitamin of B5. In organisms it is quickly oxidized to pantothenate. Panthenol is a highly viscous transparent liquid at room temperature, but salts of pantothenic acid (for example sodium pantothenate) are powders (typically white). It is well soluble in water, alcohol and propylene glycol, soluble in ether and chloroform, and slightly soluble in glycerin.
Panthenol comes in two enantiomers, D and L. Only D-panthenol (dexpanthenol) is biologically active, however both forms have moisturizing properties. For cosmetic use, panthenol comes either in D form, or as a racemic mixture of D and L (DL-panthenol).
Pantothenol's expanded chemical formula is: HO-CH2-C(CH3)2-CH(OH)-CONH-CH2CH2CH2-OH.
# Uses
In cosmetics, panthenol is a humectant, emollient and moisturizer. It binds to hair follicles readily and is a frequent component of shampoos and hair conditioners (in concentrations of 0.1-1%). It coats the hair and seals its surface, lubricating follicles and making strands appear shiny.
In ointments it is mixed with allantoin, in concentrations of up to 2-5%, and is used for treatment of sunburns, mild burns and minor skin disorders.
Pantothenol is not, however, absorbed through the skin and thus has limited effects that are not due to its provitamin character.
If ingested, panthenol is metabolized to pantothenic acid.
Other names for panthenol are:
- Butanamide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, (R)-
- Butyramide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, D-(+)-
- Butanamide, 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-, (2R)-
- D-Panthenol
- Dexpanthenol (DCIR)
- Dexpanthenolum
- Panthenol
- Propanolamine, N-pantoyl-
- d-Pantothenyl alcohol
# External links
- PDR Online : Pantothenic Acid
- Sci-toys: ingredients: panthenol
- Household Products Database
Template:Preparations for treatment of wounds and ulcers
de:Dexpanthenol
hu:Dexpantenol
nl:Panthenol
sl:Pantenol
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Panthenol | |
5aa0bd7853d6d1a29355819ba47bcbed3541987c | wikidoc | Taste bud | Taste bud
# Overview
Taste buds are small structures on the upper surface of the tongue, soft palate, and epiglottis that provide information about the taste of food being eaten.
The human tongue has about 10,000 taste buds.
# Types of papillae
The majority of taste buds on the tongue sit on raised protrusions of the tongue surface called papillae. There are four types of papillae present in the human tongue:
- Fungiform papillae - as the name suggests, these are slightly mushroom shaped if looked at in section. These are present mostly at the apex (tip) of the tongue, as well as at the sides. Innervated by facial nerve.
- Filiform papillae - these are thin, long papillae "V"-shaped cones that don't contain taste buds but are the most numerous. These papillae are mechanical and not involved in gustation. Characterized increased keratinization.
- Foliate papillae - these are ridges and grooves towards the posterior part of the tongue found on lateral margins. Innervated by facial nerve (anterior papillae) and glossopharyngeal nerve (posterior papillae).
- Circumvallate papillae - there are only about 3-14 of these papillae on most people, and they are present at the back of the oral part of the tongue. They are arranged in a circular-shaped row just in front of the sulcus terminalis of the tongue. They are associated with ducts of Von Ebner's glands. Innervated by the glossopharyngeal nerve.
It is known that there are five taste sensations:
- Sweet, Bitter, and Umami (now sometimes called Savory), which work with a signal through a G-protein coupled receptor.
- Salty and Sour, which work with ion channels.
# Localization of taste and the human "tongue map"
Contrary to popular understanding that different tastes map to different areas of the tongue, taste qualities are found in all areas of the tongue.
The original "tongue map" was based on a mistranslation by Harvard psychologist Edwin G. Boring of a German paper that was written in 1901. Sensitivity to all tastes occurs across the whole tongue and indeed to other regions of the mouth where there are taste buds (epiglottis, soft palate).
# Structure of taste buds
Each taste bud is flask-like in shape, its broad base resting on the corium, and its neck opening by an orifice, the gustatory pore, between the cells of the epithelium.
The bud is formed by two kinds of cells: supporting cells and gustatory cells.
- The supporting (sustentacular) cells are mostly arranged like the staves of a cask, and form an outer envelope for the bud. Some, however, are found in the interior of the bud between the gustatory cells.
- The gustatory (taste) cells, a chemoreceptor, occupy the central portion of the bud; they are spindle-shaped, and each possesses a large spherical nucleus near the middle of the cell.
The peripheral end of the cell terminates at the gustatory pore in a fine hair-like filament, the gustatory hair.
The central process passes toward the deep extremity of the bud, and there ends in single or bifurcated varicosities.
The nerve fibrils after losing their medullary sheaths enter the taste bud, and end in fine extremities between the gustatory cells; other nerve fibrils ramify between the supporting cells and terminate in fine extremities; these, however, are believed to be nerves of ordinary sensation and not gustatory. | Taste bud
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Template:Infobox Anatomy
Taste buds are small structures on the upper surface of the tongue, soft palate, and epiglottis that provide information about the taste of food being eaten.
The human tongue has about 10,000 taste buds.
# Types of papillae
The majority of taste buds on the tongue sit on raised protrusions of the tongue surface called papillae. There are four types of papillae present in the human tongue:
- Fungiform papillae - as the name suggests, these are slightly mushroom shaped if looked at in section. These are present mostly at the apex (tip) of the tongue, as well as at the sides. Innervated by facial nerve.
- Filiform papillae - these are thin, long papillae "V"-shaped cones that don't contain taste buds but are the most numerous. These papillae are mechanical and not involved in gustation. Characterized increased keratinization.
- Foliate papillae - these are ridges and grooves towards the posterior part of the tongue found on lateral margins. Innervated by facial nerve (anterior papillae) and glossopharyngeal nerve (posterior papillae).
- Circumvallate papillae - there are only about 3-14 of these papillae on most people, and they are present at the back of the oral part of the tongue. They are arranged in a circular-shaped row just in front of the sulcus terminalis of the tongue. They are associated with ducts of Von Ebner's glands. Innervated by the glossopharyngeal nerve.
It is known that there are five taste sensations:
- Sweet, Bitter, and Umami (now sometimes called Savory), which work with a signal through a G-protein coupled receptor.
- Salty and Sour, which work with ion channels.
# Localization of taste and the human "tongue map"
Contrary to popular understanding that different tastes map to different areas of the tongue, taste qualities are found in all areas of the tongue.[1][2][3]
The original "tongue map" was based on a mistranslation by Harvard psychologist Edwin G. Boring of a German paper that was written in 1901.[4] Sensitivity to all tastes occurs across the whole tongue and indeed to other regions of the mouth where there are taste buds (epiglottis, soft palate).[5]
# Structure of taste buds
Each taste bud is flask-like in shape, its broad base resting on the corium, and its neck opening by an orifice, the gustatory pore, between the cells of the epithelium.
The bud is formed by two kinds of cells: supporting cells and gustatory cells.
- The supporting (sustentacular) cells are mostly arranged like the staves of a cask, and form an outer envelope for the bud. Some, however, are found in the interior of the bud between the gustatory cells.
- The gustatory (taste) cells, a chemoreceptor, occupy the central portion of the bud; they are spindle-shaped, and each possesses a large spherical nucleus near the middle of the cell.
The peripheral end of the cell terminates at the gustatory pore in a fine hair-like filament, the gustatory hair.
The central process passes toward the deep extremity of the bud, and there ends in single or bifurcated varicosities.
The nerve fibrils after losing their medullary sheaths enter the taste bud, and end in fine extremities between the gustatory cells; other nerve fibrils ramify between the supporting cells and terminate in fine extremities; these, however, are believed to be nerves of ordinary sensation and not gustatory. | https://www.wikidoc.org/index.php/Papillae_of_the_tongue | |
2964850794e730fa145ec2baa0824434379c9675 | wikidoc | Papilloma | Papilloma
# Overview
Papilloma refers to a benign epithelial tumor growing exophytically (outwardly projecting) in finger-like fronds. In this context Papilla refers to the projection created by the tumor, not a tumor on an already existing papilla (such as the nipple.)
# Causes
When used without context, it frequently refers to infections caused by Human papillomavirus. However, there are other conditions that cause papilloma, such as Choroid plexus papilloma (CPP).
Two types of papilloma often associated with HPV are "squamous cell papilloma" and "transitional cell papilloma" (also known as "bladder papilloma".)
# Symptoms
Papilloma in larynx may cayse hoarseness, cough and shortness of breath.
Symptoms of papilloma in breast may be bloody nipple discharge, pain and lump in breast.
Vulvar papilloma may cause itching, lump or ulcer even infection in vulva.
# Treatment
## Surgery
Surgery is recommended for the treatment of papilloma.
# Related Chapters
- Papilla
- Genital wart
- Laryngeal papillomatosis | Papilloma
For patient information click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Papilloma refers to a benign epithelial tumor growing exophytically (outwardly projecting) in finger-like fronds. In this context Papilla refers to the projection created by the tumor, not a tumor on an already existing papilla (such as the nipple.)
# Causes
When used without context, it frequently refers to infections caused by Human papillomavirus. However, there are other conditions that cause papilloma, such as Choroid plexus papilloma (CPP).
Two types of papilloma often associated with HPV are "squamous cell papilloma" and "transitional cell papilloma" (also known as "bladder papilloma".)
# Symptoms
Papilloma in larynx may cayse hoarseness, cough and shortness of breath.
Symptoms of papilloma in breast may be bloody nipple discharge, pain and lump in breast.
Vulvar papilloma may cause itching, lump or ulcer even infection in vulva.
# Treatment
## Surgery
Surgery is recommended for the treatment of papilloma.
# Related Chapters
- Papilla
- Genital wart
- Laryngeal papillomatosis
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Papilloma | |
3f74c40e3759437b2b6401deecdb800b55bda63b | wikidoc | Parahexyl | Parahexyl
Parahexyl (Synhexyl, n-hexyl-Δ3THC) is a synthetic analogue of THC, which was invented in 1949 during attempts to elucidate the structure of Δ9-THC, the active component of cannabis.
Parahexyl is similar in both structure and activity to THC, differing only in the position of one double bond, and the lengthening of the 3-pentyl chain by one CH2 group to n-hexyl. Parahexyl produces classic cannabis agonist effects in animals. It has a somewhat higher oral bioavailability than THC itself but is otherwise very similar. Presumably it acts as a CB1 agonist in the same way as THC but as there has been no research published using Parahexyl since the discovery of the CB1 receptor this has not been definitively confirmed.
Parahexyl was made illegal under UN convention in 1982 on the basis of its structural similarity and similar effects profile to THC, despite never having had any recorded instances of abuse by humans or illicit sale. Parahexyl was placed into the most restrictive Schedule 1 as a compound with no medical use, even though it has never been properly researched to see whether it might have medical use or not. | Parahexyl
Parahexyl (Synhexyl, n-hexyl-Δ3THC) is a synthetic analogue of THC, which was invented in 1949 during attempts to elucidate the structure of Δ9-THC, the active component of cannabis.
[1][2]
Parahexyl is similar in both structure and activity to THC, differing only in the position of one double bond, and the lengthening of the 3-pentyl chain by one CH2 group to n-hexyl. [3] Parahexyl produces classic cannabis agonist effects in animals. It has a somewhat higher oral bioavailability than THC itself but is otherwise very similar. [4] Presumably it acts as a CB1 agonist in the same way as THC but as there has been no research published using Parahexyl since the discovery of the CB1 receptor this has not been definitively confirmed.
Parahexyl was made illegal under UN convention in 1982 on the basis of its structural similarity and similar effects profile to THC, despite never having had any recorded instances of abuse by humans or illicit sale. Parahexyl was placed into the most restrictive Schedule 1 as a compound with no medical use, even though it has never been properly researched to see whether it might have medical use or not.
Template:Pharm-stub | https://www.wikidoc.org/index.php/Parahexyl | |
d01d90c5bcd548e7a64c5687ab30ca435e821f5e | wikidoc | Paramedic | Paramedic
A paramedic is a medical professional, usually a member of the emergency medical service, who responds to medical and trauma emergencies in the pre-hospital environment, provides emergency treatment and, when appropriate, transports a patient to definitive care, such as a hospital, for further assessment or follow-up care.
The use of the specific term paramedic varies by jurisdiction, and in some places is used to refer to any member of ambulance crew. In countries such as the United Kingdom, the use of the word paramedic is restricted by law, and the person claiming the title must have passed a specific set of examinations and clinical placements, and hold a valid registration with the governing body. Even in countries where the law restricts the title, popular media has created a culture where lay persons may refer to all emergency medical personnel as 'paramedics', even if they hold a lower qualification, such as emergency medical technician.
# Places of work
Paramedics are employed by a variety of different agencies: by government (as part of a public hospital system, as a separate municipal EMS service, or sometimes, especially in the United States, as part of a fire department) or by private sector organizations (private hospitals, private ambulance companies). Paramedics may also work in other settings (e.g., emergency departments, hospital inpatient units, medical clinics, doctors' offices, oil rigs, steel mills, Air Ambulances and casinos).
# Examples of skills performed by paramedics
Although there is a great deal of variation in what paramedics are trained and permitted to do from region to region, some skills performed by paramedics include:
- Basic Life Support/Advanced life support
- Advanced Cardiac Life Support - ACLS Such as:
Manual defibrillation;
Synchronized cardioversion;
Transcutaneous pacing;
Electrocardiogram monitoring and interpretation, including 12-lead ECG;
- Manual defibrillation;
- Synchronized cardioversion;
- Transcutaneous pacing;
- Electrocardiogram monitoring and interpretation, including 12-lead ECG;
- Pediatric care, such as Pediatric Advanced Life Support (PALS) or Pediatric Education for Prehospital Professionals (PEPP);
- Trauma care, such as Prehospital Trauma Life Support (PHTLS) or Basic or Advanced Trauma Life Support (BTLS or ATLS)
- Basic and advanced airway management, including:
Visualization the airway by use of the laryngoscope
removal of foreign bodies with Magill forceps;
Endotracheal and nasotracheal intubation, (including use of the Eschmann catheter);
Esophageal intubation using an EOA (now discontinued) or a CombiTube
Retrograde intubation;
Rapid Sequence Intubation (RSI);
Surgical cricothyroidotomy or needle cricothyrotomy/transtracheal jet insufflation;
Continuous positive airway pressure (CPAP)
- Visualization the airway by use of the laryngoscope
- removal of foreign bodies with Magill forceps;
- Endotracheal and nasotracheal intubation, (including use of the Eschmann catheter);
- Esophageal intubation using an EOA (now discontinued) or a CombiTube
- Retrograde intubation;
- Rapid Sequence Intubation (RSI);
- Surgical cricothyroidotomy or needle cricothyrotomy/transtracheal jet insufflation;
- Continuous positive airway pressure (CPAP)
- Vascular access for medication administration and fluid resuscitation via several routes:
Peripheral intravenous (IV) cannulation;
Intraosseous (IO) cannulation (placement of needle into marrow space of a large bone), by hand, with a drill or spring-loaded device;
- Peripheral intravenous (IV) cannulation;
- Intraosseous (IO) cannulation (placement of needle into marrow space of a large bone), by hand, with a drill or spring-loaded device;
- Pulse oximetry and capnography;
- Needle thoracotomy for tension pneumothorax;
- Glucometry (testing blood sugar) for diabetic patients
- Venous blood samples
- Ventilator and IV pump management
- Administration of medications via intramuscular, subcutaneous, intravenous, sublingual, endotracheal, rectal, oral, intranasal, intraosseous and buccal routes
Paramedics in some places administer a variety of emergency medications; the individual medications vary widely based on medical director preference, local standard of care, and law. These drugs range from calcium channel blockers that slow the heart rate to sympathomimetics like dopamine for severe hypotension (low blood pressure). Medications for treating respiratory conditions such as albuterol are common. They may also administer elective medications such as those which relieve pain or decrease nausea and vomiting. Nitroglycerin, aspirin, and morphine may be administered for chest pain. Other medications are used to treat cardiac conditions such as a myocardial infarction and various dysrhythmias.
In other places, the term paramedic is used to describe anyone who has a role in emergency medical care, and may not indicate a level of training or the ability to perform medical procedures at all.
# Different qualification levels across the world
In the US, there are 4 levels of prehospital care defined by the US Department of Transportation (which regulates prehospital education). In order of level of training, they are First Responder, Emergency Medical Technician-Basic (EMT-B), Emergency Medical Technician-Intermediate (EMT-I), and Emergency Medical Technician-Paramedic (EMT-P). Some systems within the US refer to both EMT-Ps and EMT-Is as "paramedics". In Canada there are 3 levels of Paramedics, with the Primary Care Paramedic equivalent to an EMT-B, the Advanced Care Paramedic equivalent to the standard paramedic, and the Critical Care Paramedic employed in the flight paramedic role (except in Alberta which uses the terms EMT and EMT-Paramedic).
In many parts of Europe and some cities in Canada, a different paradigm is used for prehospital care in which doctors, nurses and occasionally medical students function as prehospital providers, either in conjunction with or instead of paramedics. Other parts of the world, such as Hong Kong, are currently progressing toward a system staffed with paramedics. .
Paramedics may function under the authority and indirect supervision of a physician (as is the case in the United States), both through standing protocols (off-line medical control) or through direct physician consultation via phone or radio (on-line medical control), or, as is the case in the United Kingdom, they may be autonomous practitioners, with their own clincial judgement, ability to diagnose and prescribe.
# In the media
The 1970s television show Emergency! was a very popular series which centered on the work of paramedics in the Los Angeles County Fire Department, and the staff at the fictional Rampart Emergency Hospital. Emergency! has been widely credited with inspiring many municipalities to develop their own paramedic programs, and has inspired many to enter the fields of emergency medicine. The show was a top rated program for its entire production run (1972 - 1979), as well as in syndicated television reruns -- even inspiring a Saturday morning cartoon series.
Paramedics is also the name of a show on the Discovery Health Channel, which details the life and work of emergency medical squads across the country. It is also the name of a 1988 Comedy which highlighted the lighter side of EMS.
Paramedic: On the Front Lines of Medicine (1998), by Peter Canning, is an autobiographical account of a paramedic's first year on the job. Rescue 471: A Paramedic's Stories (2000) is the sequel.
Bringing Out the Dead (1999), directed by Martin Scorsese and starring Nicholas Cage is one of very few films about paramedics. The main character is paramedic Frank Pierce who works in New York's Hell's Kitchen. He's become burned out and haunted by visions of the people he's failed to save including a little girl.
Into the Breach: A Year of Life and Death with EMS (2002) Book written by J.A. Karam is the true story of paramedics, emergency medical technicians, and heavy-rescue specialists fighting to control trauma and medical emergencies. Into the Breach offers an unusual opportunity to bear witness to unimaginable suffering, heroic stoicism, and the inventiveness of American EMS workers fighting to save lives.
Parts of Third Watch (1999) were devoted to adventures of the fictional 55th precinct FDNY EMS unit, created by ER executive producer John Wells.
Saved (2006), a TNT series centered on paramedic Wyatt Cole (Tom Everett Scott), his partner, and their chaotic lives on and off the job. | Paramedic
A paramedic is a medical professional, usually a member of the emergency medical service, who responds to medical and trauma emergencies in the pre-hospital environment, provides emergency treatment and, when appropriate, transports a patient to definitive care, such as a hospital, for further assessment or follow-up care.
The use of the specific term paramedic varies by jurisdiction, and in some places is used to refer to any member of ambulance crew. In countries such as the United Kingdom, the use of the word paramedic is restricted by law, and the person claiming the title must have passed a specific set of examinations and clinical placements, and hold a valid registration with the governing body. Even in countries where the law restricts the title, popular media has created a culture where lay persons may refer to all emergency medical personnel as 'paramedics', even if they hold a lower qualification, such as emergency medical technician.[citation needed]
# Places of work
Paramedics are employed by a variety of different agencies: by government (as part of a public hospital system, as a separate municipal EMS service, or sometimes, especially in the United States, as part of a fire department) or by private sector organizations (private hospitals, private ambulance companies). Paramedics may also work in other settings (e.g., emergency departments, hospital inpatient units, medical clinics, doctors' offices, oil rigs, steel mills, Air Ambulances and casinos).
# Examples of skills performed by paramedics
Although there is a great deal of variation in what paramedics are trained and permitted to do from region to region, some skills performed by paramedics include:
- Basic Life Support/Advanced life support
- Advanced Cardiac Life Support - ACLS Such as:
Manual defibrillation;
Synchronized cardioversion;
Transcutaneous pacing;
Electrocardiogram monitoring and interpretation, including 12-lead ECG;
- Manual defibrillation;
- Synchronized cardioversion;
- Transcutaneous pacing;
- Electrocardiogram monitoring and interpretation, including 12-lead ECG;
- Pediatric care, such as Pediatric Advanced Life Support (PALS) or Pediatric Education for Prehospital Professionals (PEPP);
- Trauma care, such as Prehospital Trauma Life Support (PHTLS) or Basic or Advanced Trauma Life Support (BTLS or ATLS)
- Basic and advanced airway management, including:
Visualization the airway by use of the laryngoscope
removal of foreign bodies with Magill forceps;
Endotracheal and nasotracheal intubation, (including use of the Eschmann catheter);
Esophageal intubation using an EOA (now discontinued) or a CombiTube
Retrograde intubation;
Rapid Sequence Intubation (RSI);
Surgical cricothyroidotomy or needle cricothyrotomy/transtracheal jet insufflation;
Continuous positive airway pressure (CPAP)
- Visualization the airway by use of the laryngoscope
- removal of foreign bodies with Magill forceps;
- Endotracheal and nasotracheal intubation, (including use of the Eschmann catheter);
- Esophageal intubation using an EOA (now discontinued) or a CombiTube
- Retrograde intubation;
- Rapid Sequence Intubation (RSI);
- Surgical cricothyroidotomy or needle cricothyrotomy/transtracheal jet insufflation;
- Continuous positive airway pressure (CPAP)
- Vascular access for medication administration and fluid resuscitation via several routes:
Peripheral intravenous (IV) cannulation;
Intraosseous (IO) cannulation (placement of needle into marrow space of a large bone), by hand, with a drill or spring-loaded device;
- Peripheral intravenous (IV) cannulation;
- Intraosseous (IO) cannulation (placement of needle into marrow space of a large bone), by hand, with a drill or spring-loaded device;
- Pulse oximetry and capnography;
- Needle thoracotomy for tension pneumothorax;
- Glucometry (testing blood sugar) for diabetic patients
- Venous blood samples
- Ventilator and IV pump management
- Administration of medications via intramuscular, subcutaneous, intravenous, sublingual, endotracheal, rectal, oral, intranasal, intraosseous and buccal routes
Paramedics in some places administer a variety of emergency medications; the individual medications vary widely based on medical director preference, local standard of care, and law. These drugs range from calcium channel blockers that slow the heart rate to sympathomimetics like dopamine for severe hypotension (low blood pressure). Medications for treating respiratory conditions such as albuterol are common. They may also administer elective medications such as those which relieve pain or decrease nausea and vomiting. Nitroglycerin, aspirin, and morphine may be administered for chest pain. Other medications are used to treat cardiac conditions such as a myocardial infarction and various dysrhythmias.
In other places, the term paramedic is used to describe anyone who has a role in emergency medical care, and may not indicate a level of training or the ability to perform medical procedures at all.
# Different qualification levels across the world
In the US, there are 4 levels of prehospital care defined by the US Department of Transportation (which regulates prehospital education). In order of level of training, they are First Responder, Emergency Medical Technician-Basic (EMT-B), Emergency Medical Technician-Intermediate (EMT-I), and Emergency Medical Technician-Paramedic (EMT-P). Some systems within the US refer to both EMT-Ps and EMT-Is as "paramedics". In Canada there are 3 levels of Paramedics, with the Primary Care Paramedic equivalent to an EMT-B, the Advanced Care Paramedic equivalent to the standard paramedic, and the Critical Care Paramedic employed in the flight paramedic role (except in Alberta which uses the terms EMT and EMT-Paramedic).
In many parts of Europe and some cities in Canada, a different paradigm is used for prehospital care in which doctors, nurses and occasionally medical students function as prehospital providers, either in conjunction with or instead of paramedics. Other parts of the world, such as Hong Kong, are currently progressing toward a system staffed with paramedics. [1].
Paramedics may function under the authority and indirect supervision of a physician (as is the case in the United States), both through standing protocols (off-line medical control) or through direct physician consultation via phone or radio (on-line medical control), or, as is the case in the United Kingdom, they may be autonomous practitioners, with their own clincial judgement, ability to diagnose and prescribe.
# In the media
The 1970s television show Emergency! was a very popular series which centered on the work of paramedics in the Los Angeles County Fire Department, and the staff at the fictional Rampart Emergency Hospital. Emergency! has been widely credited with inspiring many municipalities to develop their own paramedic programs, and has inspired many to enter the fields of emergency medicine. The show was a top rated program for its entire production run (1972 - 1979), as well as in syndicated television reruns -- even inspiring a Saturday morning cartoon series.
Paramedics is also the name of a show on the Discovery Health Channel, which details the life and work of emergency medical squads across the country. It is also the name of a 1988 Comedy which highlighted the lighter side of EMS.
Paramedic: On the Front Lines of Medicine (1998), by Peter Canning, is an autobiographical account of a paramedic's first year on the job. Rescue 471: A Paramedic's Stories (2000) is the sequel.
Bringing Out the Dead (1999), directed by Martin Scorsese and starring Nicholas Cage is one of very few films about paramedics. The main character is paramedic Frank Pierce who works in New York's Hell's Kitchen. He's become burned out and haunted by visions of the people he's failed to save including a little girl.
Into the Breach: A Year of Life and Death with EMS (2002) Book written by J.A. Karam is the true story of paramedics, emergency medical technicians, and heavy-rescue specialists fighting to control trauma and medical emergencies. Into the Breach offers an unusual opportunity to bear witness to unimaginable suffering, heroic stoicism, and the inventiveness of American EMS workers fighting to save lives.
Parts of Third Watch (1999) were devoted to adventures of the fictional 55th precinct FDNY EMS unit, created by ER executive producer John Wells.
Saved (2006), a TNT series centered on paramedic Wyatt Cole (Tom Everett Scott), his partner, and their chaotic lives on and off the job. | https://www.wikidoc.org/index.php/Paramedic | |
cf607033baf3b3f36808ec355565ad29c9d2ab3f | wikidoc | Parecoxib | Parecoxib
# Overview
Parecoxib is a water soluble and injectable prodrug of valdecoxib. It is marketed as Dynastat in the European Union. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib (Celebrex) and rofecoxib (Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac (Toradol) is used in the United States. However, unlike ketorolac, parecoxib has no effect on platelet function and therefore does not promote bleeding during or after surgery. In addition, ketorolac has a much higher gastrointestinal toxicity profile compared to most other nonsteroidal antiinflammatory drugs (NSAIDs) including ibuprofen and naprosyn. However, in the United States ketorolac is the only injectable NSAID, although it is banned in many European countries due to concerns about surgical bleeding and stomach ulcers after surgery.
In 2005, the U.S. Food and Drug Administration (FDA) issued a letter of non-approval for parecoxib in the United States. No reasons were ever documented publicly for the non-approval, although one study noted increased occurrences of heart attacks following cardiac bypass surgery compared to placebo when high doses of parecoxib were used to control pain after surgery. It is also important to remember that rare but severe allergic reactions (Stevens-Johnson Syndrome, Lyell Syndrome) have been described with valdecoxib, the molecule to which parecoxib is converted. The drug is not approved for use after cardiac surgery in Europe. Ketorolac, still banned in much of Europe, and IV Ibuprofen are therefore the only options for IV NSAIDs in the United States, and it is not clear whether parecoxib will be resubmitted to the FDA in the future.
All anti-inflammatory medications in the U.S. carry the same warning regarding skin reactions, and none are approved for use during CABG surgery, so the reason for the FDA denying the approval of parecoxib remains unknown, but was likely related to political pressure from the US Congress to not approve another COX-2 selective inhibitor in the wake of the Vioxx affair. No COX-2 selective inhibitor has been approved in the US since that time, regardless of the safety profile of parecoxib in Europe. Efforts to find out the scientific rationale, or more likely the lack thereof, that the FDA used to justify the non-approval of parecoxib in the USA have proven futile due to secrecy issues. | Parecoxib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Parecoxib is a water soluble and injectable prodrug of valdecoxib. It is marketed as Dynastat in the European Union. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib (Celebrex) and rofecoxib (Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac (Toradol) is used in the United States. However, unlike ketorolac, parecoxib has no effect on platelet function and therefore does not promote bleeding during or after surgery. In addition, ketorolac has a much higher gastrointestinal toxicity profile compared to most other nonsteroidal antiinflammatory drugs (NSAIDs) including ibuprofen and naprosyn. However, in the United States ketorolac is the only injectable NSAID, although it is banned in many European countries due to concerns about surgical bleeding and stomach ulcers after surgery.
In 2005, the U.S. Food and Drug Administration (FDA) issued a letter of non-approval for parecoxib in the United States. No reasons were ever documented publicly for the non-approval, although one study noted increased occurrences of heart attacks following cardiac bypass surgery compared to placebo when high doses of parecoxib were used to control pain after surgery. It is also important to remember that rare but severe allergic reactions (Stevens-Johnson Syndrome, Lyell Syndrome) have been described with valdecoxib, the molecule to which parecoxib is converted.[1] The drug is not approved for use after cardiac surgery in Europe. Ketorolac, still banned in much of Europe, and IV Ibuprofen are therefore the only options for IV NSAIDs in the United States, and it is not clear whether parecoxib will be resubmitted to the FDA in the future.
All anti-inflammatory medications in the U.S. carry the same warning regarding skin reactions, and none are approved for use during CABG surgery, so the reason for the FDA denying the approval of parecoxib remains unknown, but was likely related to political pressure from the US Congress to not approve another COX-2 selective inhibitor in the wake of the Vioxx affair. No COX-2 selective inhibitor has been approved in the US since that time, regardless of the safety profile of parecoxib in Europe. Efforts to find out the scientific rationale, or more likely the lack thereof, that the FDA used to justify the non-approval of parecoxib in the USA have proven futile due to secrecy issues.[2] | https://www.wikidoc.org/index.php/Parecoxib | |
da1c2d897123b88fb202d78fef18a8e2bb100183 | wikidoc | Paregoric | Paregoric
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Paregoric is a antidiarrheal that is FDA approved for the treatment of diarrhea. Common adverse reactions include apnea, drug withdrawal, hypotension, respiratory depression, seizure, tachycardia.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Paregoric is useful for the treatment of diarrhea.
- 5 to 10 mL (1 to 2 teaspoonfuls) 1 to 4 times a day or as directed by a physician.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Paregoric in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Paregoric in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Paregoric is useful for the treatment of diarrhea.
- 0.25 to 0.5 mL/kg of body weight 1 to 4 times a day or as directed by a physician.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Paregoric in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Paregoric in pediatric patients.
# Contraindications
- Hypersensitivity to morphine. Because of its stimulating effect on the spinal cord, morphine should not be used in convulsive states, such as those occurring in status epilepticus, tetanus, and strychnine poisoning.
- This preparation should not be used in diarrhea caused by poisoning until the toxic material is eliminated from the gastrointestinal tract.
# Warnings
### Precautions
- Head Injury and Increased Intracranial Pressure
- The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce additional effects that may obscure the clinical course in patients with head injuries.
- Acute Abdominal Conditions
- The administration of morphine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
- Morphine should be given with caution to certain patients, such as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, and prostatic hypertrophy or urethral stricture.
- Morphine should be used with extreme caution in patients with disorders characterized by hypoxia, since even usual therapeutic doses of narcotics may decrease respiratory drive to the point of apnea while simultaneously increasing airway resistance.
- Hypotensive Effect
- The administration of morphine may result in severe hypotension in the postoperative patient or any individual whose ability to maintain blood pressure has been compromised by a depleted blood volume or the administration of such drugs as the phenothiazines or certain anesthetics.
- Supraventricular Tachycardias
- Because of a possible vagolytic action that may produce a significant increase in the ventricular response rate, morphine should be used with caution in patients with atrial flutter and other supraventricular tachycardias.
- Convulsions
- Morphine may aggravate preexisting convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels because of tolerance development, convulsions may occur in individuals without a history of convulsive disorders.
# Adverse Reactions
## Clinical Trials Experience
- The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.
- Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Paregoric in the drug label.
# Drug Interactions
- Morphine in combination with other narcotic analgesics, general anesthetics, phenothiazines, tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) has additive depressant effects, and the patient should be so advised. When such combination therapy is contemplated, the dosage of one or both agents should be reduced.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- Animal reproduction studies have not been conducted with morphine. It is not known whether morphine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Paregoric should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Paregoric in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Paregoric during labor and delivery.
### Nursing Mothers
- Morphine appears in the milk of nursing mothers. Caution should be exercised when paregoric is administered to a nursing woman.
### Pediatric Use
There is no FDA guidance on the use of Paregoric with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Paregoric with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Paregoric with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Paregoric with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Paregoric in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Paregoric in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Paregoric in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Paregoric in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Paregoric in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Paregoric in the drug label.
# Overdosage
- Paregoric is a Schedule III narcotic.
- Morphine can produce drug dependence and, therefore, has the potential for being abused. Patients receiving therapeutic dosage regimens of 10 mg every 4 hours for 1 to 2 weeks have exhibited mild withdrawal symptoms. Development of the dependent state is recognizable by an increased tolerance to the analgesic effect and the appearance of purposive phenomena (complaints, pleas, demands, or manipulative actions) shortly before the time of the next scheduled dose. A patient in withdrawal should be treated in a hospital environment. Usually, it is necessary only to provide supportive care with administration of a tranquilizer to suppress anxiety. Severe symptoms of withdrawal may require administration of a replacement narcotic.
- Serious overdosage of morphine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and, sometimes, bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.
- Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against the respiratory depression that may result from overdosage or unusual sensitivity to narcotics. Therefore, an appropriate dose of the antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of morphine may exceed that of the antagonist, the patient should be kept under continued surveillance, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.
- Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.
# Pharmacology
There is limited information regarding Paregoric Pharmacology in the drug label.
## Mechanism of Action
- Morphine produces its major effects on the central nervous system (CNS) and on the bowel.
## Structure
- Each 5 mL (teaspoonful) contains:
- Anhydrous Morphine . . . . . . . . . . . . . . . . . ……. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 mg (from opium tincture)
- Alcohol . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . not more than 47.0%
- Inactive Ingredients: anise oil, benzoic acid, camphor, alcohol, glycerin, and purified water.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Paregoric in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Paregoric in the drug label.
## Nonclinical Toxicology
- Paregoric has no known carcinogenic or mutagenic potential. However, no long-term animal studies are available to support this observation.
# Clinical Studies
There is limited information regarding Clinical Studies of Paregoric in the drug label.
# How Supplied
- Paregoric, USP contains anhydrous morphine 2 mg/5 mL (from opium tincture); alcohol not more than 47.0% and is available in 16 fl. oz. (473 mL) bottles.
tore at controlled room temperature, 15°-30°C (59°-86°F) .
- PROTECT FROM LIGHT
- AVOID EXCESSIVE HEAT
- Dispense in a tight, light-resistant container as defined in the USP. Use safety closures when dispensing this product unless otherwise directed by a physician or requested by the purchaser.
## Storage
There is limited information regarding Paregoric Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Information for Patients
- Morphine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery.
# Precautions with Alcohol
- Alcohol-Paregoric interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- OPIUM
# Look-Alike Drug Names
There is limited information regarding Paregoric Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Paregoric
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]
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# Overview
Paregoric is a antidiarrheal that is FDA approved for the treatment of diarrhea. Common adverse reactions include apnea, drug withdrawal, hypotension, respiratory depression, seizure, tachycardia.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Paregoric is useful for the treatment of diarrhea.
- 5 to 10 mL (1 to 2 teaspoonfuls) 1 to 4 times a day or as directed by a physician.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Paregoric in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Paregoric in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Paregoric is useful for the treatment of diarrhea.
- 0.25 to 0.5 mL/kg of body weight 1 to 4 times a day or as directed by a physician.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Paregoric in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Paregoric in pediatric patients.
# Contraindications
- Hypersensitivity to morphine. Because of its stimulating effect on the spinal cord, morphine should not be used in convulsive states, such as those occurring in status epilepticus, tetanus, and strychnine poisoning.
- This preparation should not be used in diarrhea caused by poisoning until the toxic material is eliminated from the gastrointestinal tract.
# Warnings
### Precautions
- Head Injury and Increased Intracranial Pressure
- The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce additional effects that may obscure the clinical course in patients with head injuries.
- Acute Abdominal Conditions
- The administration of morphine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
- Morphine should be given with caution to certain patients, such as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, and prostatic hypertrophy or urethral stricture.
- Morphine should be used with extreme caution in patients with disorders characterized by hypoxia, since even usual therapeutic doses of narcotics may decrease respiratory drive to the point of apnea while simultaneously increasing airway resistance.
- Hypotensive Effect
- The administration of morphine may result in severe hypotension in the postoperative patient or any individual whose ability to maintain blood pressure has been compromised by a depleted blood volume or the administration of such drugs as the phenothiazines or certain anesthetics.
- Supraventricular Tachycardias
- Because of a possible vagolytic action that may produce a significant increase in the ventricular response rate, morphine should be used with caution in patients with atrial flutter and other supraventricular tachycardias.
- Convulsions
- Morphine may aggravate preexisting convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels because of tolerance development, convulsions may occur in individuals without a history of convulsive disorders.
# Adverse Reactions
## Clinical Trials Experience
- The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.
- Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Paregoric in the drug label.
# Drug Interactions
- Morphine in combination with other narcotic analgesics, general anesthetics, phenothiazines, tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) has additive depressant effects, and the patient should be so advised. When such combination therapy is contemplated, the dosage of one or both agents should be reduced.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- Animal reproduction studies have not been conducted with morphine. It is not known whether morphine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Paregoric should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Paregoric in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Paregoric during labor and delivery.
### Nursing Mothers
- Morphine appears in the milk of nursing mothers. Caution should be exercised when paregoric is administered to a nursing woman.
### Pediatric Use
There is no FDA guidance on the use of Paregoric with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Paregoric with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Paregoric with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Paregoric with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Paregoric in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Paregoric in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Paregoric in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Paregoric in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Paregoric in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Paregoric in the drug label.
# Overdosage
- Paregoric is a Schedule III narcotic.
- Morphine can produce drug dependence and, therefore, has the potential for being abused. Patients receiving therapeutic dosage regimens of 10 mg every 4 hours for 1 to 2 weeks have exhibited mild withdrawal symptoms. Development of the dependent state is recognizable by an increased tolerance to the analgesic effect and the appearance of purposive phenomena (complaints, pleas, demands, or manipulative actions) shortly before the time of the next scheduled dose. A patient in withdrawal should be treated in a hospital environment. Usually, it is necessary only to provide supportive care with administration of a tranquilizer to suppress anxiety. Severe symptoms of withdrawal may require administration of a replacement narcotic.
- Serious overdosage of morphine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and, sometimes, bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.
- Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against the respiratory depression that may result from overdosage or unusual sensitivity to narcotics. Therefore, an appropriate dose of the antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of morphine may exceed that of the antagonist, the patient should be kept under continued surveillance, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.
- Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.
# Pharmacology
There is limited information regarding Paregoric Pharmacology in the drug label.
## Mechanism of Action
- Morphine produces its major effects on the central nervous system (CNS) and on the bowel.
## Structure
- Each 5 mL (teaspoonful) contains:
- Anhydrous Morphine . . . . . . . . . . . . . . . . . ……. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 mg (from opium tincture)
- Alcohol . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . not more than 47.0%
- Inactive Ingredients: anise oil, benzoic acid, camphor, alcohol, glycerin, and purified water.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Paregoric in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Paregoric in the drug label.
## Nonclinical Toxicology
- Paregoric has no known carcinogenic or mutagenic potential. However, no long-term animal studies are available to support this observation.
# Clinical Studies
There is limited information regarding Clinical Studies of Paregoric in the drug label.
# How Supplied
- Paregoric, USP contains anhydrous morphine 2 mg/5 mL (from opium tincture); alcohol not more than 47.0% and is available in 16 fl. oz. (473 mL) bottles.
tore at controlled room temperature, 15°-30°C (59°-86°F) [see USP].
- PROTECT FROM LIGHT
- AVOID EXCESSIVE HEAT
- Dispense in a tight, light-resistant container as defined in the USP. Use safety closures when dispensing this product unless otherwise directed by a physician or requested by the purchaser.
## Storage
There is limited information regarding Paregoric Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Information for Patients
- Morphine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery.
# Precautions with Alcohol
- Alcohol-Paregoric interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- OPIUM
# Look-Alike Drug Names
There is limited information regarding Paregoric Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Paregoric | |
2683b33325645c4a53da58fcb6e13195c5dd6e46 | wikidoc | Viscosity | Viscosity
Viscosity is a measure of the resistance of a fluid to being deformed by either shear stress or extensional stress. It is commonly perceived as "thickness", or resistance to flow. Viscosity describes a fluid's internal resistance to flow and may be thought of as a measure of fluid friction. Thus, water is "thin", having a lower viscosity, while vegetable oil is "thick" having a higher viscosity. All real fluids (except superfluids) have some resistance to stress, but a fluid which has no resistance to shear stress is known as an ideal fluid or inviscid fluid. The study of viscosity is known as rheology.
# Etymology
The word "viscosity" derives from the Latin word "viscum" for mistletoe. A viscous glue was made from mistletoe berries and used for lime-twigs to catch birds.
# Viscosity coefficients
When looking at a value for viscosity, the number that one most often sees is the coefficient of viscosity. There are several different viscosity coefficients depending on the nature of applied stress and nature of the fluid. They are introduced in the main books on hydrodynamics and rheology.
- Dynamic viscosity determines the dynamics of an incompressible Newtonian fluid;
- Kinematic viscosity is the dynamic viscosity divided by the density for a Newtonian fluid;
- Volume viscosity determines the dynamics of a compressible Newtonian fluid;
- Bulk viscosity is the same as volume viscosity
- Shear viscosity is the viscosity coefficient when the applied stress is a shear stress (valid for non-Newtonian fluids);
- Extensional viscosity is the viscosity coefficient when the applied stress is an extensional stress (valid for non-Newtonian fluids).
Shear viscosity and dynamic viscosity are much better known than the others. That is why they are often referred to as simply viscosity.
Simply put, this quantity is the ratio between the pressure exerted on the surface of a fluid, in the lateral or horizontal direction, to the change in velocity of the fluid as you move down in the fluid (this is what is referred to as a velocity gradient). For example, at "room temperature", water has a nominal viscosity of 1.0 × 10-3 Pa∙s and motor oil has a nominal apparent viscosity of 250 × 10-3 Pa∙s.
# Newton's theory
In general, in any flow, layers move at different velocities and the fluid's viscosity arises from the shear stress between the layers that ultimately opposes any applied force.
Isaac Newton postulated that, for straight, parallel and uniform flow, the shear stress, τ, between layers is proportional to the velocity gradient, ∂u/∂y, in the direction perpendicular to the layers.
Here, the constant η is known as the coefficient of viscosity, the viscosity, the dynamic viscosity, or the Newtonian viscosity. Many fluids, such as water and most gases, satisfy Newton's criterion and are known as Newtonian fluids. Non-Newtonian fluids exhibit a more complicated relationship between shear stress and velocity gradient than simple linearity.
The relationship between the shear stress and the velocity gradient can also be obtained by considering two plates closely spaced apart at a distance y, and separated by a homogeneous substance. Assuming that the plates are very large, with a large area A, such that edge effects may be ignored, and that the lower plate is fixed, let a force F be applied to the upper plate. If this force causes the substance between the plates to undergo shear flow (as opposed to just shearing elastically until the shear stress in the substance balances the applied force), the substance is called a fluid. The applied force is proportional to the area and velocity of the plate and inversely proportional to the distance between the plates. Combining these three relations results in the equation F = η(Au/y), where η is the proportionality factor called the absolute viscosity (with units Pa·s = kg/(m·s) or slugs/(ft·s)). The absolute viscosity is also known as the dynamic viscosity, and is often shortened to simply viscosity. The equation can be expressed in terms of shear stress; τ = F/A = η(u/y). The rate of shear deformation is u/y and can be also written as a shear velocity, du/dy. Hence, through this method, the relation between the shear stress and the velocity gradient can be obtained.
James Clerk Maxwell called viscosity fugitive elasticity because of the analogy that elastic deformation opposes shear stress in solids, while in viscous fluids, shear stress is opposed by rate of deformation.
# Viscosity Measurement
Dynamic viscosity is measured with various types of viscometer. Close temperature control of the fluid is essential to accurate measurements, particularly in materials like lubricants, whose viscosity can double with a change of only 5 °C. For some fluids, it is a constant over a wide range of shear rates. These are Newtonian fluids.
The fluids without a constant viscosity are called Non-Newtonian fluids. Their viscosity cannot be described by a single number. Non-Newtonian fluids exhibit a variety of different correlations between shear stress and shear rate.
One of the most common instruments for measuring kinematic viscosity is the glass capillary viscometer.
In paint industries, viscosity is commonly measured with a Zahn cup, in which the efflux time is determined and given to customers. The efflux time can also be converted to kinematic viscosities (cSt) through the conversion equations.
Also used in paint, a Stormer viscometer uses load-based rotation in order to determine viscosity. The viscosity is reported in Krebs units (KU), which are unique to Stormer viscometers.
Vibrating viscometers can also be used to measure viscosity. These models use vibration rather than rotation to measure viscosity.
Extensional viscosity can be measured with various rheometers that apply extensional stress
Volume viscosity can be measured with acoustic rheometer.
## Units of Measure
### Viscosity (dynamic/absolute viscosity)
Dynamic viscosity and absolute viscosity are synonymous. The IUPAC symbol for viscosity is the Greek symbol eta ({\eta}), and dynamic viscosity is also commonly referred to using the Greek symbol mu ({\mu}). The SI physical unit of dynamic viscosity is the pascal-second (Pa·s), which is identical to 1 kg·m−1·s−1. If a fluid with a viscosity of one Pa·s is placed between two plates, and one plate is pushed sideways with a shear stress of one pascal, it moves a distance equal to the thickness of the layer between the plates in one second.
The name poiseuille (Pl) was proposed for this unit (after Jean Louis Marie Poiseuille who formulated Poiseuille's law of viscous flow), but not accepted internationally. Care must be taken in not confusing the poiseuille with the poise named after the same person.
The cgs physical unit for dynamic viscosity is the poise (P), named after Jean Louis Marie Poiseuille. It is more commonly expressed, particularly in ASTM standards, as centipoise (cP). The centipoise is commonly used because water has a viscosity of 1.0020 cP (at 20 °C; the closeness to one is a convenient coincidence).
The relation between poise and pascal-seconds is:
### Kinematic viscosity
In many situations, we are concerned with the ratio of the viscous force to the inertial force, the latter characterised by the fluid density ρ. This ratio is characterised by the kinematic viscosity (\nu ), defined as follows:
where \mu is the (dynamic) viscosity, and \rho is the density.
Kinematic viscosity (Greek symbol: {\nu}) has SI units (m2·s−1). The cgs physical unit for kinematic viscosity is the stokes (abbreviated S or St), named after George Gabriel Stokes. It is sometimes expressed in terms of centistokes (cS or cSt). In U.S. usage, stoke is sometimes used as the singular form.
### Dynamic versus kinematic viscosity
Conversion between kinematic and dynamic viscosity, is given by \nu \rho = \eta.
For example,
A plot of the kinematic viscosity of air as a function of absolute temperature is available on the Internet.
### Example: viscosity of water
Because of its density of \rho = 1 g/cm3 (varies slightly with temperature), and its dynamic viscosity is near 1 mPa·s (see #Viscosity of water section), the viscosity values of water are, to rough precision, all powers of ten:
Dynamic viscosity:
Kinematic viscosity:
# Molecular origins
The viscosity of a system is determined by how molecules constituting the system interact. There are no simple but correct expressions for the viscosity of a fluid. The simplest exact expressions are the Green-Kubo relations for the linear shear viscosity or the Transient Time Correlation Function expressions derived by Evans and Morriss in 1985. Although these expressions are each exact in order to calculate the viscosity of a dense fluid, using these relations requires the use of molecular dynamics computer simulation.
## Gases
Viscosity in gases arises principally from the molecular diffusion that transports momentum between layers of flow. The kinetic theory of gases allows accurate prediction of the behavior of gaseous viscosity.
Within the regime where the theory is applicable:
- Viscosity is independent of pressure and
- Viscosity increases as temperature increases.
James Clerk Maxwell published a famous paper in 1866 using the kinetic theory of gases to study gaseous viscosity. (Reference: J.C. Maxwell, "On the viscosity or internal friction of air and other gases", Philosophical Transactions of the Royal Society of London, vol. 156 (1866), pp. 249-268.)
### Effect of temperature on the viscosity of a gas
Sutherland's formula can be used to derive the dynamic viscosity of an ideal gas as a function of the temperature:
where:
- {\eta} = viscosity in (Pa·s) at input temperature T
- {\eta}_0 = reference viscosity in (Pa·s) at reference temperature T_0
- T = input temperature in kelvin
- T_0 = reference temperature in kelvin
- C = Sutherland's constant for the gasous material in question
Valid for temperatures between 0 T < 555 K with an error due to pressure less than 10% below 3.45 MPa
Sutherland's constant and reference temperature for some gases
### Viscosity of a dilute gas
The Chapman-Enskog equation may be used to estimate viscosity for a dilute gas. This equation is based on semi-theorethical assumption by Chapman and Enskoq. The equation requires three empirically determined parameters: the collision diameter (σ), the maximum energy of attraction divided by the Boltzman constant (є/к) and the collision integral (ω(T*)).
- {\eta}_0 = viscosity for dilute gas (uP)
- M = molecular weight (kg/m^3)
- T = temperature (K)
- {\sigma} = the collision diameter (Å)
- {\epsilon}/{\kappa} = the maximum energy of attraction divided by the Boltzman constant (K)
- {\omega}_{\eta } = the collision integral
- T- = reduced temperature (K)
## Liquids
In liquids, the additional forces between molecules become important. This leads to an additional contribution to the shear stress though the exact mechanics of this are still controversial. Thus, in liquids:
- Viscosity is independent of pressure (except at very high pressure); and
- Viscosity tends to fall as temperature increases (for example, water viscosity goes from 1.79 cP to 0.28 cP in the temperature range from 0 °C to 100 °C); see temperature dependence of liquid viscosity for more details.
The dynamic viscosities of liquids are typically several orders of magnitude higher than dynamic viscosities of gases.
### Viscosity of blends of liquids
The viscosity of the blend of two or more liquids can be estimated using the Refutas equation. The calculation is carried out in three steps.
The first step is to calculate the Viscosity Blending Number (VBN) (also called the Viscosity Blending Index) of each component of the blend:
where v is the kinematic viscosity in centistokes (cSt). It is important that the kinematic viscosity of each component of the blend be obtained at the same temperature.
The next step is to calculate the VBN of the blend, using this equation:
where x_X is the mass fraction of each component of the blend.
Once the viscosity blending number of a blend has been calculated using equation (2), the final step is to determine the kinematic viscosity of the blend by solving equation (1) for v:
where VBN_{Blend} is the viscosity blending number of the blend.
# Viscosity of selected substances
The viscosity of air and water are by far the two most important materials for aviation aerodynamics and shipping fluid dynamics. Temperature plays the main role in determining viscosity.
## Viscosity of air
The viscosity of air depends mostly on the temperature.
At 15.0 °C, the viscosity of air is 1.78 × 10−5 kg/(m·s) or 1.78 × 10−4 cP. One can get the viscosity of air as a function of temperature from the Gas Viscosity Calculator
## Viscosity of water
The viscosity of water is 8.90 × 10−4 Pa·s or 8.90 × 10−3 dyn·s/cm2 or 10−1 cP at about 25 °C.
As a function of temperature T (K):
μ(Pa·s) = A × 10B/(T−C)
where A=2.414 × 10−5 Pa·s ; B = 247.8 K ; and C = 140 K.
## Viscosity of various materials
Some dynamic viscosities of Newtonian fluids are listed below:
Gases (at 0 °C):
Liquids (at 25 °C):
- Data from CRC Handbook of Chemistry and Physics, 73rd edition, 1992-1993.
Fluids with variable compositions, such as honey, can have a wide range of viscosities.
A more complete table can be found here, including the following:
- These materials are highly non-Newtonian.
# Viscosity of solids
On the basis that all solids flow to a small extent in response to shear stress some researchers have contended that substances known as amorphous solids, such as glass and many polymers, may be considered to have viscosity. This has led some to the view that solids are simply liquids with a very high viscosity, typically greater than 1012 Pa·s. This position is often adopted by supporters of the widely held misconception that glass flow can be observed in old buildings. This distortion is more likely the result of glass making process rather than the viscosity of glass.
However, others argue that solids are, in general, elastic for small stresses while fluids are not. Even if solids flow at higher stresses, they are characterized by their low-stress behavior. Viscosity may be an appropriate characteristic for solids in a plastic regime. The situation becomes somewhat confused as the term viscosity is sometimes used for solid materials, for example Maxwell materials, to describe the relationship between stress and the rate of change of strain, rather than rate of shear.
These distinctions may be largely resolved by considering the constitutive equations of the material in question, which take into account both its viscous and elastic behaviors. Materials for which both their viscosity and their elasticity are important in a particular range of deformation and deformation rate are called viscoelastic. In geology, earth materials that exhibit viscous deformation at least three times greater than their elastic deformation are sometimes called rheids.
# Viscosity of amorphous materials
Viscous flow in amorphous materials (e.g. in glasses and melts)
is a thermally activated process:
\eta = A \cdot e^{Q/RT}
where Q is activation energy, T is temperature, R is the molar gas constant and A is approximately a constant.
The viscous flow in amorphous materials is characterized by a deviation from the Arrhenius-type behavior: Q changes from a high value Q_H at low temperatures (in the glassy state) to a low value Q_L at high temperatures (in the liquid state). Depending on this change, amorphous materials are classified as either
- strong when: Q_H - Q_L or
- fragile when: Q_H - Q_L \ge Q_L
The fragility of amorphous materials is numerically characterized by the Doremus’ fragility ratio:
R_D = Q_H/Q_L
and strong material have R_D whereas fragile materials have R_D \ge 2
The viscosity of amorphous materials is quite exactly described by a two-exponential equation:
\eta = A_1 \cdot T \cdot \cdot
with constants A_1 , A_2 , B, C and D related to thermodynamic parameters of joining bonds of an amorphous material.
Not very far from the glass transition temperature, T_g, this equation can be approximated by a Vogel-Tammann-Fulcher (VTF) equation or a Kohlrausch-type stretched-exponential law.
If the temperature is significantly lower than the glass transition temperature, T\ll T_g\;, then the two-exponential equation simplifies to an Arrhenius type equation:
\eta = A \cdot e^{Q_H/RT}
with:
Q_H = H_d + H_m
where H_d is the enthalpy of formation of broken bonds (termed configurons) and H_m is the enthalpy of their motion.
When the temperature is less than the glass transition temperature, T , the activation energy of viscosity is high because the amorphous materials are in the glassy state and most of their joining bonds are intact.
If the temperature is highly above the glass transition temperature, T \gg Tg, the two-exponential equation also simplifies to an Arrhenius type equation:
\eta = A\cdot e^{Q_L/RT}
with:
Q_L = H_m
When the temperature is higher than the glass transition temperature, T > T_g, the activation energy of viscosity is low because amorphous materials are melt and have most of their joining bonds broken which facilitates flow.
# Volume (Bulk) viscosity
The negative-one-third of the trace of the stress tensor is often identified with the thermodynamic pressure,
-{1\over3}T_a^a = p,
which only depends upon the equilibrium state potentials like temperature and density (equation of state). In general, the trace of the stress tensor is the sum of thermodynamic pressure contribution plus another contribution which is proportional to the divergence of the velocity field. This constant of proportionality is called the volume viscosity.
# Eddy viscosity
In the study of turbulence in fluids, a common practical strategy for calculation is to ignore the small-scale vortices (or eddies) in the motion and to calculate a large-scale motion with an eddy viscosity that characterizes the transport and dissipation of energy in the smaller-scale flow (see large eddy simulation). Values of eddy viscosity used in modeling ocean circulation may be from 5x104 to 106 Pa·s depending upon the resolution of the numerical grid.
# Fluidity
The reciprocal of viscosity is fluidity, usually symbolized by \phi = 1/\eta or F=1/\eta, depending on the convention used, measured in reciprocal poise (cm·s·g-1), sometimes called the rhe. Fluidity is seldom used in engineering practice.
The concept of fluidity can be used to determine the viscosity of an ideal solution. For two components a and b, the fluidity when a and b are mixed is
which is only slightly simpler than the equivalent equation in terms of viscosity:
where \chi_a and \chi_b is the mole fraction of component a and b respectively, and \eta_a and \eta_b are the components pure viscosities.
# The linear viscous stress tensor
(See Hooke's law and strain tensor for an analogous development for linearly elastic materials.)
Viscous forces in a fluid are a function of the rate at which the fluid velocity is changing over distance. The velocity at any point \mathbf{r} is specified by the velocity field \mathbf{v}(\mathbf{r}). The velocity at a small distance d\mathbf{r} from point \mathbf{r} may be written as a Taylor series:
where \frac{d\mathbf{v}}{d\mathbf{r}} is shorthand for the dyadic product of the del operator and the velocity:
\frac{d\mathbf{v}}{d\mathbf{r}} = \begin{bmatrix}
\frac{\partial v_x}{\partial x} & \frac{\partial v_x}{\partial y} & \frac{\partial v_x}{\partial z}\\
\frac{\partial v_y}{\partial x} & \frac{\partial v_y}{\partial y} & \frac{\partial v_y}{\partial z}\\
\frac{\partial v_z}{\partial x} & \frac{\partial v_z}{\partial y}&\frac{\partial v_z}{\partial z}
\end{bmatrix}
This is just the Jacobian of the velocity field. Viscous forces are the result of relative motion between elements of the fluid, and so are expressible as a function of the velocity field. In other words, the forces at \mathbf{r} are a function of \mathbf{v}(\mathbf{r}) and all derivatives of \mathbf{v}(\mathbf{r}) at that point. In the case of linear viscosity, the viscous force will be a function of the Jacobian tensor alone. For almost all practical situations, the linear approximation is sufficient.
If we represent x, y, and z by indices 1, 2, and 3 respectively, the i,j component of the Jacobian may be written as \partial_i v_j where \partial_i is shorthand for \partial /\partial x_i. Note that when the first and higher derivative terms are zero, the velocity of all fluid elements is parallel, and there are no viscous forces.
Any matrix may be written as the sum of an antisymmetric matrix and a symmetric matrix, and this decomposition is independent of coordinate system, and so has physical significance. The velocity field may be approximated as:
where Einstein notation is now being used in which repeated indices in a product are implicitly summed. The second term from the right is the asymmetric part of the first derivative term, and it represents a rigid rotation of the fluid about \mathbf{r} with angular velocity \omega where:
\partial_2 v_3-\partial_3 v_2\\
\partial_3 v_1-\partial_1 v_3\\
\partial_1 v_2-\partial_2 v_1
\end{bmatrix}
For such a rigid rotation, there is no change in the relative positions of the fluid elements, and so there is no viscous force associated with this term. The remaining symmetric term is responsible for the viscous forces in the fluid. Assuming the fluid is isotropic (i.e. its properties are the same in all directions), then the most general way that the symmetric term (the rate-of-strain tensor) can be broken down in a coordinate-independent (and therefore physically real) way is as the sum of a constant tensor (the rate-of-expansion tensor) and a traceless symmetric tensor (the rate-of-shear tensor):
\frac{1}{2}\left(\partial_i v_j+\partial_j v_i\right)
\underbrace{\frac{1}{3}\partial_k v_k \delta_{ij}}_{\text{rate-of-expansion tensor}}
\underbrace{\left(\frac{1}{2}\left(\partial_i v_j+\partial_j v_i\right)-\frac{1}{3}\partial_k v_k \delta_{ij}\right)}_{\text{rate-of-shear tensor}}
where \delta_{ij} is the unit tensor. The most general linear relationship between the stress tensor \mathbf{\sigma} and the rate-of-strain tensor is then a linear combination of these two tensors:
\eta\left(\partial_i v_j+\partial_j v_i-\frac{2}{3}\partial_k v_k \delta_{ij}\right)
where \zeta is the coefficient of bulk viscosity (or "second viscosity") and \eta is the coefficient of (shear) viscosity.
The forces in the fluid are due to the velocities of the individual molecules. The velocity of a molecule may be thought of as the sum of the fluid velocity and the thermal velocity. The viscous stress tensor described above gives the force due to the fluid velocity only. The force on an area element in the fluid due to the thermal velocities of the molecules is just the hydrostatic pressure. This pressure term (-p\delta_{ij}) must be added to the viscous stress tensor to obtain the total stress tensor for the fluid.
The infinitesimal force dF_i on an infinitesimal area dA_i is then given by the usual relationship: | Viscosity
Template:Continuum mechanics
Viscosity is a measure of the resistance of a fluid to being deformed by either shear stress or extensional stress. It is commonly perceived as "thickness", or resistance to flow. Viscosity describes a fluid's internal resistance to flow and may be thought of as a measure of fluid friction. Thus, water is "thin", having a lower viscosity, while vegetable oil is "thick" having a higher viscosity. All real fluids (except superfluids) have some resistance to stress, but a fluid which has no resistance to shear stress is known as an ideal fluid or inviscid fluid.[1] The study of viscosity is known as rheology.
# Etymology
The word "viscosity" derives from the Latin word "viscum" for mistletoe. A viscous glue was made from mistletoe berries and used for lime-twigs to catch birds.[2]
# Viscosity coefficients
When looking at a value for viscosity, the number that one most often sees is the coefficient of viscosity. There are several different viscosity coefficients depending on the nature of applied stress and nature of the fluid. They are introduced in the main books on hydrodynamics[3][4] and rheology.[5]
- Dynamic viscosity determines the dynamics of an incompressible Newtonian fluid;
- Kinematic viscosity is the dynamic viscosity divided by the density for a Newtonian fluid;
- Volume viscosity determines the dynamics of a compressible Newtonian fluid;
- Bulk viscosity is the same as volume viscosity
- Shear viscosity is the viscosity coefficient when the applied stress is a shear stress (valid for non-Newtonian fluids);
- Extensional viscosity is the viscosity coefficient when the applied stress is an extensional stress (valid for non-Newtonian fluids).
Shear viscosity and dynamic viscosity are much better known than the others. That is why they are often referred to as simply viscosity.
Simply put, this quantity is the ratio between the pressure exerted on the surface of a fluid, in the lateral or horizontal direction, to the change in velocity of the fluid as you move down in the fluid (this is what is referred to as a velocity gradient). For example, at "room temperature", water has a nominal viscosity of 1.0 × 10-3 Pa∙s and motor oil has a nominal apparent viscosity of 250 × 10-3 Pa∙s.[6]
# Newton's theory
In general, in any flow, layers move at different velocities and the fluid's viscosity arises from the shear stress between the layers that ultimately opposes any applied force.
Isaac Newton postulated that, for straight, parallel and uniform flow, the shear stress, τ, between layers is proportional to the velocity gradient, ∂u/∂y, in the direction perpendicular to the layers.
Here, the constant η is known as the coefficient of viscosity, the viscosity, the dynamic viscosity, or the Newtonian viscosity. Many fluids, such as water and most gases, satisfy Newton's criterion and are known as Newtonian fluids. Non-Newtonian fluids exhibit a more complicated relationship between shear stress and velocity gradient than simple linearity.
The relationship between the shear stress and the velocity gradient can also be obtained by considering two plates closely spaced apart at a distance y, and separated by a homogeneous substance. Assuming that the plates are very large, with a large area A, such that edge effects may be ignored, and that the lower plate is fixed, let a force F be applied to the upper plate. If this force causes the substance between the plates to undergo shear flow (as opposed to just shearing elastically until the shear stress in the substance balances the applied force), the substance is called a fluid. The applied force is proportional to the area and velocity of the plate and inversely proportional to the distance between the plates. Combining these three relations results in the equation F = η(Au/y), where η is the proportionality factor called the absolute viscosity (with units Pa·s = kg/(m·s) or slugs/(ft·s)). The absolute viscosity is also known as the dynamic viscosity, and is often shortened to simply viscosity. The equation can be expressed in terms of shear stress; τ = F/A = η(u/y). The rate of shear deformation is <math>u/y</math> and can be also written as a shear velocity, du/dy. Hence, through this method, the relation between the shear stress and the velocity gradient can be obtained.
James Clerk Maxwell called viscosity fugitive elasticity because of the analogy that elastic deformation opposes shear stress in solids, while in viscous fluids, shear stress is opposed by rate of deformation.
# Viscosity Measurement
Dynamic viscosity is measured with various types of viscometer. Close temperature control of the fluid is essential to accurate measurements, particularly in materials like lubricants, whose viscosity can double with a change of only 5 °C. For some fluids, it is a constant over a wide range of shear rates. These are Newtonian fluids.
The fluids without a constant viscosity are called Non-Newtonian fluids. Their viscosity cannot be described by a single number. Non-Newtonian fluids exhibit a variety of different correlations between shear stress and shear rate.
One of the most common instruments for measuring kinematic viscosity is the glass capillary viscometer.
In paint industries, viscosity is commonly measured with a Zahn cup, in which the efflux time is determined and given to customers. The efflux time can also be converted to kinematic viscosities (cSt) through the conversion equations.
Also used in paint, a Stormer viscometer uses load-based rotation in order to determine viscosity. The viscosity is reported in Krebs units (KU), which are unique to Stormer viscometers.
Vibrating viscometers can also be used to measure viscosity. These models use vibration rather than rotation to measure viscosity.
Extensional viscosity can be measured with various rheometers that apply extensional stress
Volume viscosity can be measured with acoustic rheometer.
## Units of Measure
### Viscosity (dynamic/absolute viscosity)
Dynamic viscosity and absolute viscosity are synonymous. The IUPAC symbol for viscosity is the Greek symbol eta (<math>{\eta}</math>), and dynamic viscosity is also commonly referred to using the Greek symbol mu (<math>{\mu}</math>). The SI physical unit of dynamic viscosity is the pascal-second (Pa·s), which is identical to 1 kg·m−1·s−1. If a fluid with a viscosity of one Pa·s is placed between two plates, and one plate is pushed sideways with a shear stress of one pascal, it moves a distance equal to the thickness of the layer between the plates in one second.
The name poiseuille (Pl) was proposed for this unit (after Jean Louis Marie Poiseuille who formulated Poiseuille's law of viscous flow), but not accepted internationally. Care must be taken in not confusing the poiseuille with the poise named after the same person.
The cgs physical unit for dynamic viscosity is the poise[8] (P), named after Jean Louis Marie Poiseuille. It is more commonly expressed, particularly in ASTM standards, as centipoise (cP). The centipoise is commonly used because water has a viscosity of 1.0020 cP (at 20 °C; the closeness to one is a convenient coincidence).
The relation between poise and pascal-seconds is:
### Kinematic viscosity
In many situations, we are concerned with the ratio of the viscous force to the inertial force, the latter characterised by the fluid density ρ. This ratio is characterised by the kinematic viscosity (<math>\nu </math>), defined as follows:
where <math>\mu</math> is the (dynamic) viscosity, and <math>\rho</math> is the density.
Kinematic viscosity (Greek symbol: <math>{\nu}</math>) has SI units (m2·s−1). The cgs physical unit for kinematic viscosity is the stokes (abbreviated S or St), named after George Gabriel Stokes. It is sometimes expressed in terms of centistokes (cS or cSt). In U.S. usage, stoke is sometimes used as the singular form.
### Dynamic versus kinematic viscosity
Conversion between kinematic and dynamic viscosity, is given by <math>\nu \rho = \eta</math>.
For example,
A plot of the kinematic viscosity of air as a function of absolute temperature is available on the Internet.[9]
### Example: viscosity of water
Because of its density of <math>\rho</math> = 1 g/cm3 (varies slightly with temperature), and its dynamic viscosity is near 1 mPa·s (see #Viscosity of water section), the viscosity values of water are, to rough precision, all powers of ten:
Dynamic viscosity:
Kinematic viscosity:
# Molecular origins
The viscosity of a system is determined by how molecules constituting the system interact. There are no simple but correct expressions for the viscosity of a fluid. The simplest exact expressions are the Green-Kubo relations for the linear shear viscosity or the Transient Time Correlation Function expressions derived by Evans and Morriss in 1985. Although these expressions are each exact in order to calculate the viscosity of a dense fluid, using these relations requires the use of molecular dynamics computer simulation.
## Gases
Viscosity in gases arises principally from the molecular diffusion that transports momentum between layers of flow. The kinetic theory of gases allows accurate prediction of the behavior of gaseous viscosity.
Within the regime where the theory is applicable:
- Viscosity is independent of pressure and
- Viscosity increases as temperature increases.
James Clerk Maxwell published a famous paper in 1866 using the kinetic theory of gases to study gaseous viscosity. (Reference: J.C. Maxwell, "On the viscosity or internal friction of air and other gases", Philosophical Transactions of the Royal Society of London, vol. 156 (1866), pp. 249-268.)
### Effect of temperature on the viscosity of a gas
Sutherland's formula can be used to derive the dynamic viscosity of an ideal gas as a function of the temperature:
where:
- <math>{\eta}</math> = viscosity in (Pa·s) at input temperature <math>T</math>
- <math>{\eta}_0</math> = reference viscosity in (Pa·s) at reference temperature <math>T_0</math>
- <math>T</math> = input temperature in kelvin
- <math>T_0</math> = reference temperature in kelvin
- <math>C</math> = Sutherland's constant for the gasous material in question
Valid for temperatures between 0 < <math>T</math> < 555 K with an error due to pressure less than 10% below 3.45 MPa
Sutherland's constant and reference temperature for some gases
### Viscosity of a dilute gas
The Chapman-Enskog equation[10] may be used to estimate viscosity for a dilute gas. This equation is based on semi-theorethical assumption by Chapman and Enskoq. The equation requires three empirically determined parameters: the collision diameter (σ), the maximum energy of attraction divided by the Boltzman constant (є/к) and the collision integral (ω(T*)).
- <math> {\eta}_0 </math> = viscosity for dilute gas (uP)
- <math> M </math> = molecular weight (kg/m^3)
- <math> T </math> = temperature (K)
- <math> {\sigma}</math> = the collision diameter (Å)
- <math>{\epsilon}/{\kappa} </math> = the maximum energy of attraction divided by the Boltzman constant (K)
- <math> {\omega}_{\eta } </math> = the collision integral
- <math> T* </math> = reduced temperature (K)
## Liquids
In liquids, the additional forces between molecules become important. This leads to an additional contribution to the shear stress though the exact mechanics of this are still controversial.[citation needed] Thus, in liquids:
- Viscosity is independent of pressure (except at very high pressure); and
- Viscosity tends to fall as temperature increases (for example, water viscosity goes from 1.79 cP to 0.28 cP in the temperature range from 0 °C to 100 °C); see temperature dependence of liquid viscosity for more details.
The dynamic viscosities of liquids are typically several orders of magnitude higher than dynamic viscosities of gases.
### Viscosity of blends of liquids
The viscosity of the blend of two or more liquids can be estimated using the Refutas equation[11][12]. The calculation is carried out in three steps.
The first step is to calculate the Viscosity Blending Number (VBN) (also called the Viscosity Blending Index) of each component of the blend:
where v is the kinematic viscosity in centistokes (cSt). It is important that the kinematic viscosity of each component of the blend be obtained at the same temperature.
The next step is to calculate the VBN of the blend, using this equation:
where <math>x_X</math> is the mass fraction of each component of the blend.
Once the viscosity blending number of a blend has been calculated using equation (2), the final step is to determine the kinematic viscosity of the blend by solving equation (1) for v:
where <math>VBN_{Blend}</math> is the viscosity blending number of the blend.
# Viscosity of selected substances
The viscosity of air and water are by far the two most important materials for aviation aerodynamics and shipping fluid dynamics. Temperature plays the main role in determining viscosity.
## Viscosity of air
The viscosity of air depends mostly on the temperature.
At 15.0 °C, the viscosity of air is 1.78 × 10−5 kg/(m·s) or 1.78 × 10−4 cP. One can get the viscosity of air as a function of temperature from the Gas Viscosity Calculator
## Viscosity of water
The viscosity of water is 8.90 × 10−4 Pa·s or 8.90 × 10−3 dyn·s/cm2 or 10−1 cP at about 25 °C.
As a function of temperature T (K):
μ(Pa·s) = A × 10B/(T−C)
where A=2.414 × 10−5 Pa·s ; B = 247.8 K ; and C = 140 K.
## Viscosity of various materials
Some dynamic viscosities of Newtonian fluids are listed below:
Gases (at 0 °C):
Liquids (at 25 °C):
* Data from CRC Handbook of Chemistry and Physics, 73rd edition, 1992-1993.
Fluids with variable compositions, such as honey, can have a wide range of viscosities.
A more complete table can be found here, including the following:
* These materials are highly non-Newtonian.
# Viscosity of solids
On the basis that all solids flow to a small extent in response to shear stress some researchers[14][15] have contended that substances known as amorphous solids, such as glass and many polymers, may be considered to have viscosity. This has led some to the view that solids are simply liquids with a very high viscosity, typically greater than 1012 Pa·s. This position is often adopted by supporters of the widely held misconception that glass flow can be observed in old buildings. This distortion is more likely the result of glass making process rather than the viscosity of glass.[16]
However, others argue that solids are, in general, elastic for small stresses while fluids are not.[17] Even if solids flow at higher stresses, they are characterized by their low-stress behavior. Viscosity may be an appropriate characteristic for solids in a plastic regime. The situation becomes somewhat confused as the term viscosity is sometimes used for solid materials, for example Maxwell materials, to describe the relationship between stress and the rate of change of strain, rather than rate of shear.
These distinctions may be largely resolved by considering the constitutive equations of the material in question, which take into account both its viscous and elastic behaviors. Materials for which both their viscosity and their elasticity are important in a particular range of deformation and deformation rate are called viscoelastic. In geology, earth materials that exhibit viscous deformation at least three times greater than their elastic deformation are sometimes called rheids.
# Viscosity of amorphous materials
Viscous flow in amorphous materials (e.g. in glasses and melts)
[19][20][21] is a thermally activated process:
<math>\eta = A \cdot e^{Q/RT}</math>
where <math>Q</math> is activation energy, <math>T</math> is temperature, <math>R</math> is the molar gas constant and <math>A</math> is approximately a constant.
The viscous flow in amorphous materials is characterized by a deviation from the Arrhenius-type behavior: <math>Q</math> changes from a high value <math>Q_H</math> at low temperatures (in the glassy state) to a low value <math>Q_L</math> at high temperatures (in the liquid state). Depending on this change, amorphous materials are classified as either
- strong when: <math>Q_H - Q_L < Q_L</math> or
- fragile when: <math>Q_H - Q_L \ge Q_L</math>
The fragility of amorphous materials is numerically characterized by the Doremus’ fragility ratio:
<math>R_D = Q_H/Q_L</math>
and strong material have <math>R_D < 2\;</math> whereas fragile materials have <math>R_D \ge 2</math>
The viscosity of amorphous materials is quite exactly described by a two-exponential equation:
<math>\eta = A_1 \cdot T \cdot [1 + A_2 \cdot e^{B/RT}] \cdot [1 + C \cdot e^{D/RT}]</math>
with constants <math>A_1 , A_2 , B, C</math> and <math>D</math> related to thermodynamic parameters of joining bonds of an amorphous material.
Not very far from the glass transition temperature, <math>T_g</math>, this equation can be approximated by a Vogel-Tammann-Fulcher (VTF) equation or a Kohlrausch-type stretched-exponential law.
If the temperature is significantly lower than the glass transition temperature, <math>T\ll T_g\;</math>, then the two-exponential equation simplifies to an Arrhenius type equation:
<math>\eta = A \cdot e^{Q_H/RT}</math>
with:
<math>Q_H = H_d + H_m</math>
where <math>H_d</math> is the enthalpy of formation of broken bonds (termed configurons) and <math>H_m</math> is the enthalpy of their motion.
When the temperature is less than the glass transition temperature, <math>T < T_g</math>, the activation energy of viscosity is high because the amorphous materials are in the glassy state and most of their joining bonds are intact.
If the temperature is highly above the glass transition temperature, <math>T \gg Tg</math>, the two-exponential equation also simplifies to an Arrhenius type equation:
<math>\eta = A\cdot e^{Q_L/RT}</math>
with:
<math>Q_L = H_m</math>
When the temperature is higher than the glass transition temperature, <math>T > T_g</math>, the activation energy of viscosity is low because amorphous materials are melt and have most of their joining bonds broken which facilitates flow.
# Volume (Bulk) viscosity
The negative-one-third of the trace of the stress tensor is often identified with the thermodynamic pressure,
<math>-{1\over3}T_a^a = p</math>,
which only depends upon the equilibrium state potentials like temperature and density (equation of state). In general, the trace of the stress tensor is the sum of thermodynamic pressure contribution plus another contribution which is proportional to the divergence of the velocity field. This constant of proportionality is called the volume viscosity.
# Eddy viscosity
In the study of turbulence in fluids, a common practical strategy for calculation is to ignore the small-scale vortices (or eddies) in the motion and to calculate a large-scale motion with an eddy viscosity that characterizes the transport and dissipation of energy in the smaller-scale flow (see large eddy simulation). Values of eddy viscosity used in modeling ocean circulation may be from 5x104 to 106 Pa·s depending upon the resolution of the numerical grid.
# Fluidity
The reciprocal of viscosity is fluidity, usually symbolized by <math>\phi = 1/\eta</math> or <math>F=1/\eta</math>, depending on the convention used, measured in reciprocal poise (cm·s·g-1), sometimes called the rhe. Fluidity is seldom used in engineering practice.
The concept of fluidity can be used to determine the viscosity of an ideal solution. For two components <math>a</math> and <math>b</math>, the fluidity when <math>a</math> and <math>b</math> are mixed is
which is only slightly simpler than the equivalent equation in terms of viscosity:
where <math>\chi_a</math> and <math>\chi_b</math> is the mole fraction of component <math>a</math> and <math>b</math> respectively, and <math>\eta_a</math> and <math>\eta_b</math> are the components pure viscosities.
# The linear viscous stress tensor
(See Hooke's law and strain tensor for an analogous development for linearly elastic materials.)
Viscous forces in a fluid are a function of the rate at which the fluid velocity is changing over distance. The velocity at any point <math>\mathbf{r}</math> is specified by the velocity field <math>\mathbf{v}(\mathbf{r})</math>. The velocity at a small distance <math>d\mathbf{r}</math> from point <math>\mathbf{r}</math> may be written as a Taylor series:
where <math>\frac{d\mathbf{v}}{d\mathbf{r}}</math> is shorthand for the dyadic product of the del operator and the velocity:
<math>\frac{d\mathbf{v}}{d\mathbf{r}} = \begin{bmatrix}
\frac{\partial v_x}{\partial x} & \frac{\partial v_x}{\partial y} & \frac{\partial v_x}{\partial z}\\
\frac{\partial v_y}{\partial x} & \frac{\partial v_y}{\partial y} & \frac{\partial v_y}{\partial z}\\
\frac{\partial v_z}{\partial x} & \frac{\partial v_z}{\partial y}&\frac{\partial v_z}{\partial z}
\end{bmatrix}
</math>
This is just the Jacobian of the velocity field. Viscous forces are the result of relative motion between elements of the fluid, and so are expressible as a function of the velocity field. In other words, the forces at <math>\mathbf{r}</math> are a function of <math>\mathbf{v}(\mathbf{r})</math> and all derivatives of <math>\mathbf{v}(\mathbf{r})</math> at that point. In the case of linear viscosity, the viscous force will be a function of the Jacobian tensor alone. For almost all practical situations, the linear approximation is sufficient.
If we represent x, y, and z by indices 1, 2, and 3 respectively, the i,j component of the Jacobian may be written as <math>\partial_i v_j</math> where <math>\partial_i</math> is shorthand for <math>\partial /\partial x_i</math>. Note that when the first and higher derivative terms are zero, the velocity of all fluid elements is parallel, and there are no viscous forces.
Any matrix may be written as the sum of an antisymmetric matrix and a symmetric matrix, and this decomposition is independent of coordinate system, and so has physical significance. The velocity field may be approximated as:
where Einstein notation is now being used in which repeated indices in a product are implicitly summed. The second term from the right is the asymmetric part of the first derivative term, and it represents a rigid rotation of the fluid about <math>\mathbf{r}</math> with angular velocity <math>\omega</math> where:
\partial_2 v_3-\partial_3 v_2\\
\partial_3 v_1-\partial_1 v_3\\
\partial_1 v_2-\partial_2 v_1
\end{bmatrix}
</math>
For such a rigid rotation, there is no change in the relative positions of the fluid elements, and so there is no viscous force associated with this term. The remaining symmetric term is responsible for the viscous forces in the fluid. Assuming the fluid is isotropic (i.e. its properties are the same in all directions), then the most general way that the symmetric term (the rate-of-strain tensor) can be broken down in a coordinate-independent (and therefore physically real) way is as the sum of a constant tensor (the rate-of-expansion tensor) and a traceless symmetric tensor (the rate-of-shear tensor):
\frac{1}{2}\left(\partial_i v_j+\partial_j v_i\right)
=
\underbrace{\frac{1}{3}\partial_k v_k \delta_{ij}}_{\text{rate-of-expansion tensor}}
+
\underbrace{\left(\frac{1}{2}\left(\partial_i v_j+\partial_j v_i\right)-\frac{1}{3}\partial_k v_k \delta_{ij}\right)}_{\text{rate-of-shear tensor}}
</math>
where <math>\delta_{ij}</math> is the unit tensor. The most general linear relationship between the stress tensor <math>\mathbf{\sigma}</math> and the rate-of-strain tensor is then a linear combination of these two tensors:[22]
\eta\left(\partial_i v_j+\partial_j v_i-\frac{2}{3}\partial_k v_k \delta_{ij}\right)
</math>
where <math>\zeta</math> is the coefficient of bulk viscosity (or "second viscosity") and <math>\eta</math> is the coefficient of (shear) viscosity.
The forces in the fluid are due to the velocities of the individual molecules. The velocity of a molecule may be thought of as the sum of the fluid velocity and the thermal velocity. The viscous stress tensor described above gives the force due to the fluid velocity only. The force on an area element in the fluid due to the thermal velocities of the molecules is just the hydrostatic pressure. This pressure term (<math>-p\delta_{ij}</math>) must be added to the viscous stress tensor to obtain the total stress tensor for the fluid.
The infinitesimal force <math>dF_i</math> on an infinitesimal area <math>dA_i</math> is then given by the usual relationship: | https://www.wikidoc.org/index.php/Pascal-second | |
9c0a8c6a161430d365e1d2c77d02d6e24fe2736a | wikidoc | Pyromania | Pyromania
Synonyms and keywords: Impulse control disorder
# Overview
Pyromania is an intense obsession with fire, explosives, and their related effects. It is also an obsession with starting fires in an intentional fashion. An individual with pyromania is referred to as a pyromaniac or "pyro" for short. In colloquial English, the synonyms "firebug" and "firestarter" are sometimes used. Pyromaniacs are identified specifically as not having any other symptoms but obsession with fire causing their behavior. It is distinct from arson, and pyromaniacs are also distinct from those who start fires because of psychosis, for personal, monetary or political gain, or for acts of revenge. Pyromaniacs start fires to induce euphoria, and often tend to fixate on institutions of fire control like fire stations and firefighters.
# Historical Perspective
Starting in 1850, Devin Amaercer started eight fires and developed this disease. There have been many arguments as to the cause of pyromania. Whether the condition arises from mental illness or moral deficiency has changed depending on the development of psychiatry and mental health care in general.
# Pathophysiology
Little is known about this impulse control disorder, except some research suggesting there is an environmental component arising in late childhood.
Few scientifically rigorous studies have been done on the subject, but psychosocial hypotheses suggest pyromania may be a form of communication from those with few social skills, or an ungratified sexuality for which setting fires is a symbolic solution. Medical research also suggests a possible link to reactive hypoglycemia or a decreased concentration of 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid. Some biological similarities have been discovered, such as abnormalities in the levels of the neurotransmitters norepinephrine and serotonin, which could be related to problems of impulse control, and also low blood sugar levels. Children who are pyromaniacs often have a history of cruelty to animals. They also frequently suffer from other behavior disorders and have learning disabilities and attention disorders. It is also one of the supposed three early signs of developing psychopathy (the MacDonald Triad). Other studies have linked pyromania to child abuse.
# Differential Diagnosis
- Antisocial personality disorder
- Conduct disorder
- Delusion
- Developmental experimentation in childhood (playing with matches, lighters, or fire)
- Epilepsy
- Hallucination
- Impaired judgment
- Manic episode
# Epidemiology and Demographics
## Prevalence
The prevalence of pyromania in the overall population is unknown. Pyromania is a very rare disorder, and the incident of it is less than one percent in most studies; also, pyromaniacs are a very small proportion of psychiatric hospital admissions. Pyromania can occur in children as young as age three, but it is rare in adults and rarer in children. Only a small percentage of children and adolescents arrested for arson have pyromania. Ninety percent of those diagnosed with Pyromania are male. Based on a survey of 9282 Americans using the Diagnostic & Statistical Manual on Mental Disorders, 4th edition, impulse-control problems such as gambling, pyromania and compulsive shopping collectively affect 9% of the population. And a 1979 study by the Law Enforcement Assistance Administration found that only 14 percent of fires were started by pyromaniacs and others with mental illness.
# Risk Factors
- Learning difficulties
- Male gender
- Poor social skills
# Diagnosis
## Symptoms
Pyromaniacs are known to have feelings of sadness and loneliness, followed by rage, which leads to the setting of fires as an outlet. For a positive diagnosis, there must be purposeful setting of fire on at least two occasions. There is tension or arousal prior to the act, and gratification or relief when it is over. It is done for its own sake, and not for any other motivation. In some cases it is all about the pleasure of seeing what other people have to do to extinguish the fire, and the pyromaniac may enjoy reading of the effects of what they have done. Many sufferers claim that they just like to set fires for the sake of fires and the blaze of dancing flames. Many pyromaniacs feel a relief of stress in watching things burn or smolder, and the condition is fueled by the need to watch objects burn.
A lot of people diagnosed with pyromania have also committed other crimes such as, forcible rape (11%), nonviolent sexual offenses (18%) and vandalism of property (19%).
# Diagnostic Criteria
## DSM-V Diagnostic Criteria for Pyromania
# Treatment
Behavior modification is the usual treatment for pyromania. Other treatments include seeing the patient's actions as an unconscious process and analyzing it to help the patient get rid of the behavior. Often, this treatment is followed by a more psychodynamic approach that addresses the underlying problems that generated the negative emotions causing the mania. The prognosis for treatment is generally fair to poor. Treatment appears to work in 95% of children that exhibit signs of pyromania, which include family therapy and community intervention. Selective serotonin reuptake inhibitors (SSRIs) are also used to treat this condition. Studies have also shown there are therapeutic benefits associated with playing out the mania in a simulated environment.
File:Http installer/Rammstein 1 - London UK 2305 large.6927855.jpg | Pyromania
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
Synonyms and keywords: Impulse control disorder
# Overview
Pyromania is an intense obsession with fire, explosives, and their related effects. It is also an obsession with starting fires in an intentional fashion. An individual with pyromania is referred to as a pyromaniac or "pyro" for short. In colloquial English, the synonyms "firebug" and "firestarter" are sometimes used. Pyromaniacs are identified specifically as not having any other symptoms but obsession with fire causing their behavior. It is distinct from arson, and pyromaniacs are also distinct from those who start fires because of psychosis, for personal, monetary or political gain, or for acts of revenge. Pyromaniacs start fires to induce euphoria, and often tend to fixate on institutions of fire control like fire stations and firefighters.
# Historical Perspective
Starting in 1850, Devin Amaercer started eight fires and developed this disease. There have been many arguments as to the cause of pyromania. Whether the condition arises from mental illness or moral deficiency has changed depending on the development of psychiatry and mental health care in general.[1]
# Pathophysiology
Little is known about this impulse control disorder, except some research suggesting there is an environmental component arising in late childhood.[2]
Few scientifically rigorous studies have been done on the subject, but psychosocial hypotheses suggest pyromania may be a form of communication from those with few social skills, or an ungratified sexuality for which setting fires is a symbolic solution. Medical research also suggests a possible link to reactive hypoglycemia or a decreased concentration of 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid.[3] Some biological similarities have been discovered, such as abnormalities in the levels of the neurotransmitters norepinephrine and serotonin, which could be related to problems of impulse control, and also low blood sugar levels.[4] Children who are pyromaniacs often have a history of cruelty to animals. They also frequently suffer from other behavior disorders and have learning disabilities and attention disorders. It is also one of the supposed three early signs of developing psychopathy (the MacDonald Triad). [4] Other studies have linked pyromania to child abuse. [4]
# Differential Diagnosis
- Antisocial personality disorder
- Conduct disorder
- Delusion
- Developmental experimentation in childhood (playing with matches, lighters, or fire)
- Epilepsy
- Hallucination
- Impaired judgment
- Manic episode [5]
# Epidemiology and Demographics
## Prevalence
The prevalence of pyromania in the overall population is unknown.[5] Pyromania is a very rare disorder, and the incident of it is less than one percent in most studies; also, pyromaniacs are a very small proportion of psychiatric hospital admissions.[6] Pyromania can occur in children as young as age three, but it is rare in adults and rarer in children. Only a small percentage of children and adolescents arrested for arson have pyromania. Ninety percent of those diagnosed with Pyromania are male.[4] Based on a survey of 9282 Americans using the Diagnostic & Statistical Manual on Mental Disorders, 4th edition, impulse-control problems such as gambling, pyromania and compulsive shopping collectively affect 9% of the population.[7] And a 1979 study by the Law Enforcement Assistance Administration found that only 14 percent of fires were started by pyromaniacs and others with mental illness.[8]
# Risk Factors
- Learning difficulties
- Male gender
- Poor social skills[5]
# Diagnosis
## Symptoms
Pyromaniacs are known to have feelings of sadness and loneliness, followed by rage, which leads to the setting of fires as an outlet.[4] For a positive diagnosis, there must be purposeful setting of fire on at least two occasions. There is tension or arousal prior to the act, and gratification or relief when it is over. It is done for its own sake, and not for any other motivation. [9] In some cases it is all about the pleasure of seeing what other people have to do to extinguish the fire, and the pyromaniac may enjoy reading of the effects of what they have done. [4] Many sufferers claim that they just like to set fires for the sake of fires and the blaze of dancing flames. Many pyromaniacs feel a relief of stress in watching things burn or smolder, and the condition is fueled by the need to watch objects burn.
A lot of people diagnosed with pyromania have also committed other crimes such as, forcible rape (11%), nonviolent sexual offenses (18%) and vandalism of property (19%).[10]
# Diagnostic Criteria
## DSM-V Diagnostic Criteria for Pyromania[5]
# Treatment
Behavior modification is the usual treatment for pyromania. Other treatments include seeing the patient's actions as an unconscious process and analyzing it to help the patient get rid of the behavior. Often, this treatment is followed by a more psychodynamic approach that addresses the underlying problems that generated the negative emotions causing the mania.[4] The prognosis for treatment is generally fair to poor.[2] Treatment appears to work in 95% of children that exhibit signs of pyromania, which include family therapy and community intervention. Selective serotonin reuptake inhibitors (SSRIs) are also used to treat this condition. Studies have also shown there are therapeutic benefits associated with playing out the mania in a simulated environment.[4]
File:Http://i.realone.com/assets/rn/rs/2005/games installer/Rammstein 1 - London UK 2305 large.6927855.jpg | https://www.wikidoc.org/index.php/Pathological_fire-setting | |
ae284699b1b5ea7106b6ef08d089d64d2ed1adfd | wikidoc | Pathology | Pathology
Pathology is the study and diagnosis of disease through examination of organs, tissues, cells and bodily fluids. The term encompasses both the medical specialty which uses tissues and body fluids to obtain clinically useful information, as well as the related scientific study of disease processes.
# History
The histories of both experimental and medical pathology can be traced to the earliest application of the scientific method to the field of medicine, a development which occurred in Western Europe during the Italian Renaissance. Most early pathologists were also practicing physicians or surgeons. Like other medical fields, pathology has become more specialized with time, and most pathologists today do not practice in other areas of medicine.
## Origins of pathology
The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may seem obvious today, but there are few if any recorded examples of true autopsies performed prior to the Renaissance. The first physician known to have repeatedly used anatomic dissection to determine cause of death was an Italian, Antonio Benivieni (1443-1502). Perhaps the most famous early gross pathologist was Giovanni Morgagni (1682-1771). His magnum opus, De Sedibus et Causis Morborum per Anatomem Indagatis, published in 1761, describes the findings of over 600 partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients prior to their demise. Although the study of normal anatomy was already well advanced at this date, De Sedibus was one of the first treatises specifically devoted to the corrolation of diseased anatomy with clinical illness. By the late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases. The extent of gross pathology research in this period can be epitomized by the work of the Viennese pathologist (originally from Hradec Kralove in the Czech Rep.) Carl Rokitansky (1804-1878), who is said to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime .
## Origins of microscopic pathology
Rudolf Virchow (1821-1902) is generally recognized to be the father of microscopic pathology. While the compound microscope had been invented approximately 150 years prior, Virchow was one of the first prominent physicians to emphasize the study of manifestations of disease which were visible only at the cellular level. A student of Virchow's, Julius Cohnheim (1839-1884) combined histology techniques with experimental manipulations to study inflammation, making him one of the earliest experimental pathologists. Cohnheim also pioneered the use of the frozen section; a version of this technique is widely employed by modern pathologists to render diagnoses and provide other clinical information intraoperatively.
## Modern experimental pathology
As new research techniques, such as electron microscopy, immunohistochemistry, and molecular biology have expanded the means by which biomedical scientists can study disease, the definition and boundaries of investigative pathology have become less distinct. In the broadest sense, nearly all research which links manifestations of disease to identifiable processes in cells, tissues, or organs can be considered experimental pathology.
# Pathology as a science
Pathology is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the body's means of responding to and repairing injury. Disease processes may be incited or exacerbated by a variety of external and internal influences, including trauma, infection, poisoning, loss of blood flow, autoimmunity, inherited or acquired genetic damage, or errors of development. One common theme in pathology is the way in which the body's responses to injury, while evolved to protect health, can also contribute in some ways to disease processes. Elucidation of general principles underlying pathologic processes, such as cellular adaptation to injury, cell death, inflammation, tissue repair, and neoplasia, creates a conceptual framework with which to analyze and understand specific human diseases.
## Adaptation to injury
Cells and tissues may respond to injury and stress by specific mechanisms, which may vary according to the cell types and nature of the injury. In the short term, cells may activate specific genetic programs to protect their vital proteins and organelles from heat shock or hypoxia, and may activate DNA repair pathways to repair damage to chromosomes from radiation or chemicals. Hyperplasia is a long-term adaptive response of cell division and multiplication, which can increase the ability of a tissue to compensate for an injury. For example, repeated irritation to the skin can cause a protective thickening due to hyperplasia of the epidermis. Hypertrophy is an increase in the size of cells in a tissue in response to stress, an example being hypertrophy of muscle cells in the heart in response to increased resistance to blood flow as a result of narrowing of the heart's outflow valve. Metaplasia occurs when repeated damage to the cellular lining of an organ triggers its replacement by a different cell type.
## Cell death
Necrosis is the irreversible destruction of cells as a result of severe injury in a setting where the cell is unable to activate the needed metabolic pathways for survival or orderly degeneration. This is often due to external pathologic factors, such as toxins or loss of oxygen supply. Milder stresses may lead to a process called reversible cell injury, which mimics the cell swelling and vacuolization seen early in the necrotic process, but in which the cell is able to adapt and survive. In necrosis, the components of degenerating cells leak out, potentially contributing to inflammation and further damage. Apoptosis, in contrast, is a regulated, orderly degeneration of the cell which occurs in the settings of both injury and normal physiological processes.
## Inflammation
Inflammation is a particularly important and complex reaction to tissue injury, and is particularly important in fighting infection. Acute inflammation is generally a non-specific response triggered by the injured tissue cells themselves, as well as specialized cells of the innate immune system and previously developed adaptive immune mechanisms. A localized acute inflammatory response triggers vascular changes in the injured area, recruits pathogen-fighting neutrophils, and begins the process of developing a new adaptive immune response. Chronic inflammation occurs when the acute response fails to entirely clear the inciting factor. While chronic inflammation can lay a positive role in containing a continuing infectious hazard, it can also lead to progressive tissue damage, as well as predisposing (in some cases) to the development of cancer.
## Tissue repair
Tissue repair, as seen in wound healing, is triggered by inflammation. The process may proceed even before the resolution of a precipitating insult, through the formation of granulation tissue. Healing involves the proliferation of connective tissue cells and blood vessel-forming cells as a result of hormonal growth signals. While healing is a critical adaptive response, an aberrent healing response can lead to progressive fibrosis, contractures, or other changes which can compromise function.
## Neoplasia
Neoplasia, or "new growth," is a proliferation of cells which is independent of any physiological process. The most familiar examples of neoplasia are benign tumors and cancers. Neoplasia results from genetic changes which cause cells to activate genetic programs inappropriately. Dysplasia is an early sign of a neoplastic process in a tissue, and is marked by persistence of immature, poorly differentiated cell forms. Interestingly, there are many similarities in the gene pathways activated in cancer cells, and those activated in cells involved in wound healing and inflammation.
# Pathology as a medical specialty
Physicians who practice pathology diagnose and characterize disease in living patients by examining biopsies and other specimens. For example, the vast majority of cancer diagnoses are made or confirmed by a pathologist. Pathologists may also conduct autopsies to investigate causes of death. The medical practice of pathology grew out the tradition of investigative pathology, and many of the academic leaders in pathology today are accomplished in both basic science research and diagnostic practice. However, as with other specialties in medicine, most modern physician-pathologists are employed in full-time practice, and do not perform original research.
Pathology is a unique medical specialty in that pathologists typically do not see patients directly, but rather serve as consultants to other physicians (often referred to as "clinicians" within the pathology community). However, in the United States and in many other countries, pathologists receive the same doctorate training, and undergo the same medical licensure process as other physicians. Pathology is a diverse field, and the organization of subspecialties within pathology vary between nations.
## Anatomical Pathology
Anatomical pathologists diagnose disease and gain other clinically significant information through the examination of tissues and cells. This generally involves gross and microscopic visual examination of tissues, with special stains and immunohistochemistry employed to visualize specific proteins and other substances in and around cells. More recently, anatomical pathologists have begun to employ molecular biology techniques to gain additional clinical information from these same specimens. Anatomic pathologists serve as the definitive diagnosticians for most cancers, as well as numerous other diseases.
- Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.
- Cytopathology is concerned with the microscopic examination of whole, individual cells obtained from smears or fine needle aspirates.
- Molecular pathology refers to the use of nucleic acid-based techniques, such as in-situ hybridization, reverse-transcriptase polymerase chain reaction, and nucleic acid microarrays for specialised diagnostic studies of disease in tissues and cells.
- Autopsies are used to provide definitive evidence of the disease processes contributing to a person's death.
- Forensic pathology receive specialized training in determining the cause of death and other legally relevant information from the bodies of persons who died in a non-medical or potentially criminal circumstances.
## Clinical pathology
Clinical pathology, also known as laboratory medicine, is the medical specialty concerned with diagnosing diseases based on the analysis of body fluids, such as plasma, urine, stool, respiratory or mucosal secretions, inflammatory exudates, and pleural, pericardial, peritoneal, synovial, or cerebrospinal fluid. The practice of clinical pathology is centered around the clinical laboratory. In modern clinical laboratories, many routine studies are largely automated. The clinical pathologist is responsible for overseeing the work of laboratory technicians, performing quality assurance to assure the validity of test results, performing interpretations of more complex studies, and serving as a consultant to clinicians so that the most appropriate studies can be performed for the diagnosis or assessment of an individual patient's condition. In some areas, non-pathologists, such as other physicians or Ph.D.'s may run clinical labs and perform functions within those specific labs which are similar to the role of a board-certified clinical pathologist.
Sub-specialties within clinical pathology include the following:
- Clinical chemistry (A board-certifiable subspecialty, chemical pathology, in the U.S.)
- Hematology and Flow cytometry (Part of a board-certifiable subspecialty, hematology, in the U.S.)
- Blood banking/Transfusion medicine (A board-certifiable subspecialty in the U.S.)
- Medical microbiology (A board-certifiable subspecialty in the U.S.)
- Medical cytogenetics
- Immunology
- Molecular genetic pathology (A board-certifiable subspecialty in the U.S.)
## Dental pathology
In the United States, subspecialty-trained doctors of dental surgery (D.D.S), rather than medical doctors, can be certified by a professional board to practice dental pathology.
# Training of medical pathologists
## Pathology in the United States
In the United States, pathologists are medical doctors (M.D.) or doctors of osteopathic medicine (D.O.), that have completed a four-year undergraduate program, four years of medical school training, and three to four years of postgraduate training in the form of a pathology residency. Training may be within two primary specialties, as recognized by the American Board of Pathology: Anatomic Pathology, and Clinical Pathology, each of which requires separate board certification. Many pathologists seek a broad-based training and become certified in both fields. These skills are complementary in many hospital-based private practice settings, since the day-to-day work of many clinical laboratories only requires the intermittent attention of a physician. Thus, pathologists are able to spend much of their time evaluating anatomic pathology cases, while remaining available to cover any special issues which might arise in the clinical laboratories. Pathologists may pursue specialised fellowship training within one or more sub-specialties of either anatomic or clinical pathology. Some of these sub-specialities permit additional board certification, while others do not.
## Pathology in the United Kingdom
In the UK pathologists are medical doctors registered with the UK General Medical Council. They will have completed an undergraduate medical education which in most countries lasts 4-6 years. The training to become a pathologist is under the oversight of the Royal College of Pathologists. Typically a one year training attachment is followed by an aptitude test. This is followed by further specialist training in surgical pathology, cytopathology, and post mortem pathology. There are two examinations run by the Royal College of Pathologists termed Part 1 and Part 2. The Part 2 examination is designed to test competence to work as an independent practitioner in pathology and is typically taken after 5 years specialist training. All post-graduate medical training and education in the UK is overseen by the Postgraduate Medical Education and Training Board. It is possible to take a specialist part 2 examination in paediatric pathology or neuropathology. It is possible to take a special diploma in dermatopathology or cytopathology, recognising additional specialist training and expertise.
# Non-human pathology
Veterinary pathologists are veterinary practitioners who specialise in the diagnosis and characterization of veterinary diseases through the examination of animal tissue and body fluids. Veterinary pathologists are veterinarians with advanced training (board certification or Ph.D.) in either diagnostic pathology or research into the biological processes underlying disease (pathobiology). Diagnostic veterinary pathologists are further subcategorized as either anatomical pathologists or clinical pathologists. Clinical pathologists examine specimens such as blood, excretions or biopsy material to diagnose disease in living animals. Anatomical pathologists utilize post mortem examinations of dead animals to arrive at a diagnosis. Post mortem examinations entail a necropsy (an animal autopsy), histopathologic (microscopic) study of tissue specimens collected at the necropsy and sometimes specialized studies (radiographic, toxicologic, etc.)
Plant pathologists are specialized scientists who investigate the causes of diseases in plants. | Pathology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9]
Pathology is the study and diagnosis of disease through examination of organs, tissues, cells and bodily fluids. The term encompasses both the medical specialty which uses tissues and body fluids to obtain clinically useful information, as well as the related scientific study of disease processes.
# History
The histories of both experimental and medical pathology can be traced to the earliest application of the scientific method to the field of medicine, a development which occurred in Western Europe during the Italian Renaissance.[1] Most early pathologists were also practicing physicians or surgeons. Like other medical fields, pathology has become more specialized with time, and most pathologists today do not practice in other areas of medicine.
## Origins of pathology
The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may seem obvious today, but there are few if any recorded examples of true autopsies performed prior to the Renaissance. The first physician known to have repeatedly used anatomic dissection to determine cause of death was an Italian, Antonio Benivieni (1443-1502).[1] Perhaps the most famous early gross pathologist was Giovanni Morgagni (1682-1771). His magnum opus, De Sedibus et Causis Morborum per Anatomem Indagatis, published in 1761, describes the findings of over 600 partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients prior to their demise. Although the study of normal anatomy was already well advanced at this date, De Sedibus was one of the first treatises specifically devoted to the corrolation of diseased anatomy with clinical illness.[2][3] By the late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases. The extent of gross pathology research in this period can be epitomized by the work of the Viennese pathologist (originally from Hradec Kralove in the Czech Rep.) Carl Rokitansky (1804-1878), who is said to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime .[1][4]
## Origins of microscopic pathology
Rudolf Virchow (1821-1902) is generally recognized to be the father of microscopic pathology. While the compound microscope had been invented approximately 150 years prior, Virchow was one of the first prominent physicians to emphasize the study of manifestations of disease which were visible only at the cellular level.[1][5] A student of Virchow's, Julius Cohnheim (1839-1884) combined histology techniques with experimental manipulations to study inflammation, making him one of the earliest experimental pathologists.[1] Cohnheim also pioneered the use of the frozen section; a version of this technique is widely employed by modern pathologists to render diagnoses and provide other clinical information intraoperatively.[6]
## Modern experimental pathology
As new research techniques, such as electron microscopy, immunohistochemistry, and molecular biology have expanded the means by which biomedical scientists can study disease, the definition and boundaries of investigative pathology have become less distinct. In the broadest sense, nearly all research which links manifestations of disease to identifiable processes in cells, tissues, or organs can be considered experimental pathology.[7]
# Pathology as a science
Pathology is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the body's means of responding to and repairing injury. Disease processes may be incited or exacerbated by a variety of external and internal influences, including trauma, infection, poisoning, loss of blood flow, autoimmunity, inherited or acquired genetic damage, or errors of development. One common theme in pathology is the way in which the body's responses to injury, while evolved to protect health, can also contribute in some ways to disease processes.[8] Elucidation of general principles underlying pathologic processes, such as cellular adaptation to injury, cell death, inflammation, tissue repair, and neoplasia, creates a conceptual framework with which to analyze and understand specific human diseases.
## Adaptation to injury
Cells and tissues may respond to injury and stress by specific mechanisms, which may vary according to the cell types and nature of the injury. In the short term, cells may activate specific genetic programs to protect their vital proteins and organelles from heat shock or hypoxia, and may activate DNA repair pathways to repair damage to chromosomes from radiation or chemicals. Hyperplasia is a long-term adaptive response of cell division and multiplication, which can increase the ability of a tissue to compensate for an injury. For example, repeated irritation to the skin can cause a protective thickening due to hyperplasia of the epidermis. Hypertrophy is an increase in the size of cells in a tissue in response to stress, an example being hypertrophy of muscle cells in the heart in response to increased resistance to blood flow as a result of narrowing of the heart's outflow valve. Metaplasia occurs when repeated damage to the cellular lining of an organ triggers its replacement by a different cell type.[8]
## Cell death
Necrosis is the irreversible destruction of cells as a result of severe injury in a setting where the cell is unable to activate the needed metabolic pathways for survival or orderly degeneration. This is often due to external pathologic factors, such as toxins or loss of oxygen supply. Milder stresses may lead to a process called reversible cell injury, which mimics the cell swelling and vacuolization seen early in the necrotic process, but in which the cell is able to adapt and survive. In necrosis, the components of degenerating cells leak out, potentially contributing to inflammation and further damage. Apoptosis, in contrast, is a regulated, orderly degeneration of the cell which occurs in the settings of both injury and normal physiological processes.[8]
## Inflammation
Inflammation is a particularly important and complex reaction to tissue injury, and is particularly important in fighting infection. Acute inflammation is generally a non-specific response triggered by the injured tissue cells themselves, as well as specialized cells of the innate immune system and previously developed adaptive immune mechanisms. A localized acute inflammatory response triggers vascular changes in the injured area, recruits pathogen-fighting neutrophils, and begins the process of developing a new adaptive immune response. Chronic inflammation occurs when the acute response fails to entirely clear the inciting factor. While chronic inflammation can lay a positive role in containing a continuing infectious hazard, it can also lead to progressive tissue damage, as well as predisposing (in some cases) to the development of cancer.[8]
## Tissue repair
Tissue repair, as seen in wound healing, is triggered by inflammation. The process may proceed even before the resolution of a precipitating insult, through the formation of granulation tissue. Healing involves the proliferation of connective tissue cells and blood vessel-forming cells as a result of hormonal growth signals. While healing is a critical adaptive response, an aberrent healing response can lead to progressive fibrosis, contractures, or other changes which can compromise function.[8]
## Neoplasia
Neoplasia, or "new growth," is a proliferation of cells which is independent of any physiological process. The most familiar examples of neoplasia are benign tumors and cancers. Neoplasia results from genetic changes which cause cells to activate genetic programs inappropriately. Dysplasia is an early sign of a neoplastic process in a tissue, and is marked by persistence of immature, poorly differentiated cell forms. Interestingly, there are many similarities in the gene pathways activated in cancer cells, and those activated in cells involved in wound healing and inflammation.[8]
# Pathology as a medical specialty
Physicians who practice pathology diagnose and characterize disease in living patients by examining biopsies and other specimens. For example, the vast majority of cancer diagnoses are made or confirmed by a pathologist. Pathologists may also conduct autopsies to investigate causes of death. The medical practice of pathology grew out the tradition of investigative pathology, and many of the academic leaders in pathology today are accomplished in both basic science research and diagnostic practice. However, as with other specialties in medicine, most modern physician-pathologists are employed in full-time practice, and do not perform original research.
Pathology is a unique medical specialty in that pathologists typically do not see patients directly, but rather serve as consultants to other physicians (often referred to as "clinicians" within the pathology community). However, in the United States and in many other countries, pathologists receive the same doctorate training, and undergo the same medical licensure process as other physicians. Pathology is a diverse field, and the organization of subspecialties within pathology vary between nations.
## Anatomical Pathology
Anatomical pathologists diagnose disease and gain other clinically significant information through the examination of tissues and cells. This generally involves gross and microscopic visual examination of tissues, with special stains and immunohistochemistry employed to visualize specific proteins and other substances in and around cells. More recently, anatomical pathologists have begun to employ molecular biology techniques to gain additional clinical information from these same specimens. Anatomic pathologists serve as the definitive diagnosticians for most cancers, as well as numerous other diseases.
- Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.
- Cytopathology is concerned with the microscopic examination of whole, individual cells obtained from smears or fine needle aspirates.
- Molecular pathology refers to the use of nucleic acid-based techniques, such as in-situ hybridization, reverse-transcriptase polymerase chain reaction, and nucleic acid microarrays for specialised diagnostic studies of disease in tissues and cells.
- Autopsies are used to provide definitive evidence of the disease processes contributing to a person's death.
- Forensic pathology receive specialized training in determining the cause of death and other legally relevant information from the bodies of persons who died in a non-medical or potentially criminal circumstances.
## Clinical pathology
Clinical pathology, also known as laboratory medicine, is the medical specialty concerned with diagnosing diseases based on the analysis of body fluids, such as plasma, urine, stool, respiratory or mucosal secretions, inflammatory exudates, and pleural, pericardial, peritoneal, synovial, or cerebrospinal fluid. The practice of clinical pathology is centered around the clinical laboratory. In modern clinical laboratories, many routine studies are largely automated. The clinical pathologist is responsible for overseeing the work of laboratory technicians, performing quality assurance to assure the validity of test results, performing interpretations of more complex studies, and serving as a consultant to clinicians so that the most appropriate studies can be performed for the diagnosis or assessment of an individual patient's condition. In some areas, non-pathologists, such as other physicians or Ph.D.'s may run clinical labs and perform functions within those specific labs which are similar to the role of a board-certified clinical pathologist.
Sub-specialties within clinical pathology include the following:
- Clinical chemistry (A board-certifiable subspecialty, chemical pathology, in the U.S.)
- Hematology and Flow cytometry (Part of a board-certifiable subspecialty, hematology, in the U.S.)
- Blood banking/Transfusion medicine (A board-certifiable subspecialty in the U.S.)
- Medical microbiology (A board-certifiable subspecialty in the U.S.)
- Medical cytogenetics
- Immunology
- Molecular genetic pathology (A board-certifiable subspecialty in the U.S.)
## Dental pathology
In the United States, subspecialty-trained doctors of dental surgery (D.D.S), rather than medical doctors, can be certified by a professional board to practice dental pathology.
# Training of medical pathologists
## Pathology in the United States
In the United States, pathologists are medical doctors (M.D.) or doctors of osteopathic medicine (D.O.), that have completed a four-year undergraduate program, four years of medical school training, and three to four years of postgraduate training in the form of a pathology residency. Training may be within two primary specialties, as recognized by the American Board of Pathology: Anatomic Pathology, and Clinical Pathology, each of which requires separate board certification. Many pathologists seek a broad-based training and become certified in both fields. These skills are complementary in many hospital-based private practice settings, since the day-to-day work of many clinical laboratories only requires the intermittent attention of a physician. Thus, pathologists are able to spend much of their time evaluating anatomic pathology cases, while remaining available to cover any special issues which might arise in the clinical laboratories. Pathologists may pursue specialised fellowship training within one or more sub-specialties of either anatomic or clinical pathology. Some of these sub-specialities permit additional board certification, while others do not.[9]
## Pathology in the United Kingdom
In the UK pathologists are medical doctors registered with the UK General Medical Council. They will have completed an undergraduate medical education which in most countries lasts 4-6 years. The training to become a pathologist is under the oversight of the Royal College of Pathologists. Typically a one year training attachment is followed by an aptitude test. This is followed by further specialist training in surgical pathology, cytopathology, and post mortem pathology. There are two examinations run by the Royal College of Pathologists termed Part 1 and Part 2. The Part 2 examination is designed to test competence to work as an independent practitioner in pathology and is typically taken after 5 years specialist training. All post-graduate medical training and education in the UK is overseen by the Postgraduate Medical Education and Training Board. It is possible to take a specialist part 2 examination in paediatric pathology or neuropathology. It is possible to take a special diploma in dermatopathology or cytopathology, recognising additional specialist training and expertise.
# Non-human pathology
Veterinary pathologists are veterinary practitioners who specialise in the diagnosis and characterization of veterinary diseases through the examination of animal tissue and body fluids. Veterinary pathologists are veterinarians with advanced training (board certification or Ph.D.) in either diagnostic pathology or research into the biological processes underlying disease (pathobiology). Diagnostic veterinary pathologists are further subcategorized as either anatomical pathologists or clinical pathologists. Clinical pathologists examine specimens such as blood, excretions or biopsy material to diagnose disease in living animals. Anatomical pathologists utilize post mortem examinations of dead animals to arrive at a diagnosis. Post mortem examinations entail a necropsy (an animal autopsy), histopathologic (microscopic) study of tissue specimens collected at the necropsy and sometimes specialized studies (radiographic, toxicologic, etc.)
Plant pathologists are specialized scientists who investigate the causes of diseases in plants. | https://www.wikidoc.org/index.php/Pathologist | |
2e35e9e6326a743b483c7eff351dd030964918e2 | wikidoc | Patiromer | Patiromer
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# Overview
Patiromer is a potassium binder that is FDA approved for the treatment of patients with hyperkalemia. Common adverse reactions include constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence (≥2%).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
Patiromer is indicated for the treatment of hyperkalemia.
Limitation of Use: Patiromer should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Administer Patiromer at least 3 hours before or 3 hours after other oral medications.
Administer Patiromer with food. Do not heat Patiromer (e.g., microwave) or add to heated foods or liquids. Do not take Patiromer in its dry form.
- Recommended Dosing and Titration
The recommended starting dose of Patiromer is 8.4 grams once daily. Monitor serum potassium and adjust the dose of Patiromer based on the serum potassium level and the desired target range. The dose may be increased or decreased, as necessary, to reach the desired serum potassium concentration, up to a maximum dose of 25.2 grams once daily. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 grams.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Patiromer in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Patiromer in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
Safety and efficacy in pediatric patients have not been established.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Patiromer in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Patiromer in pediatric patients.
# Contraindications
Patiromer is contraindicated in patients with a history of a hypersensitivity reaction to Patiromer or any of its components
# Warnings
- Worsening of Gastrointestinal Motility
Avoid use of Patiromer in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Patiromer may be ineffective and may worsen gastrointestinal conditions.
Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in the clinical studies.
- Hypomagnesemia
Patiromer binds to magnesium in the colon, which can lead to hypomagnesemia. In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3% of patients treated with Patiromer. Monitor serum magnesium. Consider magnesium supplementation in patients who develop low serum magnesium levels on Patiromer.
# Adverse Reactions
## Clinical Trials Experience
The following adverse reaction is discussed in greater detail elsewhere in the label:
- Hypomagnesemia
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Patiromer cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
In the safety and efficacy clinical trials, 666 adult patients received at least one dose of Patiromer, including 219 exposed for at least 6 months and 149 exposed for at least one year.
Table 1 provides a summary of the most common adverse reactions (occurring in ≥ 2% of patients) in patients treated with Patiromer in these clinical trials. Most adverse reactions were mild to moderate. Constipation generally resolved during the course of treatment.
- Table 1: Adverse Reactions Reported in ≥ 2% of Patients
Veltassa: Patiromer's Brand name
During the clinical studies, the most commonly reported adverse reactions leading to discontinuation of Patiromer were gastrointestinal adverse reactions (2.7%), including vomiting (0.8%), diarrhea (0.6%), constipation (0.5%) and flatulence (0.5%).
Mild to moderate hypersensitivity reactions were reported in 0.3% of patients treated with Patiromer in clinical trials. Reactions have included edema of the lips.
- Laboratory Abnormalities
- Approximately 4.7% of patients in clinical trials developed hypokalemia with a serum potassium value < 3.5 mEq/L.
- Approximately 9% of patients in clinical trials developed hypomagnesemia with a serum magnesium value < 1.4 mg/dL.
## Postmarketing Experience
There is limited information regarding Patiromer Postmarketing Experience in the drug label.
# Drug Interactions
In clinical studies, Patiromer decreased systemic exposure of some coadministered oral medications. Binding of Patiromer to other oral medications could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time Patiromer is administered. Administer other oral medications at least 3 hours before or 3 hours after Patiromer.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Patiromer is not absorbed systemically following oral administration and maternal use is not expected to result in fetal risk.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Patiromer in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Patiromer during labor and delivery.
### Nursing Mothers
Patiromer is not absorbed systemically by the mother, so breastfeeding is not expected to result in risk to the infant.
### Pediatric Use
Safety and efficacy in pediatric patients have not been established.
### Geriatic Use
Of the 666 patients treated with Patiromer in clinical studies, 59.8% were age 65 and over, and 19.8% were age 75 and over. No overall differences in effectiveness were observed between these patients and younger patients. Patients age 65 and older reported more gastrointestinal adverse reactions than younger patients.
### Gender
There is no FDA guidance on the use of Patiromer with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Patiromer with respect to specific racial populations.
### Renal Impairment
Of the 666 patients treated with Patiromer in clinical studies, 93% had chronic kidney disease (CKD). No special dosing adjustments are needed for patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Patiromer in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Patiromer in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Patiromer in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Preparation of Patiromer
Prepare each dose immediately prior to administration.
Measure 1/3 cup of water. Pour half of the water into a glass, then add Patiromer and stir. Add the remaining half of the water and stir thoroughly. The powder will not dissolve and the mixture will look cloudy. Add more water to the mixture as needed for desired consistency.
Drink the mixture immediately. If powder remains in the glass after drinking, add more water, stir and drink immediately. Repeat as needed to ensure the entire dose is administered.
### Monitoring
There is limited information regarding Patiromer Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Patiromer and IV administrations.
# Overdosage
Doses of Patiromer in excess of 50.4 grams per day have not been tested. Excessive doses of Patiromer may result in hypokalemia. Restore serum potassium if hypokalemia occurs.
# Pharmacology
## Mechanism of Action
Patiromer is a non-absorbed, cation exchange polymer that contains a calcium-sorbitol counterion.
Patiromer increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels.
## Structure
Patiromer is a powder for suspension in water for oral administration. The active ingredient is patiromer sorbitex calcium which consists of the active moiety, patiromer, a non-absorbed potassium-binding polymer, and a calcium-sorbitol counterion. Each gram of patiromer is equivalent to a nominal amount of 2 grams of patiromer sorbitex calcium.
The chemical name for patiromer sorbitex calcium is cross-linked polymer of calcium 2-fluoroprop-2-enoate with diethenylbenzene and octa-1,7-diene, combination with D-glucitol.
Patiromer sorbitex calcium is an amorphous, free-flowing powder that is composed of individual spherical beads. Patiromer sorbitex calcium is insoluble in solvents such as water, 0.1 M HCl, n-heptane and methanol. The chemical structure of patiromer sorbitex calcium is presented in Figure 1.
- Figure 1: Chemical Structure of Patiromer Sorbitex Calcium
Each packet of this drug contains 8.4 grams, 16.8 grams or 25.2 grams of patiromer, the active moiety. The inactive ingredient is xanthan gum.
## Pharmacodynamics
In a Phase 1 study in healthy adult subjects (6 to 8 subjects per group), Patiromer (0 grams to 50.4 grams per day) administered three times a day for 8 days caused a dose-dependent increase in fecal potassium excretion. A corresponding dose-dependent decrease in urinary potassium excretion with no change in serum potassium were also observed. Compared to placebo, Patiromer doses of 25.2 and 50.4 grams per day significantly decreased mean daily urinary potassium excretion.
In a Phase 1, open-label, multiple-dose crossover study in 12 healthy subjects, 25.2 grams of patiromer per day was administered orally as a once daily, twice daily or thrice daily regimen for 6 days in a randomly assigned order. A significant increase in mean daily fecal potassium excretion and concomitant decrease in mean daily urinary potassium excretion were observed during the treatment periods for all three dosing regimens. The mean increase in fecal potassium excretion ranged from 1283 to 1550 mg/day, and the mean decrease in urinary potassium excretion ranged from 1438 to 1534 mg/day across the three dosing regimens. No significant differences were observed among the dosing regimens with respect to mean daily fecal potassium and urinary potassium excretion. This was true for the overall comparison among the three dosing regimens, as well as for the pairwise comparisons.
In an open-label, uncontrolled study, 25 patients with hyperkalemia (mean baseline serum potassium of 5.9 mEq/L) and chronic kidney disease were given a controlled potassium diet for 3 days, followed by 16.8 grams patiromer daily (as divided doses) for 2 days while the controlled diet was continued. A statistically significant reduction in serum potassium (-0.2 mEq/L) was observed at 7 hours after the first dose. Serum potassium levels continued to decline during the 48-hour treatment period (-0.8 mEq/L at 48 hours after the first dose). Potassium levels remained stable for 24 hours after the last dose, then rose during the 4-day observation period following discontinuation of Patiromer.
## Pharmacokinetics
In radiolabeled ADME studies in rats and dogs, patiromer was not systemically absorbed and was excreted in the feces. Quantitative whole-body autoradiography analysis in rats demonstrated that radioactivity was limited to the gastrointestinal tract, with no detectable level of radioactivity in any other tissues or organs.
- Drug Interactions
Twenty-eight (28) drugs were tested to determine the potential for interaction with Patiromer.
Fourteen (14) drugs tested did not show an in vitro interaction with Patiromer (acetylsalicylic acid, allopurinol, amoxicillin, apixaban, atorvastatin, cephalexin, digoxin, glipizide, lisinopril, phenytoin, riboflavin, rivaroxaban, spironolactone and valsartan).
Twelve (12) of the 14 drugs that showed an in vitro interaction were subsequently tested in vivo. These studies in healthy volunteers showed that Patiromer did not alter the systemic exposure of amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil or warfarin when coadministered with Patiromer. Patiromer decreased the systemic exposure of coadministered ciprofloxacin, levothyroxine and metformin. However, there was no interaction when Patiromer and these drugs were taken 3 hours apart (Figure 2).
- Figure 2: Effects of Patiromer on the Pharmacokinetic Exposures of Other Orally Administered Medications with No Dosing Separation and with a 3-Hour Separation
## Nonclinical Toxicology
Patiromer was not genotoxic in the reverse mutation test (Ames assay), chromosome aberration or rat micronucleus assays.
Carcinogenicity studies have not been performed.
Patiromer did not impair the fertility in male or female rats at doses up to 10-fold the maximum recommended human dose (MRHD).
# Clinical Studies
- Two-Part, Randomized Withdrawal Study
The efficacy of Patiromer was demonstrated in a two-part, single-blind randomized withdrawal study that evaluated Patiromer in hyperkalemic patients with CKD on stable doses of at least one renin-angiotensin-aldosterone system inhibitor (i.e., angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or aldosterone antagonist).
In Part A, 243 patients were treated with Patiromer for 4 weeks. Patients with a baseline serum potassium of 5.1 mEq/L to < 5.5 mEq/L received a starting Patiromer dose of 8.4 grams patiromer per day (as a divided dose) and patients with a baseline serum potassium of 5.5 mEq/L to < 6.5 mEq/L received a starting Patiromer dose of 16.8 grams patiromer per day (as a divided dose). The dose of Patiromer was titrated, as needed, based on the serum potassium level, assessed starting on Day 3 and then at weekly visits (Weeks 1, 2 and 3) to the end of the 4-week treatment period, with the aim of maintaining serum potassium in the target range (3.8 mEq/L to < 5.1 mEq/L).
The mean age of patients was 64 years, 58% of patients were men, and 98% were Caucasian. Approximately 97% of patients had hypertension, 57% had type 2 diabetes, and 42% had heart failure.
Results for the Part A primary endpoint, the change in serum potassium from Baseline to Week 4, are summarized in Table 2. Mean serum potassium over time for the intent-to-treat population is displayed in Figure 3. For the Part A secondary endpoint, 76% (95% confidence interval : 70%, 81%) of patients had a serum potassium in the target range of 3.8 mEq/L to < 5.1 mEq/L at Week 4. The mean daily doses of Patiromer were 13 grams and 21 grams in patients with serum potassium of 5.1 to < 5.5 mEq/L and 5.5 to < 6.5 mEq/L, respectively.
- Table 2: Patiromer Treatment Phase (Part A): Primary Endpoint
- Figure 3: Estimated Mean (95% CI) of Central Serum Potassium (mEq/L) Over Time
In Part B, 107 patients with a Part A baseline serum potassium of 5.5 mEq/L to < 6.5 mEq/L and whose serum potassium was in the target range (3.8 mEq/L to < 5.1 mEq/L) at Part A Week 4 and still receiving RAAS inhibitor medication were randomized to continue Patiromer or to receive placebo to evaluate the effect of withdrawing Patiromer on serum potassium. In patients randomized to Patiromer, the mean daily dose was 21 grams at the start of Part B and during Part B.
The Part B primary endpoint was the change in serum potassium from Part B baseline to the earliest visit at which the patient's serum potassium was first outside of the range of 3.8 to < 5.5 mEq/L, or to Part B Week 4 if the patient's serum potassium remained in the range. In Part B, serum potassium rose by 0.72 mEq/L in patients who were switched to placebo, versus no change in patients who remained on Patiromer. Results are summarized in Table 3.
- Table 3: Randomized, Placebo-Controlled Withdrawal Phase (Part B): Primary Endpoint
Veltassa: Patiromer's Brand name
More placebo patients (91%; 95% CI: 83%, 99%) developed a serum potassium ≥ 5.1 mEq/L at any time during Part B than Patiromer patients (43%; 95% CI: 30%, 56%), p < 0.001. More placebo patients (60%; 95% CI: 47%, 74%) developed a serum potassium ≥ 5.5 mEq/L at any time during Part B than Patiromer patients (15%; 95% CI: 6%, 24%), p < 0.001.
- One-Year Study
The effect of treatment with Patiromer for up to 52 weeks was evaluated in an open-label study of 304 hyperkalemic patients with CKD and type 2 diabetes mellitus on RAAS inhibitor therapy. Figure 4 shows that the treatment effect on serum potassium was maintained during continued therapy. In patients with a baseline serum potassium of > 5.0 to 5.5 mEq/L who received an initial dose of 8.4 grams patiromer per day (as a divided dose), the mean daily dose was 14 grams; in those with a baseline serum potassium of > 5.5 to < 6.0 mEq/L who received an initial dose of 16.8 grams patiromer per day (as a divided dose), the mean daily dose was 20 grams during the entire study.
- Figure 4: Mean (95% CI) Serum Potassium over Time
# How Supplied
Patiromer is supplied as an off-white to light-brown powder for oral suspension formulated with xanthan gum. Patiromer is packaged in single-use packets containing 8.4 grams, 16.8 grams or 25.2 grams patiromer as follows:
Veltassa: Patiromer's Brand name
## Storage
Patiromer should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F).
If stored at room temperature (25°C ± 2°C ), Patiromer must be used within 3 months of being taken out of the refrigerator. For either storage condition, do not use Patiromer after the expiration date printed on the packet.
Avoid exposure to excessive heat above 40°C (104°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Drug Interactions
Advise patients who are taking other oral medication to separate the dosing of Patiromer by at least 3 hours (before or after).
- Dosing Recommendations
Inform patients to take Patiromer as directed with food and adhere to their prescribed diets.
Inform patients that Patiromer should not be heated (e.g., microwaved) or added to heated foods or liquids and should not be taken in its dry form.
# Precautions with Alcohol
Alcohol-Patiromer interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
Veltassa®
# Look-Alike Drug Names
There is limited information regarding Patiromer Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Patiromer
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino [2]
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# Overview
Patiromer is a potassium binder that is FDA approved for the treatment of patients with hyperkalemia. Common adverse reactions include constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence (≥2%).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
Patiromer is indicated for the treatment of hyperkalemia.
Limitation of Use: Patiromer should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Administer Patiromer at least 3 hours before or 3 hours after other oral medications.
Administer Patiromer with food. Do not heat Patiromer (e.g., microwave) or add to heated foods or liquids. Do not take Patiromer in its dry form.
- Recommended Dosing and Titration
The recommended starting dose of Patiromer is 8.4 grams once daily. Monitor serum potassium and adjust the dose of Patiromer based on the serum potassium level and the desired target range. The dose may be increased or decreased, as necessary, to reach the desired serum potassium concentration, up to a maximum dose of 25.2 grams once daily. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 grams.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Patiromer in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Patiromer in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
Safety and efficacy in pediatric patients have not been established.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Patiromer in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Patiromer in pediatric patients.
# Contraindications
Patiromer is contraindicated in patients with a history of a hypersensitivity reaction to Patiromer or any of its components
# Warnings
- Worsening of Gastrointestinal Motility
Avoid use of Patiromer in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Patiromer may be ineffective and may worsen gastrointestinal conditions.
Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in the clinical studies.
- Hypomagnesemia
Patiromer binds to magnesium in the colon, which can lead to hypomagnesemia. In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3% of patients treated with Patiromer. Monitor serum magnesium. Consider magnesium supplementation in patients who develop low serum magnesium levels on Patiromer.
# Adverse Reactions
## Clinical Trials Experience
The following adverse reaction is discussed in greater detail elsewhere in the label:
- Hypomagnesemia
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Patiromer cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
In the safety and efficacy clinical trials, 666 adult patients received at least one dose of Patiromer, including 219 exposed for at least 6 months and 149 exposed for at least one year.
Table 1 provides a summary of the most common adverse reactions (occurring in ≥ 2% of patients) in patients treated with Patiromer in these clinical trials. Most adverse reactions were mild to moderate. Constipation generally resolved during the course of treatment.
- Table 1: Adverse Reactions Reported in ≥ 2% of Patients
Veltassa: Patiromer's Brand name
During the clinical studies, the most commonly reported adverse reactions leading to discontinuation of Patiromer were gastrointestinal adverse reactions (2.7%), including vomiting (0.8%), diarrhea (0.6%), constipation (0.5%) and flatulence (0.5%).
Mild to moderate hypersensitivity reactions were reported in 0.3% of patients treated with Patiromer in clinical trials. Reactions have included edema of the lips.
- Laboratory Abnormalities
- Approximately 4.7% of patients in clinical trials developed hypokalemia with a serum potassium value < 3.5 mEq/L.
- Approximately 9% of patients in clinical trials developed hypomagnesemia with a serum magnesium value < 1.4 mg/dL.
## Postmarketing Experience
There is limited information regarding Patiromer Postmarketing Experience in the drug label.
# Drug Interactions
In clinical studies, Patiromer decreased systemic exposure of some coadministered oral medications. Binding of Patiromer to other oral medications could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time Patiromer is administered. Administer other oral medications at least 3 hours before or 3 hours after Patiromer.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Patiromer is not absorbed systemically following oral administration and maternal use is not expected to result in fetal risk.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Patiromer in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Patiromer during labor and delivery.
### Nursing Mothers
Patiromer is not absorbed systemically by the mother, so breastfeeding is not expected to result in risk to the infant.
### Pediatric Use
Safety and efficacy in pediatric patients have not been established.
### Geriatic Use
Of the 666 patients treated with Patiromer in clinical studies, 59.8% were age 65 and over, and 19.8% were age 75 and over. No overall differences in effectiveness were observed between these patients and younger patients. Patients age 65 and older reported more gastrointestinal adverse reactions than younger patients.
### Gender
There is no FDA guidance on the use of Patiromer with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Patiromer with respect to specific racial populations.
### Renal Impairment
Of the 666 patients treated with Patiromer in clinical studies, 93% had chronic kidney disease (CKD). No special dosing adjustments are needed for patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Patiromer in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Patiromer in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Patiromer in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Preparation of Patiromer
Prepare each dose immediately prior to administration.
Measure 1/3 cup of water. Pour half of the water into a glass, then add Patiromer and stir. Add the remaining half of the water and stir thoroughly. The powder will not dissolve and the mixture will look cloudy. Add more water to the mixture as needed for desired consistency.
Drink the mixture immediately. If powder remains in the glass after drinking, add more water, stir and drink immediately. Repeat as needed to ensure the entire dose is administered.
### Monitoring
There is limited information regarding Patiromer Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Patiromer and IV administrations.
# Overdosage
Doses of Patiromer in excess of 50.4 grams per day have not been tested. Excessive doses of Patiromer may result in hypokalemia. Restore serum potassium if hypokalemia occurs.
# Pharmacology
## Mechanism of Action
Patiromer is a non-absorbed, cation exchange polymer that contains a calcium-sorbitol counterion.
Patiromer increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels.
## Structure
Patiromer is a powder for suspension in water for oral administration. The active ingredient is patiromer sorbitex calcium which consists of the active moiety, patiromer, a non-absorbed potassium-binding polymer, and a calcium-sorbitol counterion. Each gram of patiromer is equivalent to a nominal amount of 2 grams of patiromer sorbitex calcium.
The chemical name for patiromer sorbitex calcium is cross-linked polymer of calcium 2-fluoroprop-2-enoate with diethenylbenzene and octa-1,7-diene, combination with D-glucitol.
Patiromer sorbitex calcium is an amorphous, free-flowing powder that is composed of individual spherical beads. Patiromer sorbitex calcium is insoluble in solvents such as water, 0.1 M HCl, n-heptane and methanol. The chemical structure of patiromer sorbitex calcium is presented in Figure 1.
- Figure 1: Chemical Structure of Patiromer Sorbitex Calcium
Each packet of this drug contains 8.4 grams, 16.8 grams or 25.2 grams of patiromer, the active moiety. The inactive ingredient is xanthan gum.
## Pharmacodynamics
In a Phase 1 study in healthy adult subjects (6 to 8 subjects per group), Patiromer (0 grams to 50.4 grams per day) administered three times a day for 8 days caused a dose-dependent increase in fecal potassium excretion. A corresponding dose-dependent decrease in urinary potassium excretion with no change in serum potassium were also observed. Compared to placebo, Patiromer doses of 25.2 and 50.4 grams per day significantly decreased mean daily urinary potassium excretion.
In a Phase 1, open-label, multiple-dose crossover study in 12 healthy subjects, 25.2 grams of patiromer per day was administered orally as a once daily, twice daily or thrice daily regimen for 6 days in a randomly assigned order. A significant increase in mean daily fecal potassium excretion and concomitant decrease in mean daily urinary potassium excretion were observed during the treatment periods for all three dosing regimens. The mean increase in fecal potassium excretion ranged from 1283 to 1550 mg/day, and the mean decrease in urinary potassium excretion ranged from 1438 to 1534 mg/day across the three dosing regimens. No significant differences were observed among the dosing regimens with respect to mean daily fecal potassium and urinary potassium excretion. This was true for the overall comparison among the three dosing regimens, as well as for the pairwise comparisons.
In an open-label, uncontrolled study, 25 patients with hyperkalemia (mean baseline serum potassium of 5.9 mEq/L) and chronic kidney disease were given a controlled potassium diet for 3 days, followed by 16.8 grams patiromer daily (as divided doses) for 2 days while the controlled diet was continued. A statistically significant reduction in serum potassium (-0.2 mEq/L) was observed at 7 hours after the first dose. Serum potassium levels continued to decline during the 48-hour treatment period (-0.8 mEq/L at 48 hours after the first dose). Potassium levels remained stable for 24 hours after the last dose, then rose during the 4-day observation period following discontinuation of Patiromer.
## Pharmacokinetics
In radiolabeled ADME studies in rats and dogs, patiromer was not systemically absorbed and was excreted in the feces. Quantitative whole-body autoradiography analysis in rats demonstrated that radioactivity was limited to the gastrointestinal tract, with no detectable level of radioactivity in any other tissues or organs.
- Drug Interactions
Twenty-eight (28) drugs were tested to determine the potential for interaction with Patiromer.
Fourteen (14) drugs tested did not show an in vitro interaction with Patiromer (acetylsalicylic acid, allopurinol, amoxicillin, apixaban, atorvastatin, cephalexin, digoxin, glipizide, lisinopril, phenytoin, riboflavin, rivaroxaban, spironolactone and valsartan).
Twelve (12) of the 14 drugs that showed an in vitro interaction were subsequently tested in vivo. These studies in healthy volunteers showed that Patiromer did not alter the systemic exposure of amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil or warfarin when coadministered with Patiromer. Patiromer decreased the systemic exposure of coadministered ciprofloxacin, levothyroxine and metformin. However, there was no interaction when Patiromer and these drugs were taken 3 hours apart (Figure 2).
- Figure 2: Effects of Patiromer on the Pharmacokinetic Exposures of Other Orally Administered Medications with No Dosing Separation and with a 3-Hour Separation
## Nonclinical Toxicology
Patiromer was not genotoxic in the reverse mutation test (Ames assay), chromosome aberration or rat micronucleus assays.
Carcinogenicity studies have not been performed.
Patiromer did not impair the fertility in male or female rats at doses up to 10-fold the maximum recommended human dose (MRHD).
# Clinical Studies
- Two-Part, Randomized Withdrawal Study
The efficacy of Patiromer was demonstrated in a two-part, single-blind randomized withdrawal study that evaluated Patiromer in hyperkalemic patients with CKD on stable doses of at least one renin-angiotensin-aldosterone system inhibitor (i.e., angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or aldosterone antagonist).
In Part A, 243 patients were treated with Patiromer for 4 weeks. Patients with a baseline serum potassium of 5.1 mEq/L to < 5.5 mEq/L received a starting Patiromer dose of 8.4 grams patiromer per day (as a divided dose) and patients with a baseline serum potassium of 5.5 mEq/L to < 6.5 mEq/L received a starting Patiromer dose of 16.8 grams patiromer per day (as a divided dose). The dose of Patiromer was titrated, as needed, based on the serum potassium level, assessed starting on Day 3 and then at weekly visits (Weeks 1, 2 and 3) to the end of the 4-week treatment period, with the aim of maintaining serum potassium in the target range (3.8 mEq/L to < 5.1 mEq/L).
The mean age of patients was 64 years, 58% of patients were men, and 98% were Caucasian. Approximately 97% of patients had hypertension, 57% had type 2 diabetes, and 42% had heart failure.
Results for the Part A primary endpoint, the change in serum potassium from Baseline to Week 4, are summarized in Table 2. Mean serum potassium over time for the intent-to-treat population is displayed in Figure 3. For the Part A secondary endpoint, 76% (95% confidence interval [CI]: 70%, 81%) of patients had a serum potassium in the target range of 3.8 mEq/L to < 5.1 mEq/L at Week 4. The mean daily doses of Patiromer were 13 grams and 21 grams in patients with serum potassium of 5.1 to < 5.5 mEq/L and 5.5 to < 6.5 mEq/L, respectively.
- Table 2: Patiromer Treatment Phase (Part A): Primary Endpoint
- Figure 3: Estimated Mean (95% CI) of Central Serum Potassium (mEq/L) Over Time
In Part B, 107 patients with a Part A baseline serum potassium of 5.5 mEq/L to < 6.5 mEq/L and whose serum potassium was in the target range (3.8 mEq/L to < 5.1 mEq/L) at Part A Week 4 and still receiving RAAS inhibitor medication were randomized to continue Patiromer or to receive placebo to evaluate the effect of withdrawing Patiromer on serum potassium. In patients randomized to Patiromer, the mean daily dose was 21 grams at the start of Part B and during Part B.
The Part B primary endpoint was the change in serum potassium from Part B baseline to the earliest visit at which the patient's serum potassium was first outside of the range of 3.8 to < 5.5 mEq/L, or to Part B Week 4 if the patient's serum potassium remained in the range. In Part B, serum potassium rose by 0.72 mEq/L in patients who were switched to placebo, versus no change in patients who remained on Patiromer. Results are summarized in Table 3.
- Table 3: Randomized, Placebo-Controlled Withdrawal Phase (Part B): Primary Endpoint
Veltassa: Patiromer's Brand name
More placebo patients (91%; 95% CI: 83%, 99%) developed a serum potassium ≥ 5.1 mEq/L at any time during Part B than Patiromer patients (43%; 95% CI: 30%, 56%), p < 0.001. More placebo patients (60%; 95% CI: 47%, 74%) developed a serum potassium ≥ 5.5 mEq/L at any time during Part B than Patiromer patients (15%; 95% CI: 6%, 24%), p < 0.001.
- One-Year Study
The effect of treatment with Patiromer for up to 52 weeks was evaluated in an open-label study of 304 hyperkalemic patients with CKD and type 2 diabetes mellitus on RAAS inhibitor therapy. Figure 4 shows that the treatment effect on serum potassium was maintained during continued therapy. In patients with a baseline serum potassium of > 5.0 to 5.5 mEq/L who received an initial dose of 8.4 grams patiromer per day (as a divided dose), the mean daily dose was 14 grams; in those with a baseline serum potassium of > 5.5 to < 6.0 mEq/L who received an initial dose of 16.8 grams patiromer per day (as a divided dose), the mean daily dose was 20 grams during the entire study.
- Figure 4: Mean (95% CI) Serum Potassium over Time
# How Supplied
Patiromer is supplied as an off-white to light-brown powder for oral suspension formulated with xanthan gum. Patiromer is packaged in single-use packets containing 8.4 grams, 16.8 grams or 25.2 grams patiromer as follows:
Veltassa: Patiromer's Brand name
## Storage
Patiromer should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F).
If stored at room temperature (25°C ± 2°C [77°F ± 4°F]), Patiromer must be used within 3 months of being taken out of the refrigerator. For either storage condition, do not use Patiromer after the expiration date printed on the packet.
Avoid exposure to excessive heat above 40°C (104°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Drug Interactions
Advise patients who are taking other oral medication to separate the dosing of Patiromer by at least 3 hours (before or after).
- Dosing Recommendations
Inform patients to take Patiromer as directed with food and adhere to their prescribed diets.
Inform patients that Patiromer should not be heated (e.g., microwaved) or added to heated foods or liquids and should not be taken in its dry form.
# Precautions with Alcohol
Alcohol-Patiromer interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
Veltassa®
# Look-Alike Drug Names
There is limited information regarding Patiromer Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Patiromer | |
a74293b60d94fd7be203dc7c25ee89dc7557df57 | wikidoc | Paul Berg | Paul Berg
Paul Berg (born June 30, 1926 in Brooklyn, New York, U.S.) is an American biochemist and professor emeritus at Stanford University. He graduated from Abraham Lincoln High School in 1943, received his B.S. in biochemistry from Penn State University in 1948 and Ph.D. in biochemistry from Case Western Reserve University in 1952. In 1980 he shared half of the Nobel Prize for Chemistry with the team of Walter Gilbert and Frederick Sanger. All three were recognized for their important contributions to basic research in nucleic acids. His studies as a postgraduate involved the use of radioisotope tracers in intermediary metabolism. This resulted in the understanding of how foodstuffs are converted to cellular materials, through the use of isotopic carbons or heavy nitrogen atoms. Paul Berg's doctorate paper is now known as the conversion of formic acid, formaldehyde and methanol to fully reduced states of methyl groups in methionine. He was also one of the first to demonstrate that folic Acid and B12 cofactors had roles in the processes mentioned.
Paul's new research has ventured from metabolic biochemistry, and as a professor in Stanford University he now researches Molecular Biology and Recombinant DNA. His main goal now, is to target exogenous genes to specific loci in the genome at high frequencies. Other studies, involving the HIV-1 virus, are being conducted by his research team. The HIV-1 virus induces an immunodeficiency disease that infects T-helper cells.
Prof. Berg is a member of the Board of Sponsors of The Bulletin of the Atomic Scientists . He was also an organizer of the Asilomar conference on recombinant DNA in 1975. The previous year, Berg and other scientists had called for a voluntary moratorium on certain recombinant DNA research until they could evaluate the risks. That influential conference did evaluate the potential hazards and set guidelines for biotechnology research. It can be seen as an early application of the precautionary principle.
Berg was also awarded the National Medal of Science in 1983, by Ronald Reagan. | Paul Berg
Paul Berg (born June 30, 1926 in Brooklyn, New York, U.S.) is an American biochemist and professor emeritus at Stanford University. He graduated from Abraham Lincoln High School in 1943, received his B.S. in biochemistry from Penn State University in 1948 and Ph.D. in biochemistry from Case Western Reserve University in 1952. In 1980 he shared half of the Nobel Prize for Chemistry with the team of Walter Gilbert and Frederick Sanger. All three were recognized for their important contributions to basic research in nucleic acids. His studies as a postgraduate involved the use of radioisotope tracers in intermediary metabolism. This resulted in the understanding of how foodstuffs are converted to cellular materials, through the use of isotopic carbons or heavy nitrogen atoms. Paul Berg's doctorate paper is now known as the conversion of formic acid, formaldehyde and methanol to fully reduced states of methyl groups in methionine. He was also one of the first to demonstrate that folic Acid and B12 cofactors had roles in the processes mentioned.
Paul's new research has ventured from metabolic biochemistry, and as a professor in Stanford University he now researches Molecular Biology and Recombinant DNA. His main goal now, is to target exogenous genes to specific loci in the genome at high frequencies. Other studies, involving the HIV-1 virus, are being conducted by his research team. The HIV-1 virus induces an immunodeficiency disease that infects T-helper cells.
Prof. Berg is a member of the Board of Sponsors of The Bulletin of the Atomic Scientists [1]. He was also an organizer of the Asilomar conference on recombinant DNA in 1975. The previous year, Berg and other scientists had called for a voluntary moratorium on certain recombinant DNA research until they could evaluate the risks. That influential conference did evaluate the potential hazards and set guidelines for biotechnology research. It can be seen as an early application of the precautionary principle.
Berg was also awarded the National Medal of Science in 1983, by Ronald Reagan.
# External links
- Paul Berg narrating "Protein Synthesis: An Epic on the Cellular Level" at Google Video
- Curriculum vitae from the Nobel Prize website
- 2001 article about Berg from a Stanford University website
- [2] from the Nobel Prize website
- [3] from the Nobel Prize website
- Carl Sagan Prize for Science Popularization award recipient, Wonderfest 2006.
Template:Nobel Prize in Chemistry Laureates 1976-2000
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ca:Paul Berg
de:Paul Berg
gd:Paul Berg
id:Paul Berg
he:פול ברג
fi:Paul Berg
sv:Paul Berg
Template:Jb1
Template:WS
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Paul_Berg | |
856c7902da18bc7b56325da7e998ba79c4bfaa41 | wikidoc | Pax genes | Pax genes
Paired box (Pax) genes are a family of tissue specific transcription factors containing a PAIRED domain and usually a partial or complete homeodomain. An octapeptide may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.
# Groups
Within the mammalian family, there are four well defined groups of Pax genes.
- Pax group 1 (Pax 1 and 9),
- Pax group 2 (Pax 2, 5 and 8),
- Pax group 3 (Pax 3 and 7) and
- Pax group 4 (Pax 4 and 6).
Orthologous genes exist throughout the Metazoa, including extensive study of the ectopic expression in Drosophila using murine Pax6.
# Members
- PAX1 has been identified in mice with the development of vertebrate and embryo segmentation, and some evidence this is also true in humans. It transcribes a 440 amino acid protein from 4 exons and 1,323bps in humans.
- PAX2 has been identified with kidney and optic nerve development. It transcribes a 417 amino acid protein from 11 exons and 4,261 bps in humans. Mutation of PAX2 in humans has been associated with renal-coloboma syndrome as well as oligomeganephronia.
- PAX3 has been identified with ear, eye and facial development. It transcribes a 479 amino acid protein in humans. Mutations in it can cause Waardenburg syndrome.
- PAX4 has been identified with pancreatic islet beta cells. It transcribes a 350 amino acid protein from 9 exons and 2,010 bps in humans.
- PAX5 has been identified with neural and spermatogenesis development and b-cell differentiation. It transcribes a 391 amino acid protein from 10 exons and 3,644bps in humans.
- PAX6 is the most researched and appears throughout the literature as a "master control" gene for the development of eyes and sensory organs, certain neural and epidermal tissues as well as other homologous structures, usually derived from ectodermal tissues.
- PAX7 has been possibly associated with myogenesis. It transcribes a protein of 520 amino acids from 8 exons and 2,260bps in humans. PAX7 is required for the developmental specification of satellite cells in skeletal muscle.
- PAX8 has been associated with thyroid specific expression. It transcribes a protein of 451 amino acids from 11 exons and 2,526bps in humans.
- PAX9 has found to be associated with a number of organ and other skeletal developments, particularly teeth. It transcribes a protein of 341 amino acids from 4 exons and 1,644bps in humans. | Pax genes
Paired box (Pax) genes are a family of tissue specific transcription factors containing a PAIRED domain and usually a partial or complete homeodomain. An octapeptide may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.
# Groups
Within the mammalian family, there are four well defined groups of Pax genes.
- Pax group 1 (Pax 1 and 9),
- Pax group 2 (Pax 2, 5 and 8),
- Pax group 3 (Pax 3 and 7) and
- Pax group 4 (Pax 4 and 6).
Orthologous genes exist throughout the Metazoa, including extensive study of the ectopic expression in Drosophila using murine Pax6.
# Members
- PAX1 has been identified in mice with the development of vertebrate and embryo segmentation, and some evidence this is also true in humans. It transcribes a 440 amino acid protein from 4 exons and 1,323bps in humans.
- PAX2 has been identified with kidney and optic nerve development. It transcribes a 417 amino acid protein from 11 exons and 4,261 bps in humans. Mutation of PAX2 in humans has been associated with renal-coloboma syndrome as well as oligomeganephronia.[1]
- PAX3 has been identified with ear, eye and facial development. It transcribes a 479 amino acid protein in humans. Mutations in it can cause Waardenburg syndrome.
- PAX4 has been identified with pancreatic islet beta cells. It transcribes a 350 amino acid protein from 9 exons and 2,010 bps in humans.
- PAX5 has been identified with neural and spermatogenesis development and b-cell differentiation. It transcribes a 391 amino acid protein from 10 exons and 3,644bps in humans.
- PAX6 is the most researched and appears throughout the literature as a "master control" gene for the development of eyes and sensory organs, certain neural and epidermal tissues as well as other homologous structures, usually derived from ectodermal tissues.
- PAX7 has been possibly associated with myogenesis. It transcribes a protein of 520 amino acids from 8 exons and 2,260bps in humans. PAX7 is required for the developmental specification of satellite cells in skeletal muscle.
- PAX8 has been associated with thyroid specific expression. It transcribes a protein of 451 amino acids from 11 exons and 2,526bps in humans.
- PAX9 has found to be associated with a number of organ and other skeletal developments, particularly teeth. It transcribes a protein of 341 amino acids from 4 exons and 1,644bps in humans. | https://www.wikidoc.org/index.php/Pax_genes | |
834ceebdb41946f2fcfe8efb4a3ffd34ffe8dd56 | wikidoc | Paxilline | Paxilline
Paxilline is a potassium channel blocker. Paxilline is a toxic, tremorgenic indole alkaloid produced by Penicillium paxilli.
Disambiguation:
Paxilline, a mycotoxin of penicillium origin, should not be confused with
Paxillin, a signal transducing adaptor protein involved in cell migration (MESH, NCBI).
# Sources and references
- ↑ Paxilline product page from Fermentek | Paxilline
Paxilline is a potassium channel blocker. Paxilline is a toxic, tremorgenic indole alkaloid produced by Penicillium paxilli.
Disambiguation:
Paxilline, a mycotoxin of penicillium origin, should not be confused with
Paxillin, a signal transducing adaptor protein involved in cell migration (MESH, NCBI).[1]
# Sources and references
- ↑ Paxilline product page from Fermentek
Template:Potassium channel blockers
Template:Organic-compound-stub | https://www.wikidoc.org/index.php/Paxilline | |
549d28cb0ba529a642b0ddea79234c6ac322b6ac | wikidoc | Pemphigus | Pemphigus
# Overview
Pemphigus is an autoimmune disorder that causes blistering and raw sores on skin and mucous membranes. As with other autoimmune disorders, it is caused when the body's defenses mistake its own tissues as foreign, and attack the cells. This particular autoimmune reaction is sometimes associated with the use of Penicillamine. Pemphigus is derived from the Greek pemphix, meaning bubble or blister.
# Types
There are three types of pemphigus which vary in severity: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus.
- The most common form of the disorder is pemphigus vulgaris (ICD-10 L10.0). It occurs when antibodies attack Desmoglein 3, a protein that keeps cells bound together. Thus, cells simply fall apart, causing skin to slough off. Although pemphigus vulgaris may occur at any age, it is quite rare in children, and most common in the middle aged and elderly. Sores often originate in the mouth, making eating difficult and uncomfortable. Pemphigus vulgaris often affects people between the ages of 40-60, and mainly of Jewish, Middle Eastern, or Mediterranean descent. Some patients are associated with myasthenia gravis, but it's unusual.
- Foliaceus is the least severe of the three varieties. Desmoglein 1, the protein that is destroyed by the body's immune system is only found in the top dry layer of the skin, so mouth sores do not occur. Pemphigus foliaceus is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. It is not as painful as pemphigus vulgaris, and is often mis-diagnosed as dermatitis or eczema.
- The least common and most severe type of pemphigus is the neoplastic variety, also known as paraneoplastic pemphigus. This disorder is usually found in conjunction with an already-existing malignancy. Very painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves Bronchiolitis obliterans, a fatal destruction of alveoli in lung tissue. A diagnosis of neoplastic pemphigus may prompt a search for an existing tumor. Sometimes, the tumor is not malignant. In these cases, tumor removal may lead to a remission of the pemphigus. However, any decline in pulmonary function is generally irreversible. With Intravenous Immunoglobulin (IVIG) treatment and aggressive chemotherapy for the underlying lympoma, there are few known survivors of Paraneoplastic Pemphigus with pulmonary involvement (contact information in External Links below).
# Diagnosis
Diagnosis relies on microscopic examination of skin lesion samples. A biopsy of a suspected lesion is taken: a sample of the blistered skin is removed and examined under the microscope to determine if the cells are separated in the manner characteristic of pemphigus. Unlike in the related pemphigoid, pemphigus manifests as intra-epithelial clefting, meaning the spinous cells of the epithelium break apart, a phenomenon known as acantholysis. This is because the desmosomes are attacked. In pemphigoid, the epitheium remains intact, but is entirely "unzipped" from the underlying connective tissue bed, or lamina propria, because the hemidesmosomes are attacked. Also apparent in pemphigus is a "tombstone appearance" of the basal cell layer and Tzanck cells.
Direct immunoflourescence on the biopsy skin sample can be used to detect desmoglein antibodies in the skin. The presence of these antibodies indicates pemphigus. Indirect immunofluorescence and ELISA can measure desmoglein antibodies in blood serum.
# Treatment
If not treated, pemphigus is fatal, due to overwhelming systemic infection. The most common treatment is the administration of oral steroids, especially prednisone. Recently, there has been great promise of surviving some forms of pemphigus (especially PNP) by using a pooled blood product known as gamma globulin or IVIG. Mild cases sometimes respond to the application of topical steroids. In 2007, a clinical trial including a one-week treatment with Rituximab, a monoclonal chimaeric Anti-CD20-Antibody, approved by the FDA for the treatment of B-Cell-Non-Hodgkin-Lymphoma and severe cases of rheumatoid arthritis, showed a remission in 18 of 21 otherwise untreatable, severe cases of Pemphigus vulgaris.
All of these drugs may cause severe side effects, so the patient should be closely monitored by doctors. Once the outbreaks are under control, dosage is often reduced, to lessen side effects.
If paraneoplastic pemphigus is diagnosed with pulmonary disease, a powerful cocktail of immune suppressant drugs is sometimes used in an attempt to halt the rapid progression of bronchiolitis obliterans. Some drugs used include solumedrol, ciclosporin, azathioprine, and in rare instances, extremely controlled use of thalidomide in eligible patients. Immune phoresis procedures are also a possible treatment.
If skin lesions do become infected, antibiotics may be used for treatment. In addition, talcum powder is helpful to prevent oozing sores from adhering to bedsheets and clothes.
# Pemphigus in domestic animals
Pemphigus foliaceus has been recognized in pet dogs, cats and horses and is the most common autoimmune skin disease diagnosed in veterinary medicine. Pemphigus foliaceus in animals produces clusters of small vesicles that quickly evolve into pustules. Pustules may rupture, forming erosions or become crusted. Left untreated, pemphigus foliaceus in animals is life-threatening leading to loss of condition and secondary infection.
Pemphigus vulgaris is a very rare disorder described in pet dogs and cats. Paraneoplastic pemphigus has been identified in pet dogs. | Pemphigus
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pemphigus is an autoimmune disorder that causes blistering and raw sores on skin and mucous membranes. As with other autoimmune disorders, it is caused when the body's defenses mistake its own tissues as foreign, and attack the cells. This particular autoimmune reaction is sometimes associated with the use of Penicillamine. Pemphigus is derived from the Greek pemphix, meaning bubble or blister.
# Types
There are three types of pemphigus which vary in severity: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus.
- The most common form of the disorder is pemphigus vulgaris (ICD-10 L10.0). It occurs when antibodies attack Desmoglein 3, a protein that keeps cells bound together. Thus, cells simply fall apart, causing skin to slough off. Although pemphigus vulgaris may occur at any age, it is quite rare in children, and most common in the middle aged and elderly. Sores often originate in the mouth, making eating difficult and uncomfortable. Pemphigus vulgaris often affects people between the ages of 40-60, and mainly of Jewish, Middle Eastern, or Mediterranean descent. Some patients are associated with myasthenia gravis, but it's unusual.
- Foliaceus is the least severe of the three varieties. Desmoglein 1, the protein that is destroyed by the body's immune system is only found in the top dry layer of the skin, so mouth sores do not occur. Pemphigus foliaceus is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. It is not as painful as pemphigus vulgaris, and is often mis-diagnosed as dermatitis or eczema.
- The least common and most severe type of pemphigus is the neoplastic variety, also known as paraneoplastic pemphigus. This disorder is usually found in conjunction with an already-existing malignancy. Very painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves Bronchiolitis obliterans, a fatal destruction of alveoli in lung tissue. A diagnosis of neoplastic pemphigus may prompt a search for an existing tumor. Sometimes, the tumor is not malignant. In these cases, tumor removal may lead to a remission of the pemphigus. However, any decline in pulmonary function is generally irreversible. With Intravenous Immunoglobulin (IVIG) treatment and aggressive chemotherapy for the underlying lympoma, there are few known survivors of Paraneoplastic Pemphigus with pulmonary involvement (contact information in External Links below).
# Diagnosis
Diagnosis relies on microscopic examination of skin lesion samples. A biopsy of a suspected lesion is taken: a sample of the blistered skin is removed and examined under the microscope to determine if the cells are separated in the manner characteristic of pemphigus. Unlike in the related pemphigoid, pemphigus manifests as intra-epithelial clefting, meaning the spinous cells of the epithelium break apart, a phenomenon known as acantholysis. This is because the desmosomes are attacked. In pemphigoid, the epitheium remains intact, but is entirely "unzipped" from the underlying connective tissue bed, or lamina propria, because the hemidesmosomes are attacked. Also apparent in pemphigus is a "tombstone appearance" of the basal cell layer and Tzanck cells.
Direct immunoflourescence on the biopsy skin sample can be used to detect desmoglein antibodies in the skin. The presence of these antibodies indicates pemphigus. Indirect immunofluorescence and ELISA can measure desmoglein antibodies in blood serum.
# Treatment
If not treated, pemphigus is fatal, due to overwhelming systemic infection. The most common treatment is the administration of oral steroids, especially prednisone. Recently, there has been great promise of surviving some forms of pemphigus (especially PNP) by using a pooled blood product known as gamma globulin or IVIG. Mild cases sometimes respond to the application of topical steroids. In 2007, a clinical trial including a one-week treatment with Rituximab, a monoclonal chimaeric Anti-CD20-Antibody, approved by the FDA for the treatment of B-Cell-Non-Hodgkin-Lymphoma and severe cases of rheumatoid arthritis, showed a remission in 18 of 21 otherwise untreatable, severe cases of Pemphigus vulgaris.[1]
All of these drugs may cause severe side effects, so the patient should be closely monitored by doctors. Once the outbreaks are under control, dosage is often reduced, to lessen side effects.
If paraneoplastic pemphigus is diagnosed with pulmonary disease, a powerful cocktail of immune suppressant drugs is sometimes used in an attempt to halt the rapid progression of bronchiolitis obliterans. Some drugs used include solumedrol, ciclosporin, azathioprine, and in rare instances, extremely controlled use of thalidomide in eligible patients. Immune phoresis procedures are also a possible treatment.
If skin lesions do become infected, antibiotics may be used for treatment. In addition, talcum powder is helpful to prevent oozing sores from adhering to bedsheets and clothes.
# Pemphigus in domestic animals
Pemphigus foliaceus has been recognized in pet dogs, cats and horses and is the most common autoimmune skin disease diagnosed in veterinary medicine. Pemphigus foliaceus in animals produces clusters of small vesicles that quickly evolve into pustules. Pustules may rupture, forming erosions or become crusted. Left untreated, pemphigus foliaceus in animals is life-threatening leading to loss of condition and secondary infection.
Pemphigus vulgaris is a very rare disorder described in pet dogs and cats. Paraneoplastic pemphigus has been identified in pet dogs. | https://www.wikidoc.org/index.php/Pemphigus | |
a2f0a7cf81e2eeedd8e83fb8509c6a6c6f4be173 | wikidoc | Pentacene | Pentacene
Pentacene is an polycyclic aromatic hydrocarbon molecule consisting of 5 linearly-fused benzene rings. It has the appearance of a dark-blue powder. It is an organic semiconductor. It is sensitive to light and oxygen. It is a purple powder, but its oxidation product is greenish. Most commercial samples of pentacene are greenish due to oxidized outer layer. Vacuum sublimation or adsorption chromatography are used to purify pentacene.
Pentacene is a promising candidate for the use in organic thin film transistors and OFETs. It is one of the
most thoroughly investigated conjugated organic molecules with a high application potential due to a hole mobility in OFETs of up to 5.5 cm2V-1s-1 (almost comparable to amorphous silicon).
Combined with buckminsterfullerene Pentacene is used in the development of organic photovoltaic devices.
Pentacene is one of a series of linear acenes, the previous one being tetracene ( four fused benzene rings) and the next one being hexacene (six fused benzene rings).
# Synthesis
Pentacenes can be prepared in the laboratory by extrusion of a small volatile component. In one such experimental procedure carbon monoxide is liberated from a precursor at 150°C. The precursor is reported to have some solubility in chloroform and is therefore amiable to spin coating. Pentacene is reported to be soluble in hot chlorinated benzenes, such as 1,2,4-trichlorobenzene, from which it can be recrystallized to form platelets
# Pentacene derivatives
Although Pentacene looks just like any aromatic compound such as anthracene its aromatic properties are ill defined and for this reason the compound and its derivatives are topic of research.
A tautomeric chemical equilibrium exists between 6-methylene-6,13-dihydropentacene and 6-methylpentacene.
This equilibrium is entirely in favor of the methylene compound. Only by heating to a solution of the compound to 200°C does a small amount of the pentacane develop as evidenced by the emergence of a red-violet color. According to one study the reaction mechanism for this equilibrium is not based on an intramolecular 1,5-hydride shift but on a bimolecular free radical hydrogen migration. In contrast, isotoluenes with the same central chemical motif easily aromatize.
Pentacene reacts with elemental sulfur in 1,2,4-trichlorobenzene to the compound hexathiapentacene. X-ray crystallography shows that all the carbon-to-sulfur bond lengths are roughly equal (170 picometer) and from there it follows that resonance structures B and C with complete charge separation are more significant than structure A.
In the crystal phase the molecules display aromatic stacking interactions whereby the distance between some sulfur atoms on neighboring molecules can become less (337 pm) than the sum of two Van der Waals radii (180 pm)
Like the related tetrathiafulvalene, this compound is studied in the field of organic semiconductors.
The acenes may appear as planar and rigid molecules, but in fact they can be very distorted. The pentacene depicted below:
has an end-to end twist of 144° and is sterically stabilized by the six phenyl groups. The compound can be resolved into its two enantiomers with an unusually high reported optical rotation of 7400° although racemization takes place with a chemical half-life of 9 hours.
# Other uses
Pentacenes are examined as potential dichroic dyes. The pentacenoquinone displayed below is fluorescent and when mixed with liquid crystal E7 mixture a dichroic ratio of 8 is reached. The longer the acene the better it is able to align itself in a nematic liquid crystal phase. | Pentacene
Template:Chembox new
Pentacene is an polycyclic aromatic hydrocarbon molecule consisting of 5 linearly-fused benzene rings. It has the appearance of a dark-blue powder. It is an organic semiconductor. It is sensitive to light and oxygen. It is a purple powder, but its oxidation product is greenish. Most commercial samples of pentacene are greenish due to oxidized outer layer. Vacuum sublimation or adsorption chromatography are used to purify pentacene.
Pentacene is a promising candidate for the use in organic thin film transistors and OFETs. It is one of the
most thoroughly investigated conjugated organic molecules with a high application potential due to a hole mobility in OFETs of up to 5.5 cm2V-1s-1 (almost comparable to amorphous silicon).[1]
Combined with buckminsterfullerene Pentacene is used in the development of organic photovoltaic devices.[2] [3]
Pentacene is one of a series of linear acenes, the previous one being tetracene ( four fused benzene rings) and the next one being hexacene (six fused benzene rings).
# Synthesis
Pentacenes can be prepared in the laboratory by extrusion of a small volatile component. In one such experimental procedure carbon monoxide is liberated from a precursor at 150°C.[4] The precursor is reported to have some solubility in chloroform and is therefore amiable to spin coating. Pentacene is reported to be soluble in hot chlorinated benzenes, such as 1,2,4-trichlorobenzene, from which it can be recrystallized to form platelets
# Pentacene derivatives
Although Pentacene looks just like any aromatic compound such as anthracene its aromatic properties are ill defined and for this reason the compound and its derivatives are topic of research.
A tautomeric chemical equilibrium exists between 6-methylene-6,13-dihydropentacene and 6-methylpentacene.
This equilibrium is entirely in favor of the methylene compound. Only by heating to a solution of the compound to 200°C does a small amount of the pentacane develop as evidenced by the emergence of a red-violet color. According to one study[5] the reaction mechanism for this equilibrium is not based on an intramolecular 1,5-hydride shift but on a bimolecular free radical hydrogen migration. In contrast, isotoluenes with the same central chemical motif easily aromatize.
Pentacene reacts with elemental sulfur in 1,2,4-trichlorobenzene to the compound hexathiapentacene.[6] X-ray crystallography shows that all the carbon-to-sulfur bond lengths are roughly equal (170 picometer) and from there it follows that resonance structures B and C with complete charge separation are more significant than structure A.
In the crystal phase the molecules display aromatic stacking interactions whereby the distance between some sulfur atoms on neighboring molecules can become less (337 pm) than the sum of two Van der Waals radii (180 pm)
Like the related tetrathiafulvalene, this compound is studied in the field of organic semiconductors.
The acenes may appear as planar and rigid molecules, but in fact they can be very distorted. The pentacene depicted below:[7]
has an end-to end twist of 144° and is sterically stabilized by the six phenyl groups. The compound can be resolved into its two enantiomers with an unusually high reported optical rotation of 7400° although racemization takes place with a chemical half-life of 9 hours.
# Other uses
Pentacenes are examined as potential dichroic dyes. The pentacenoquinone displayed below is fluorescent and when mixed with liquid crystal E7 mixture a dichroic ratio of 8 is reached.[8][9] The longer the acene the better it is able to align itself in a nematic liquid crystal phase.
# External links
- facts about pentacene, retrieved Apr. 17, 2006
- [2], retrieved May 2, 2007 | https://www.wikidoc.org/index.php/Pentacene | |
0f3bbce69d44e3d06b2397e09200dad55a7544da | wikidoc | Peramivir | Peramivir
Peramivir is an experimental antiviral drug being developed by Biocryst Pharmaceuticals to treat influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. The development of peramivir is supported by the US Department of Health and Human Services as part of the government's effort to prepare for a flu pandemic.
The drug has had a long history. An oral formulation was abandoned by Johnson and Johnson due to poor bioavailability.
BioCryst is now developing a injectable version, in partnership with Green Cross Pharmaceuticals in South Korea and with Shionogi Pharmaceuticals in Japan. The drug is in Phase II studies.
Experimental data indicate that peramivir may have useful activity against many viruses of interest, including H5N1 (avian bird flu) , hepatitis B, polio, measles and smallpox. Peramivir is active in a hamster model of yellow fever, a finding which is not surprising, given the familial relationship of yellow fever and hepatitis C viruses as flaviviridae. Peramivir is active against other important flaviviridae such as West Nile virus and dengue fever.Template:Facts
# Sources
"HHS Pursues Advance Development of New Influenza Antiviral Drug" (Press release). US Department of Health and Human Services. 2007-01-04. Retrieved 2007-05-25. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
Pollack, Andrew (2005-10-07). "Talk of Bird Flu Pandemic Revives Interest in Passed-Over Drugs". New York Times. Retrieved 2007-05-25. Check date values in: |date= (help)
"Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza". National Institutes of Health. 2007-03-16. Retrieved 2007-05-25. Check date values in: |date= (help)
"Evaluation of the Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-Threatening Influenza". National Institutes of Health. 2007-03-28. Retrieved 2007-05-25. Check date values in: |date= (help) | Peramivir
Peramivir is an experimental antiviral drug being developed by Biocryst Pharmaceuticals to treat influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. The development of peramivir is supported by the US Department of Health and Human Services as part of the government's effort to prepare for a flu pandemic.[1]
The drug has had a long history. An oral formulation was abandoned by Johnson and Johnson due to poor bioavailability.[2]
BioCryst is now developing a injectable version, in partnership with Green Cross Pharmaceuticals in South Korea and with Shionogi Pharmaceuticals in Japan. The drug is in Phase II studies.[3]
[4]
Experimental data indicate that peramivir may have useful activity against many viruses of interest, including H5N1 (avian bird flu) , hepatitis B, polio, measles and smallpox. Peramivir is active in a hamster model of yellow fever, a finding which is not surprising, given the familial relationship of yellow fever and hepatitis C viruses as flaviviridae. Peramivir is active against other important flaviviridae such as West Nile virus and dengue fever.Template:Facts
# Sources
- ↑
"HHS Pursues Advance Development of New Influenza Antiviral Drug" (Press release). US Department of Health and Human Services. 2007-01-04. Retrieved 2007-05-25. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑
Pollack, Andrew (2005-10-07). "Talk of Bird Flu Pandemic Revives Interest in Passed-Over Drugs". New York Times. Retrieved 2007-05-25. Check date values in: |date= (help)
- ↑
"Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza". National Institutes of Health. 2007-03-16. Retrieved 2007-05-25. Check date values in: |date= (help)
- ↑
"Evaluation of the Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-Threatening Influenza". National Institutes of Health. 2007-03-28. Retrieved 2007-05-25. Check date values in: |date= (help)
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Peramivir | |
352312af8538a619459ce964794f616f43cc001a | wikidoc | Perfusion | Perfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuse" meaning to "pour over or through."
Tests of adequate perfusion are a part of patient triage performed by medical or emergency personnel in a mass casualty incident.
# Calculation
Perfusion ("F") can be measured with the following formula, where Pa is mean arterial pressure, Pv is mean venous pressure, and R is vascular resistance:
F = \frac{ P_A - P_V }{ R}
The term "Pa - Pv" is sometimes presented as "ΔP", for the change in pressure.
The terms "perfusion" and "perfusion pressure" are sometimes used interchangeably, but the equation should make clear that resistance can have an effect on the perfusion, but not on the perfusion pressure.
# Overperfusion and underperfusion
The terms "overperfusion" and "underperfusion" are measured relative to the average level of perfusion across all tissues in an individual body, and the terms should not be confused with hypoperfusion and "hyperperfusion", which measure the perfusion level to the tissue's current need.
Tissues like the skin are considered overperfused and receive more blood than would be expected to meet the metabolic needs of the tissue. In the case of the skin, extra blood flow is used for thermoregulation. In addition to delivering oxygen, the blood helps dissipate heat by redirecting warm blood close to the surface where it can cool the body through the sweating and thermal radiation.
# Measurement using fMRI
Two main categories of functional magnetic resonance imaging (fMRI) techniques can be used to measure tissue perfusion in vivo.
- The first is based on the use of injected contrast agent that changes the magnetic susceptibility of blood and thereby the MR signal which is repeatedly measured during bolus passage.
- The other category is based on Arterial spin labeling (ASL), where arterial blood is magnetically tagged before it enters into the tissue of interest and the amount of labeling is measured and compared to a control recording obtained without spin labeling. | Perfusion
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuse" meaning to "pour over or through."
Tests of adequate perfusion are a part of patient triage performed by medical or emergency personnel in a mass casualty incident.
# Calculation
Perfusion ("F") can be measured with the following formula, where Pa is mean arterial pressure, Pv is mean venous pressure, and R is vascular resistance: [1]
<math>F = \frac{ P_A - P_V }{ R} </math>
The term "Pa - Pv" is sometimes presented as "ΔP", for the change in pressure.[2]
The terms "perfusion" and "perfusion pressure" are sometimes used interchangeably, but the equation should make clear that resistance can have an effect on the perfusion, but not on the perfusion pressure.
# Overperfusion and underperfusion
The terms "overperfusion" and "underperfusion" are measured relative to the average level of perfusion across all tissues in an individual body, and the terms should not be confused with hypoperfusion and "hyperperfusion", which measure the perfusion level to the tissue's current need.
Tissues like the skin are considered overperfused and receive more blood than would be expected to meet the metabolic needs of the tissue. In the case of the skin, extra blood flow is used for thermoregulation. In addition to delivering oxygen, the blood helps dissipate heat by redirecting warm blood close to the surface where it can cool the body through the sweating and thermal radiation.
# Measurement using fMRI
Two main categories of functional magnetic resonance imaging (fMRI) techniques can be used to measure tissue perfusion in vivo.
- The first is based on the use of injected contrast agent that changes the magnetic susceptibility of blood and thereby the MR signal which is repeatedly measured during bolus passage.
- The other category is based on Arterial spin labeling (ASL), where arterial blood is magnetically tagged before it enters into the tissue of interest and the amount of labeling is measured and compared to a control recording obtained without spin labeling. | https://www.wikidoc.org/index.php/Perfusion | |
033cb1fdd2f4865dfe5ce52882789c8e4a83aeb1 | wikidoc | Pergolide | Pergolide
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Pergolide is an antiparkinsonian, autonomic, central nervous system agent, dopamine agonist that is FDA approved for the treatment of Parkinson's disease as an adjunctive treatment with carbidopa/levodopa. There is a Black Box Warning for this drug as shown here. Common adverse reactions include dyskinesia, hallucinations, somnolence, insomnia, nausea, constipation, diarrhea, dyspepsia and rhinitis.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Administration of Pergolide should be initiated with a daily dosage of 0.05 mg for the first 2 days. The dosage should then be gradually increased by 0.1 or 0.15 mg/day every third day over the next 12 days of therapy. The dosage may then be increased by 0.25 mg/day every third day until an optimal therapeutic dosage is achieved.
- Pergolide is usually administered in divided doses 3 times per day. During dosage titration, the dosage of concurrent l-dopa/carbidopa may be cautiously decreased.
- In clinical studies, the mean therapeutic daily dosage of Pergolide was 3 mg/day. The average concurrent daily dosage of l-dopa/carbidopa (expressed as l-dopa) was approximately 650 mg/day. The efficacy of Pergolide at doses above 5 mg/day has not been systematically evaluated. Doses of pergolide above 5 mg/day are not recommended.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pergolide in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pergolide in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Pergolide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pergolide in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pergolide in pediatric patients.
# Contraindications
- Pergolide is contraindicated in patients who are hypersensitive to this drug or other ergot derivatives.
# Warnings
### Cardiac Valvulopathy and Fibrotic Complications
- Falling Asleep During Activities of Daily Living—Patients treated with Pergolide have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on Pergolide some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events had been reported as late as 1 year after the initiation of treatment.
- Somnolence is a common occurrence in patients receiving Pergolide — Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
- Before initiating treatment with Pergolide, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with Pergolide such as concomitant sedating medications or the presence of sleep disorders. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require participation (e.g., conversations, eating, etc.), Pergolide should ordinarily be discontinued. *If a decision is made to continue Pergolide, patients should be advised to not drive and to avoid other potentially dangerous activities.
While dose reduction may reduce the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
- While dose reduction may reduce the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
- Symptomatic Hypotension — In clinical trials, approximately 10% of patients taking pergolide with l-dopa versus 7% taking placebo with l-dopa experienced symptomatic orthostatic hypotension and/or sustained hypotension, especially during initial treatment. With gradual dosage titration, tolerance to the hypotension usually develops. It is therefore important to warn patients of the risk, to begin therapy with low doses, and to increase the dosage in carefully adjusted increments over a period of 3 to 4 weeks.
- Hallucinosis— In controlled trials, pergolide with l-dopa caused hallucinosis in about 14% of patients as opposed to 3% taking placebo with l-dopa. This was of sufficient severity to cause discontinuation of treatment in about 3% of those enrolled; tolerance to this untoward effect was not observed.
- Fatalities— In the placebo-controlled trial, 2 of 187 patients treated with placebo died as compared with 1 of 189 patients treated with pergolide. Of the 2299 patients treated with pergolide in premarketing studies evaluated as of October 1988, 143 died while on the drug or shortly after discontinuing it. Because the patient population under evaluation was elderly, ill, and at high risk for death, it seems unlikely that pergolide played any role in these deaths, but the possibility that pergolide shortens survival of patients cannot be excluded with absolute certainty.
- In particular, a case-by-case review of the clinical course of the patients who died failed to disclose any unique set of signs, symptoms, or laboratory results that would suggest that treatment with pergolide caused their deaths. Sixty-eight percent (68%) of the patients who died were 65 years of age or older. No death (other than a suicide) occurred within the first month of treatment; most of the patients who died had been on pergolide for years. A relative frequency of the causes of death by organ system are: Pulmonary failure/Pneumonia, 35%; Cardiovascular, 30%; Cancer, 11%; Unknown, 8.4%; Infection, 3.5%; Extrapyramidal syndrome, 3.5%; Stroke, 2.1%; Dysphagia, 2.1%; Injury, 1.4%; Suicide, 1.4%; Dehydration, 0.7%; Glomerulonephritis, 0.7%.
# Adverse Reactions
## Clinical Trials Experience
### Commonly Observed
- In premarketing clinical trials, the most commonly observed adverse events associated with use of pergolide which were not seen at an equivalent incidence among placebo-treated patients were: nervous system complaints, including dyskinesia, hallucinations, somnolence, insomnia; digestive complaints, including nausea, constipation, diarrhea, dyspepsia; and respiratory system complaints, including rhinitis.
- Associated With Discontinuation of Treatment: Twenty-seven percent (27%) of approximately 1200 patients receiving pergolide for treatment of Parkinson's disease in premarketing clinical trials in the US and Canada discontinued treatment due to adverse events. The events most commonly causing discontinuation were related to the nervous system (15.5%), primarily hallucinations (7.8%) and confusion (1.8%).
### Fatalities
- Incidence in Controlled Clinical Trials: The table that follows enumerates adverse events that occurred at a frequency of 1% or more among patients taking pergolide who participated in the premarketing controlled clinical trials comparing pergolide with placebo. In a double-blind, controlled study of 6 months’ duration, patients with Parkinson’s disease were continued on l-dopa/carbidopa and were randomly assigned to receive either pergolide or placebo as additional therapy. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.
- Events Observed During the Premarketing Evaluation of Pergolide— This section reports event frequencies evaluated as of October 1988 for adverse events occurring in a group of approximately 1800 patients who took multiple doses of pergolide. The conditions and duration of exposure to pergolide varied greatly, involving well-controlled studies as well as experience in open and uncontrolled clinical settings. In the absence of appropriate controls in some of the studies, a causal relationship between these events and treatment with pergolide cannot be determined.
- The following enumeration by organ system describes events in terms of their relative frequency of reporting in the data base. Events of major clinical importance are also described in the Warnings and Precautions sections.
- The following definitions of frequency are used: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
### Body as a Whole
- Frequent: headache, asthenia, accidental injury, pain, abdominal pain, chest pain, back pain, flu syndrome, neck pain, fever
- Infrequent: facial edema, chills, enlarged abdomen, malaise, neoplasm, hernia, pelvic pain, sepsis, cellulitis, moniliasis, abscess, jaw pain, hypothermia
- Rare: acute abdominal syndrome, LE syndrome
### Cardiovascular System
- Frequent: postural hypotension, syncope, hypertension, palpitations, vasodilatations, congestive heart failure
- Infrequent: myocardial infarction, tachycardia, heart arrest, abnormal electrocardiogram, angina pectoris, thrombophlebitis, bradycardia, ventricular extrasystoles, cerebrovascular accident, ventricular tachycardia, cerebral ischemia, atrial fibrillation, varicose vein, pulmonary embolus, AV block, shock
- Rare: vasculitis, pulmonary hypertension, pericarditis, migraine, heart block, cerebral hemorrhage.
### Digestive System
- Frequent: nausea, vomiting, dyspepsia, diarrhea, constipation, dry mouth, dysphagia
- Infrequent: flatulence, abnormal liver function tests, increased appetite, salivary gland enlargement, thirst, gastroenteritis, gastritis, periodontal abscess, intestinal obstruction, nausea and vomiting, gingivitis, esophagitis, cholelithiasis, tooth caries, hepatitis, stomach ulcer, melena, hepatomegaly, hematemesis, eructation
- Rare: sialadenitis, peptic ulcer, pancreatitis, jaundice, glossitis, fecal incontinence, duodenitis, colitis, cholecystitis, aphthous stomatitis, esophageal ulcer.
### Endocrine System
- Infrequent: hypothyroidism, adenoma, diabetes mellitus, ADH inappropriate
- Rare: endocrine disorder, thyroid adenoma.
### Hemic and Lymphatic System
- Frequent: anemia
- Infrequent: leukopenia, lymphadenopathy, leukocytosis, thrombocytopenia, petechia, megaloblastic anemia, cyanosis
- Rare: purpura, lymphocytosis, eosinophilia, thrombocythemia, acute lymphoblastic leukemia, polycythemia, splenomegaly.
### Metabolic and Nutritional System
- Frequent: peripheral edema, weight loss, weight gain
- Infrequent: dehydration, hypokalemia, hypoglycemia, iron deficiency anemia, hyperglycemia, gout, hypercholesterolemia
- Rare: electrolyte imbalance, cachexia, acidosis, hyperuricemia.
### Musculoskeletal System
- Frequent: twitching, myalgia, arthralgia
- Infrequent: bone pain, tenosynovitis, myositis, bone sarcoma, arthritis
- Rare: osteoporosis, muscle atrophy, osteomyelitis.
### Nervous System
- Frequent: dyskinesia, dizziness, hallucinations, confusion, somnolence, insomnia, dystonia, paresthesia, depression, anxiety, tremor, akinesia, extrapyramidal syndrome, abnormal gait, abnormal dreams, incoordination, psychosis, personality disorder, nervousness, choreoathetosis, amnesia, paranoid reaction, abnormal thinking
- Infrequent: akathisia, neuropathy, neuralgia, hypertonia, delusions, convulsion, libido increased, euphoria, emotional lability, libido decreased, vertigo, myoclonus, coma, apathy, paralysis, neurosis, hyperkinesia, ataxia, acute brain syndrome, torticollis, meningitis, manic reaction, hypokinesia, hostility, agitation, hypotonia
- Rare: stupor, neuritis, intracranial hypertension, hemiplegia, facial paralysis, brain edema, myelitis, hallucinations and confusion after abrupt discontinuation.
### Respiratory System
- Frequent: rhinitis, dyspnea, pneumonia, pharyngitis, cough increased
- Infrequent: epistaxis, hiccup, sinusitis, bronchitis, voice alteration, hemoptysis, asthma, lung edema, pleural effusion, laryngitis, emphysema, apnea, hyperventilation
- Rare: pneumothorax, lung fibrosis, larynx edema, hypoxia, hypoventilation, hemothorax, carcinoma of lung.
### Skin and Appendages System
- Frequent: sweating, rash
- Infrequent: skin discoloration, pruritus, acne, skin ulcer, alopecia, dry skin, skin carcinoma, seborrhea, hirsutism, herpes simplex, eczema, fungal dermatitis, herpes zoster
- Rare: vesiculobullous rash, subcutaneous nodule, skin nodule, skin benign neoplasm, lichenoid dermatitis.
### Special Senses System
- Frequent: abnormal vision, diplopia
- Infrequent: otitis media, conjunctivitis, tinnitus, deafness, taste perversion, ear pain, eye pain, glaucoma, eye hemorrhage, photophobia, visual field defect
- Rare: blindness, cataract, retinal detachment, retinal vascular disorder.
### Urogenital System
- Frequent: urinary tract infection, urinary frequency, urinary incontinence, hematuria, dysmenorrhea
- Infrequent: dysuria, breast pain, menorrhagia, impotence, cystitis, urinary retention, abortion, vaginal hemorrhage, vaginitis, priapism, kidney calculus, fibrocystic breast, lactation, uterine hemorrhage, urolithiasis, salpingitis, pyuria, metrorrhagia, menopause, kidney failure, breast carcinoma, cervical carcinoma
- Rare: amenorrhea, bladder carcinoma, breast engorgement, epididymitis, hypogonadism, leukorrhea, nephrosis, pyelonephritis, urethral pain, uricaciduria, withdrawal bleeding.
## Postmarketing Experience
### Postintroduction Reports
- Voluntary reports of adverse events temporally associated with pergolide that have been received since market introduction and which may have no causal relationship with the drug, include the following: neuroleptic malignant syndrome and Raynaud’s phenomenon.
# Drug Interactions
- Dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthines) or metoclopramide, ordinarily should not be administered concurrently with Pergolide (a dopamine agonist); these agents may diminish the effectiveness of Pergolide.
- Because pergolide is approximately 90% bound to plasma proteins, caution should be exercised if pergolide is coadministered with other drugs known to affect protein binding.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies were conducted in mice at doses of 5, 16, and 45 mg/kg/day and in rabbits at doses of 2, 6, and 16 mg/kg/day. The highest doses tested in mice and rabbits were 375 and 133 times the 6 mg/day maximum human dose administered in controlled clinical trials. In these studies, there was no evidence of harm to the fetus due to pergolide.
- There are, however, no adequate and well-controlled studies in pregnant women. Among women who received pergolide for endocrine disorders in premarketing studies, there were 33 pregnancies that resulted in healthy babies and 6 pregnancies that resulted in congenital abnormalities (3 major, 3 minor); a causal relationship has not been established. Because human data are limited and because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pergolide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Pergolide during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. The pharmacologic action of pergolide suggests that it may interfere with lactation. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions to pergolide in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- Of the total number of subjects in clinical studies of pergolide, 78 were 65 and over. There were no apparent differences in efficacy between these subjects and younger subjects. There was an increased incidence of confusion, somnolence, and peripheral edema in patients 65 and over. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
### Gender
There is no FDA guidance on the use of Pergolide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Pergolide with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Pergolide in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Pergolide in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pergolide in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Pergolide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Pergolide Administration in the drug label.
### Monitoring
There is limited information regarding Pergolide Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Pergolide and IV administrations.
# Overdosage
- There is no clinical experience with massive overdosage. The largest overdose involved a young hospitalized adult patient who was not being treated with pergolide but who intentionally took 60 mg of the drug. He experienced vomiting, hypotension, and agitation. Another patient receiving a daily dosage of 7 mg of pergolide unintentionally took 19 mg/day for 3 days, after which his vital signs were normal but he experienced severe hallucinations. Within 36 hours of resumption of the prescribed dosage level, the hallucinations stopped. One patient unintentionally took 14 mg/day for 23 days instead of her prescribed 1.4 mg/day dosage. She experienced severe involuntary movements and tingling in her arms and legs. Another patient who inadvertently received 7 mg instead of the prescribed 0.7 mg experienced palpitations, hypotension, and ventricular extrasystoles. The highest total daily dose (prescribed for several patients with refractory Parkinson's disease) has exceeded 30 mg.
- Symptoms— Animal studies indicate that the manifestations of overdosage in man might include nausea, vomiting, convulsions, hypotension, and CNS stimulation. The oral median lethal doses in mice and rats were 54 and 15 mg/kg respectively.
- Treatment— To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
- Management of overdosage may require supportive measures to maintain arterial blood pressure. Cardiac function should be monitored; an antiarrhythmic agent may be necessary. If signs of CNS stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdose has not been assessed.
- Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.
- There is no experience with dialysis or hemoperfusion, and these procedures are unlikely to be of benefit.
# Pharmacology
## Mechanism of Action
There is limited information regarding Pergolide Mechanism of Action in the drug label.
## Structure
- Pergolide mesylate is chemically designated as 8β-(Methylthio)methyl-6-propylergoline monomethanesulfonate; the structural formula is as follows:
The empirical formula is C19H26N2S∙CH4O3S, representing a molecular weight of 410.60.
## Pharmacodynamics
- Pergolide is a potent dopamine agonist. Pergolide is 10 to 1000 times more potent than bromocriptine on a milligram per milligram basis in various in vitro and in vivo test systems. Pergolide inhibits the secretion of prolactin in humans; it causes a transient rise in serum concentrations of growth hormone and a decrease in serum concentrations of luteinizing hormone. In Parkinson's disease, pergolide is believed to exert its therapeutic effect by directly stimulating postsynaptic dopamine receptors in the nigrostriatal system.
## Pharmacokinetics
- Information on oral systemic bioavailability of pergolide is unavailable because of the lack of a sufficiently sensitive assay to detect the drug after the administration of a single dose. However, following oral administration of 14C radiolabeled pergolide, approximately 55% of the administered radioactivity can be recovered from the urine and 5% from expired CO2, suggesting that a significant fraction is absorbed. Nothing can be concluded about the extent of presystemic clearance, if any.
- Pergolide is approximately 90% bound to plasma proteins. This extent of protein binding may be important to consider when pergolide is coadministered with other drugs known to affect protein binding.
- Data on postabsorption distribution of pergolide are unavailable.
- At least 10 metabolites have been detected, including N-despropylpergolide, pergolide sulfoxide, and pergolide sulfone.
- Pergolide sulfoxide and pergolide sulfone are dopamine agonists in animals. The other detected metabolites have not been identified and it is not known whether any other metabolites are active pharmacologically.
- The major route of excretion is the kidney.
## Nonclinical Toxicology
- A 2-year carcinogenicity study was conducted in mice using dietary levels of pergolide equivalent to oral doses of 0.6, 3.7, and 36.4 mg/kg/day in males and 0.6, 4.4, and 40.8 mg/kg/day in females. A 2-year study in rats was conducted using dietary levels equivalent to oral doses of 0.04, 0.18, and 0.88 mg/kg/day in males and 0.05, 0.28, and 1.42 mg/kg/day in females. The highest doses tested in the mice and rats were approximately 340 and 12 times the maximum human oral dose administered in controlled clinical trials (6 mg/day equivalent to 0.12 mg/kg/day).
- A low incidence of uterine neoplasms occurred in both rats and mice. Endometrial adenomas and carcinomas were observed in rats. Endometrial sarcomas were observed in mice. The occurrence of these neoplasms is probably attributable to the high estrogen/progesterone ratio that would occur in rodents as a result of the prolactin-inhibiting action of pergolide. The endocrine mechanisms believed to be involved in the rodents are not present in humans. However, even though there is no known correlation between uterine malignancies occurring in pergolide-treated rodents and human risk, there are no human data to substantiate this conclusion.
- Pergolide was evaluated for mutagenic potential in a battery of tests that included an Ames bacterial mutation assay, a DNA repair assay in cultured rat hepatocytes, an in vitro mammalian cell gene mutation assay in cultured L5178Y cells, and a determination of chromosome alteration in bone marrow cells of Chinese hamsters. A weak mutagenic response was noted in the mammalian cell gene mutation assay only after metabolic activation with rat liver microsomes. No mutagenic effects were obtained in the 2 other in vitro assays and in the in vivo assay. The relevance of these findings in humans is unknown.
- A fertility study in male and female mice showed that fertility was maintained at 0.6 and 1.7 mg/kg/day but decreased at 5.6 mg/kg/day. Prolactin has been reported to be involved in stimulating and maintaining progesterone levels required for implantation in mice and, therefore, the impaired fertility at the high dose may have occurred because of depressed prolactin levels.
# Clinical Studies
There is limited information regarding Pergolide Clinical Studies in the drug label.
# How Supplied
Tablets (modified rectangle shape, scored):
- 0.05 mg, ivory, debossed with A 024, in bottles of 30 (UC5336) — NDC 0187-0839-01
- 0.25 mg, green, debossed with A 025, in bottles of 100 (UC5337) — NDC 0187-0840-02
- 1 mg, pink, debossed with A 026, in bottles of 100 (UC5338) — NDC 0187-0841-02
## Storage
- Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F)
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Pergolide Patient Counseling Information in the drug label.
# Precautions with Alcohol
- Alcohol-Pergolide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Permax
# Look-Alike Drug Names
There is limited information regarding Pergolide Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Pergolide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
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# Black Box Warning
# Overview
Pergolide is an antiparkinsonian, autonomic, central nervous system agent, dopamine agonist that is FDA approved for the treatment of Parkinson's disease as an adjunctive treatment with carbidopa/levodopa. There is a Black Box Warning for this drug as shown here. Common adverse reactions include dyskinesia, hallucinations, somnolence, insomnia, nausea, constipation, diarrhea, dyspepsia and rhinitis.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Administration of Pergolide should be initiated with a daily dosage of 0.05 mg for the first 2 days. The dosage should then be gradually increased by 0.1 or 0.15 mg/day every third day over the next 12 days of therapy. The dosage may then be increased by 0.25 mg/day every third day until an optimal therapeutic dosage is achieved.
- Pergolide is usually administered in divided doses 3 times per day. During dosage titration, the dosage of concurrent l-dopa/carbidopa may be cautiously decreased.
- In clinical studies, the mean therapeutic daily dosage of Pergolide was 3 mg/day. The average concurrent daily dosage of l-dopa/carbidopa (expressed as l-dopa) was approximately 650 mg/day. The efficacy of Pergolide at doses above 5 mg/day has not been systematically evaluated. Doses of pergolide above 5 mg/day are not recommended.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pergolide in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pergolide in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Pergolide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pergolide in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pergolide in pediatric patients.
# Contraindications
- Pergolide is contraindicated in patients who are hypersensitive to this drug or other ergot derivatives.
# Warnings
### Cardiac Valvulopathy and Fibrotic Complications
- Falling Asleep During Activities of Daily Living—Patients treated with Pergolide have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on Pergolide some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events had been reported as late as 1 year after the initiation of treatment.
- Somnolence is a common occurrence in patients receiving Pergolide — Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
- Before initiating treatment with Pergolide, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with Pergolide such as concomitant sedating medications or the presence of sleep disorders. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require participation (e.g., conversations, eating, etc.), Pergolide should ordinarily be discontinued. *If a decision is made to continue Pergolide, patients should be advised to not drive and to avoid other potentially dangerous activities.
While dose reduction may reduce the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
- While dose reduction may reduce the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
- Symptomatic Hypotension — In clinical trials, approximately 10% of patients taking pergolide with l-dopa versus 7% taking placebo with l-dopa experienced symptomatic orthostatic hypotension and/or sustained hypotension, especially during initial treatment. With gradual dosage titration, tolerance to the hypotension usually develops. It is therefore important to warn patients of the risk, to begin therapy with low doses, and to increase the dosage in carefully adjusted increments over a period of 3 to 4 weeks.
- Hallucinosis— In controlled trials, pergolide with l-dopa caused hallucinosis in about 14% of patients as opposed to 3% taking placebo with l-dopa. This was of sufficient severity to cause discontinuation of treatment in about 3% of those enrolled; tolerance to this untoward effect was not observed.
- Fatalities— In the placebo-controlled trial, 2 of 187 patients treated with placebo died as compared with 1 of 189 patients treated with pergolide. Of the 2299 patients treated with pergolide in premarketing studies evaluated as of October 1988, 143 died while on the drug or shortly after discontinuing it. Because the patient population under evaluation was elderly, ill, and at high risk for death, it seems unlikely that pergolide played any role in these deaths, but the possibility that pergolide shortens survival of patients cannot be excluded with absolute certainty.
- In particular, a case-by-case review of the clinical course of the patients who died failed to disclose any unique set of signs, symptoms, or laboratory results that would suggest that treatment with pergolide caused their deaths. Sixty-eight percent (68%) of the patients who died were 65 years of age or older. No death (other than a suicide) occurred within the first month of treatment; most of the patients who died had been on pergolide for years. A relative frequency of the causes of death by organ system are: Pulmonary failure/Pneumonia, 35%; Cardiovascular, 30%; Cancer, 11%; Unknown, 8.4%; Infection, 3.5%; Extrapyramidal syndrome, 3.5%; Stroke, 2.1%; Dysphagia, 2.1%; Injury, 1.4%; Suicide, 1.4%; Dehydration, 0.7%; Glomerulonephritis, 0.7%.
# Adverse Reactions
## Clinical Trials Experience
### Commonly Observed
- In premarketing clinical trials, the most commonly observed adverse events associated with use of pergolide which were not seen at an equivalent incidence among placebo-treated patients were: nervous system complaints, including dyskinesia, hallucinations, somnolence, insomnia; digestive complaints, including nausea, constipation, diarrhea, dyspepsia; and respiratory system complaints, including rhinitis.
- Associated With Discontinuation of Treatment: Twenty-seven percent (27%) of approximately 1200 patients receiving pergolide for treatment of Parkinson's disease in premarketing clinical trials in the US and Canada discontinued treatment due to adverse events. The events most commonly causing discontinuation were related to the nervous system (15.5%), primarily hallucinations (7.8%) and confusion (1.8%).
### Fatalities
- Incidence in Controlled Clinical Trials: The table that follows enumerates adverse events that occurred at a frequency of 1% or more among patients taking pergolide who participated in the premarketing controlled clinical trials comparing pergolide with placebo. In a double-blind, controlled study of 6 months’ duration, patients with Parkinson’s disease were continued on l-dopa/carbidopa and were randomly assigned to receive either pergolide or placebo as additional therapy. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.
- Events Observed During the Premarketing Evaluation of Pergolide— This section reports event frequencies evaluated as of October 1988 for adverse events occurring in a group of approximately 1800 patients who took multiple doses of pergolide. The conditions and duration of exposure to pergolide varied greatly, involving well-controlled studies as well as experience in open and uncontrolled clinical settings. In the absence of appropriate controls in some of the studies, a causal relationship between these events and treatment with pergolide cannot be determined.
- The following enumeration by organ system describes events in terms of their relative frequency of reporting in the data base. Events of major clinical importance are also described in the Warnings and Precautions sections.
- The following definitions of frequency are used: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
### Body as a Whole
- Frequent: headache, asthenia, accidental injury, pain, abdominal pain, chest pain, back pain, flu syndrome, neck pain, fever
- Infrequent: facial edema, chills, enlarged abdomen, malaise, neoplasm, hernia, pelvic pain, sepsis, cellulitis, moniliasis, abscess, jaw pain, hypothermia
- Rare: acute abdominal syndrome, LE syndrome
### Cardiovascular System
- Frequent: postural hypotension, syncope, hypertension, palpitations, vasodilatations, congestive heart failure
- Infrequent: myocardial infarction, tachycardia, heart arrest, abnormal electrocardiogram, angina pectoris, thrombophlebitis, bradycardia, ventricular extrasystoles, cerebrovascular accident, ventricular tachycardia, cerebral ischemia, atrial fibrillation, varicose vein, pulmonary embolus, AV block, shock
- Rare: vasculitis, pulmonary hypertension, pericarditis, migraine, heart block, cerebral hemorrhage.
### Digestive System
- Frequent: nausea, vomiting, dyspepsia, diarrhea, constipation, dry mouth, dysphagia
- Infrequent: flatulence, abnormal liver function tests, increased appetite, salivary gland enlargement, thirst, gastroenteritis, gastritis, periodontal abscess, intestinal obstruction, nausea and vomiting, gingivitis, esophagitis, cholelithiasis, tooth caries, hepatitis, stomach ulcer, melena, hepatomegaly, hematemesis, eructation
- Rare: sialadenitis, peptic ulcer, pancreatitis, jaundice, glossitis, fecal incontinence, duodenitis, colitis, cholecystitis, aphthous stomatitis, esophageal ulcer.
### Endocrine System
- Infrequent: hypothyroidism, adenoma, diabetes mellitus, ADH inappropriate
- Rare: endocrine disorder, thyroid adenoma.
### Hemic and Lymphatic System
- Frequent: anemia
- Infrequent: leukopenia, lymphadenopathy, leukocytosis, thrombocytopenia, petechia, megaloblastic anemia, cyanosis
- Rare: purpura, lymphocytosis, eosinophilia, thrombocythemia, acute lymphoblastic leukemia, polycythemia, splenomegaly.
### Metabolic and Nutritional System
- Frequent: peripheral edema, weight loss, weight gain
- Infrequent: dehydration, hypokalemia, hypoglycemia, iron deficiency anemia, hyperglycemia, gout, hypercholesterolemia
- Rare: electrolyte imbalance, cachexia, acidosis, hyperuricemia.
### Musculoskeletal System
- Frequent: twitching, myalgia, arthralgia
- Infrequent: bone pain, tenosynovitis, myositis, bone sarcoma, arthritis
- Rare: osteoporosis, muscle atrophy, osteomyelitis.
### Nervous System
- Frequent: dyskinesia, dizziness, hallucinations, confusion, somnolence, insomnia, dystonia, paresthesia, depression, anxiety, tremor, akinesia, extrapyramidal syndrome, abnormal gait, abnormal dreams, incoordination, psychosis, personality disorder, nervousness, choreoathetosis, amnesia, paranoid reaction, abnormal thinking
- Infrequent: akathisia, neuropathy, neuralgia, hypertonia, delusions, convulsion, libido increased, euphoria, emotional lability, libido decreased, vertigo, myoclonus, coma, apathy, paralysis, neurosis, hyperkinesia, ataxia, acute brain syndrome, torticollis, meningitis, manic reaction, hypokinesia, hostility, agitation, hypotonia
- Rare: stupor, neuritis, intracranial hypertension, hemiplegia, facial paralysis, brain edema, myelitis, hallucinations and confusion after abrupt discontinuation.
### Respiratory System
- Frequent: rhinitis, dyspnea, pneumonia, pharyngitis, cough increased
- Infrequent: epistaxis, hiccup, sinusitis, bronchitis, voice alteration, hemoptysis, asthma, lung edema, pleural effusion, laryngitis, emphysema, apnea, hyperventilation
- Rare: pneumothorax, lung fibrosis, larynx edema, hypoxia, hypoventilation, hemothorax, carcinoma of lung.
### Skin and Appendages System
- Frequent: sweating, rash
- Infrequent: skin discoloration, pruritus, acne, skin ulcer, alopecia, dry skin, skin carcinoma, seborrhea, hirsutism, herpes simplex, eczema, fungal dermatitis, herpes zoster
- Rare: vesiculobullous rash, subcutaneous nodule, skin nodule, skin benign neoplasm, lichenoid dermatitis.
### Special Senses System
- Frequent: abnormal vision, diplopia
- Infrequent: otitis media, conjunctivitis, tinnitus, deafness, taste perversion, ear pain, eye pain, glaucoma, eye hemorrhage, photophobia, visual field defect
- Rare: blindness, cataract, retinal detachment, retinal vascular disorder.
### Urogenital System
- Frequent: urinary tract infection, urinary frequency, urinary incontinence, hematuria, dysmenorrhea
- Infrequent: dysuria, breast pain, menorrhagia, impotence, cystitis, urinary retention, abortion, vaginal hemorrhage, vaginitis, priapism, kidney calculus, fibrocystic breast, lactation, uterine hemorrhage, urolithiasis, salpingitis, pyuria, metrorrhagia, menopause, kidney failure, breast carcinoma, cervical carcinoma
- Rare: amenorrhea, bladder carcinoma, breast engorgement, epididymitis, hypogonadism, leukorrhea, nephrosis, pyelonephritis, urethral pain, uricaciduria, withdrawal bleeding.
## Postmarketing Experience
### Postintroduction Reports
- Voluntary reports of adverse events temporally associated with pergolide that have been received since market introduction and which may have no causal relationship with the drug, include the following: neuroleptic malignant syndrome and Raynaud’s phenomenon.
# Drug Interactions
- Dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthines) or metoclopramide, ordinarily should not be administered concurrently with Pergolide (a dopamine agonist); these agents may diminish the effectiveness of Pergolide.
- Because pergolide is approximately 90% bound to plasma proteins, caution should be exercised if pergolide is coadministered with other drugs known to affect protein binding.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies were conducted in mice at doses of 5, 16, and 45 mg/kg/day and in rabbits at doses of 2, 6, and 16 mg/kg/day. The highest doses tested in mice and rabbits were 375 and 133 times the 6 mg/day maximum human dose administered in controlled clinical trials. In these studies, there was no evidence of harm to the fetus due to pergolide.
- There are, however, no adequate and well-controlled studies in pregnant women. Among women who received pergolide for endocrine disorders in premarketing studies, there were 33 pregnancies that resulted in healthy babies and 6 pregnancies that resulted in congenital abnormalities (3 major, 3 minor); a causal relationship has not been established. Because human data are limited and because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pergolide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Pergolide during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. The pharmacologic action of pergolide suggests that it may interfere with lactation. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions to pergolide in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- Of the total number of subjects in clinical studies of pergolide, 78 were 65 and over. There were no apparent differences in efficacy between these subjects and younger subjects. There was an increased incidence of confusion, somnolence, and peripheral edema in patients 65 and over. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
### Gender
There is no FDA guidance on the use of Pergolide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Pergolide with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Pergolide in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Pergolide in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pergolide in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Pergolide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Pergolide Administration in the drug label.
### Monitoring
There is limited information regarding Pergolide Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Pergolide and IV administrations.
# Overdosage
- There is no clinical experience with massive overdosage. The largest overdose involved a young hospitalized adult patient who was not being treated with pergolide but who intentionally took 60 mg of the drug. He experienced vomiting, hypotension, and agitation. Another patient receiving a daily dosage of 7 mg of pergolide unintentionally took 19 mg/day for 3 days, after which his vital signs were normal but he experienced severe hallucinations. Within 36 hours of resumption of the prescribed dosage level, the hallucinations stopped. One patient unintentionally took 14 mg/day for 23 days instead of her prescribed 1.4 mg/day dosage. She experienced severe involuntary movements and tingling in her arms and legs. Another patient who inadvertently received 7 mg instead of the prescribed 0.7 mg experienced palpitations, hypotension, and ventricular extrasystoles. The highest total daily dose (prescribed for several patients with refractory Parkinson's disease) has exceeded 30 mg.
- Symptoms— Animal studies indicate that the manifestations of overdosage in man might include nausea, vomiting, convulsions, hypotension, and CNS stimulation. The oral median lethal doses in mice and rats were 54 and 15 mg/kg respectively.
- Treatment— To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
- Management of overdosage may require supportive measures to maintain arterial blood pressure. Cardiac function should be monitored; an antiarrhythmic agent may be necessary. If signs of CNS stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdose has not been assessed.
- Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.
- There is no experience with dialysis or hemoperfusion, and these procedures are unlikely to be of benefit.
# Pharmacology
## Mechanism of Action
There is limited information regarding Pergolide Mechanism of Action in the drug label.
## Structure
- Pergolide mesylate is chemically designated as 8β-(Methylthio)methyl-6-propylergoline monomethanesulfonate; the structural formula is as follows:
The empirical formula is C19H26N2S∙CH4O3S, representing a molecular weight of 410.60.
## Pharmacodynamics
- Pergolide is a potent dopamine agonist. Pergolide is 10 to 1000 times more potent than bromocriptine on a milligram per milligram basis in various in vitro and in vivo test systems. Pergolide inhibits the secretion of prolactin in humans; it causes a transient rise in serum concentrations of growth hormone and a decrease in serum concentrations of luteinizing hormone. In Parkinson's disease, pergolide is believed to exert its therapeutic effect by directly stimulating postsynaptic dopamine receptors in the nigrostriatal system.
## Pharmacokinetics
- Information on oral systemic bioavailability of pergolide is unavailable because of the lack of a sufficiently sensitive assay to detect the drug after the administration of a single dose. However, following oral administration of 14C radiolabeled pergolide, approximately 55% of the administered radioactivity can be recovered from the urine and 5% from expired CO2, suggesting that a significant fraction is absorbed. Nothing can be concluded about the extent of presystemic clearance, if any.
- Pergolide is approximately 90% bound to plasma proteins. This extent of protein binding may be important to consider when pergolide is coadministered with other drugs known to affect protein binding.
- Data on postabsorption distribution of pergolide are unavailable.
- At least 10 metabolites have been detected, including N-despropylpergolide, pergolide sulfoxide, and pergolide sulfone.
- Pergolide sulfoxide and pergolide sulfone are dopamine agonists in animals. The other detected metabolites have not been identified and it is not known whether any other metabolites are active pharmacologically.
- The major route of excretion is the kidney.
## Nonclinical Toxicology
- A 2-year carcinogenicity study was conducted in mice using dietary levels of pergolide equivalent to oral doses of 0.6, 3.7, and 36.4 mg/kg/day in males and 0.6, 4.4, and 40.8 mg/kg/day in females. A 2-year study in rats was conducted using dietary levels equivalent to oral doses of 0.04, 0.18, and 0.88 mg/kg/day in males and 0.05, 0.28, and 1.42 mg/kg/day in females. The highest doses tested in the mice and rats were approximately 340 and 12 times the maximum human oral dose administered in controlled clinical trials (6 mg/day equivalent to 0.12 mg/kg/day).
- A low incidence of uterine neoplasms occurred in both rats and mice. Endometrial adenomas and carcinomas were observed in rats. Endometrial sarcomas were observed in mice. The occurrence of these neoplasms is probably attributable to the high estrogen/progesterone ratio that would occur in rodents as a result of the prolactin-inhibiting action of pergolide. The endocrine mechanisms believed to be involved in the rodents are not present in humans. However, even though there is no known correlation between uterine malignancies occurring in pergolide-treated rodents and human risk, there are no human data to substantiate this conclusion.
- Pergolide was evaluated for mutagenic potential in a battery of tests that included an Ames bacterial mutation assay, a DNA repair assay in cultured rat hepatocytes, an in vitro mammalian cell gene mutation assay in cultured L5178Y cells, and a determination of chromosome alteration in bone marrow cells of Chinese hamsters. A weak mutagenic response was noted in the mammalian cell gene mutation assay only after metabolic activation with rat liver microsomes. No mutagenic effects were obtained in the 2 other in vitro assays and in the in vivo assay. The relevance of these findings in humans is unknown.
- A fertility study in male and female mice showed that fertility was maintained at 0.6 and 1.7 mg/kg/day but decreased at 5.6 mg/kg/day. Prolactin has been reported to be involved in stimulating and maintaining progesterone levels required for implantation in mice and, therefore, the impaired fertility at the high dose may have occurred because of depressed prolactin levels.
# Clinical Studies
There is limited information regarding Pergolide Clinical Studies in the drug label.
# How Supplied
Tablets (modified rectangle shape, scored):
- 0.05 mg, ivory, debossed with A 024, in bottles of 30 (UC5336) — NDC 0187-0839-01
- 0.25 mg, green, debossed with A 025, in bottles of 100 (UC5337) — NDC 0187-0840-02
- 1 mg, pink, debossed with A 026, in bottles of 100 (UC5338) — NDC 0187-0841-02
## Storage
- Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F)
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Pergolide Patient Counseling Information in the drug label.
# Precautions with Alcohol
- Alcohol-Pergolide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Permax
# Look-Alike Drug Names
There is limited information regarding Pergolide Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Pergolide | |
f7c5a57d6acc1453c2c4ee0f78aa1b976a264f45 | wikidoc | Periodate | Periodate
The periodate ion is IO4− or IO65−. It comes from periodic acid.
A periodate is a compound that contains this group. Note that the pronunciation is per-iodate, not period-ate.
# Examples
- sodium periodate, NaIO4
- potassium periodate, KIO4
See category for a bigger list.
# Discussion
Periodates include two forms. The metaperiodate ion is IO4−; the orthoperiodate ion is IO65−.
Periodate compounds include metaperiodates and orthoperiodates. Usually both are called periodates.
In neutral or weak acid conditions, IO4− is most common, in equilibrium with a smaller amount of H4IO6−. In basic conditions, H3IO62− is formed, plus some other ions.
Like its neighbor, tellurium, and unlike lighter halogens, iodine tends to be hexacoordinate, and the units HnIO6(5−n)- are quite common; but in the case of iodine, tetracoordinate units, such as IO4−, are also quite common.
# Uses
Periodates can cleave carbon-carbon bonds when both carbon atoms bear an oxygen atom, either in the form of a hydroxyl or a carbonyl group. This property is often utilized in molecular biochemistry for the purposes of modifying saccharide rings, as many five- and six-membered sugars often have vicinal diols. | Periodate
The periodate ion is IO4− or IO65−. It comes from periodic acid.
A periodate is a compound that contains this group. Note that the pronunciation is per-iodate, not period-ate.
# Examples
- sodium periodate, NaIO4
- potassium periodate, KIO4
See category for a bigger list.
# Discussion
Periodates include two forms. The metaperiodate ion is IO4−; the orthoperiodate ion is IO65−.
Periodate compounds include metaperiodates and orthoperiodates. Usually both are called periodates.
In neutral or weak acid conditions, IO4− is most common, in equilibrium with a smaller amount of H4IO6−. In basic conditions, H3IO62− is formed, plus some other ions.
Like its neighbor, tellurium, and unlike lighter halogens, iodine tends to be hexacoordinate, and the units HnIO6(5−n)- are quite common; but in the case of iodine, tetracoordinate units, such as IO4−, are also quite common.
# Uses
Periodates can cleave carbon-carbon bonds when both carbon atoms bear an oxygen atom, either in the form of a hydroxyl or a carbonyl group. This property is often utilized in molecular biochemistry for the purposes of modifying saccharide rings, as many five- and six-membered sugars often have vicinal diols.
Template:Chem-stub | https://www.wikidoc.org/index.php/Periodate | |
635ff61c12e7743a1d8b6f74d8f0caf14d2ee4f1 | wikidoc | Periostin | Periostin
Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells.
Periostin is a gla domain vitamin K dependent factor.
# Function
Periostin is a secreted extracellular matrix protein that was originally identified in cells from the mesenchymal lineage (osteoblasts, osteoblast-derived cells, the periodontal ligament, and periosteum). It has been associated with the epithelial-mesenchymal transition in cancer and with the differentiation of mesenchyme in the developing heart. This protein shares a homology with fasciclin I, a secreted cell adhesion molecule found in insects.
In many cancers, periostin binds to integrins on cancer cells, activating the Akt/PKB- and FAK-mediated signaling pathways. This leads to increased cell survival, invasion, angiogenesis, metastasis, and the epithelial-mesenchymal transition.
In humans and mice, periostin undergoes alternative splicing in its C-terminal region, resulting in specific isoforms that can be observed in a broad range of cancers such as pancreatic, colon, and breast cancer.
While periostin plays a wide variety of roles in tissue development along with disease, its function in tissue remodeling as a response to injury is a common underlying role in these different mechanisms. Periostin is transiently upregulated during cell fate changes, whether they are related to alterations in physiology or to pathological changes. It influences extracellular matrix restructuring, tissue remodeling, and the epithelial-mesenchymal transition, all of which can be related to tissue healing, development, and disease. Thus, it functions as a mediator, balancing appropriate and inappropriate responses to tissue damage.
# Clinical significance
## In valvular heart disease
Periostin plays a critical role in the development of cardiac valves and in degenerative valvular heart disease. While periostin usually is localized to the subendothelial layer in healthy heart valves, its levels are highly increased in infiltrated inflammatory cells and myofibroblasts in angiogenic areas in atherosclerotic and rheumatic valvular heart disease in humans. Periostin has also been shown to increase the secretion of matrix metalloproteinase from valvular intestinal cells, endothelial cells, and macrophages. It is thought that periostin plays a role in cardiac valve complex degeneration by inducing both angiogenesis and matrix metalloproteinase production.
## In tissue regeneration and healing
As a matricellular protein, periostin is also important for tissue regeneration. In healthy human skin, periostin is expressed at basal levels and is expressed in the epidermis and hair follicles along with fibronectin and laminin γ2. Periostin is involved in wound healing, helping for the wound to heal faster than when periostin is not present in cells. This delay in wound closure is also associated with a delay in re-epithelialization and a reduction in the proliferation of keratinocytes. Periostin localizes to the extracellular compartment of cells during tissue remodeling associated with wound repair. It may also promote injury closure by facilitating the activation, differentiation, and contraction of fibroblasts. However, the increase in periostin expression associated with tissue regeneration post-injury is transient, starting a few days post-injury, peaking after seven days post-injury, and decreasing afterwards.
## In asthma
Periostin is associated with asthma, a fact that is exploited by the experimental asthma medication lebrikizumab.
## In cancer
Periostin over-expression was reported in several types of cancer, most frequently in the environment of tumor cells. Recent evidence shows that periostin is a component of the extracellular matrix expressed by fibroblasts in normal tissues and stroma of primary tumor. The metastatic colony formation requires the induction of periostin in the foreign stroma by the infiltrating cancer cells. Periostin production is upregulated in lung fibroblasts by either TGF-β2 or TGF-β3, the latter being secreted by infiltrating cancer stem cells (in MMTV-PyMT mouse breast cancer model)
Periostin has been shown to be highly upregulated in glioblastomas (grade IV gliomas) compared to the normal brain. In gliomas, periostin expression levels correlate directly with tumor grade and recurrence, and inversely with survival. It has been shown that glioma stem cells in glioblastomas secrete periostin, which recruits M2 tumor-associated macrophages from peripheral blood to the tumor environment via αvβ3 integrin signaling. These M2 TAMs differentiate from monocytes once they enter the tumor tissue. Through this recruitment mechanism, periostin supports tumor progression, as M2 tumor-associated macrophages are tumor-supportive and immunosuppressive. In this environment, periostin functions as a chemoattractant, promoting both migration and invasion of macrophages and monocytes into glioblastomas in a dose-dependent manner. Clinically, periostin-associated gene signatures, which are predominated by secreted and matrix proteins, correspond to patient prognosis and malignancy. Given its features related to glioblastoma progression, periostin is a marker of glioma malignancy as well as recurrence of tumors, making it a possible target for therapy that continues to be studied and explored.
1 (cDNA POSTN/cDNA ACTB) × 104 | Periostin
Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene.[1][2] Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells.[3]
Periostin is a gla domain vitamin K dependent factor.[4]
# Function
Periostin is a secreted extracellular matrix protein that was originally identified in cells from the mesenchymal lineage (osteoblasts, osteoblast-derived cells, the periodontal ligament, and periosteum). It has been associated with the epithelial-mesenchymal transition in cancer and with the differentiation of mesenchyme in the developing heart.[5] This protein shares a homology with fasciclin I, a secreted cell adhesion molecule found in insects.
In many cancers, periostin binds to integrins on cancer cells, activating the Akt/PKB- and FAK-mediated signaling pathways. This leads to increased cell survival, invasion, angiogenesis, metastasis, and the epithelial-mesenchymal transition.[6]
In humans and mice, periostin undergoes alternative splicing in its C-terminal region, resulting in specific isoforms that can be observed in a broad range of cancers such as pancreatic, colon, and breast cancer.[5]
While periostin plays a wide variety of roles in tissue development along with disease, its function in tissue remodeling as a response to injury is a common underlying role in these different mechanisms. Periostin is transiently upregulated during cell fate changes, whether they are related to alterations in physiology or to pathological changes. It influences extracellular matrix restructuring, tissue remodeling, and the epithelial-mesenchymal transition, all of which can be related to tissue healing, development, and disease. Thus, it functions as a mediator, balancing appropriate and inappropriate responses to tissue damage.[7]
# Clinical significance
## In valvular heart disease
Periostin plays a critical role in the development of cardiac valves and in degenerative valvular heart disease. While periostin usually is localized to the subendothelial layer in healthy heart valves, its levels are highly increased in infiltrated inflammatory cells and myofibroblasts in angiogenic areas in atherosclerotic and rheumatic valvular heart disease in humans. Periostin has also been shown to increase the secretion of matrix metalloproteinase from valvular intestinal cells, endothelial cells, and macrophages. It is thought that periostin plays a role in cardiac valve complex degeneration by inducing both angiogenesis and matrix metalloproteinase production.[8]
## In tissue regeneration and healing
As a matricellular protein, periostin is also important for tissue regeneration. In healthy human skin, periostin is expressed at basal levels and is expressed in the epidermis and hair follicles along with fibronectin and laminin γ2.[7][9] Periostin is involved in wound healing, helping for the wound to heal faster than when periostin is not present in cells. This delay in wound closure is also associated with a delay in re-epithelialization and a reduction in the proliferation of keratinocytes.[9] Periostin localizes to the extracellular compartment of cells during tissue remodeling associated with wound repair. It may also promote injury closure by facilitating the activation, differentiation, and contraction of fibroblasts. However, the increase in periostin expression associated with tissue regeneration post-injury is transient, starting a few days post-injury, peaking after seven days post-injury, and decreasing afterwards.[7]
## In asthma
Periostin is associated with asthma, a fact that is exploited by the experimental asthma medication lebrikizumab.[10]
## In cancer
Periostin over-expression was reported in several types of cancer, most frequently in the environment of tumor cells.[3][11] Recent evidence shows that periostin is a component of the extracellular matrix expressed by fibroblasts in normal tissues and stroma of primary tumor. The metastatic colony formation requires the induction of periostin in the foreign stroma by the infiltrating cancer cells. Periostin production is upregulated in lung fibroblasts by either TGF-β2 or TGF-β3, the latter being secreted by infiltrating cancer stem cells (in MMTV-PyMT mouse breast cancer model) [12]
Periostin has been shown to be highly upregulated in glioblastomas (grade IV gliomas) compared to the normal brain. In gliomas, periostin expression levels correlate directly with tumor grade and recurrence, and inversely with survival.[13] It has been shown that glioma stem cells in glioblastomas secrete periostin, which recruits M2 tumor-associated macrophages from peripheral blood to the tumor environment via αvβ3 integrin signaling. These M2 TAMs differentiate from monocytes once they enter the tumor tissue. Through this recruitment mechanism, periostin supports tumor progression, as M2 tumor-associated macrophages are tumor-supportive and immunosuppressive. In this environment, periostin functions as a chemoattractant, promoting both migration and invasion of macrophages and monocytes into glioblastomas in a dose-dependent manner.[14] Clinically, periostin-associated gene signatures, which are predominated by secreted and matrix proteins, correspond to patient prognosis and malignancy. Given its features related to glioblastoma progression, periostin is a marker of glioma malignancy as well as recurrence of tumors, making it a possible target for therapy that continues to be studied and explored.[13]
1 (cDNA POSTN/cDNA ACTB) × 104 | https://www.wikidoc.org/index.php/Periostin | |
0747af1b0e02c531a8edd11b3649cccb44dfe819 | wikidoc | Periphery | Periphery
Generally, a periphery is a boundary or outer part of any space or body. It is derived from the Greek word περιφέρεια, meaning a circumference or outer surface.
- In biology, the periphery of the body is the part that is away from the central or core regions.
For example, the peripheral nervous system is distinct from the central nervous system.
See also peripheral membrane protein.
- For example, the peripheral nervous system is distinct from the central nervous system.
- See also peripheral membrane protein.
- Peripheral vision is that part of visual perception that occurs in the periphery, i.e., near the edges, of the field of view.
- A computer peripheral is added to a host computer in order to expand its abilities.
- For peripheral submanifolds in mathematics, see boundary parallel.
- Periphery countries includes nations that are not core countries - capitalist or industrialized nations. See Immanuel Wallerstein, Third World.
- The 13 peripheries of Greece are subnational subdivisions of that country, equivalent to regions.
- In the fictional universe of BattleTech, the Periphery is the region of interstellar space.
- In Issac Asimov's Foundation Series, the Periphery is that part of the Empire that lies on the very edge of the Milky Way Galaxy. The Foundation, located on the planet Terminus lies in the Periphery, in the ancient imperial provence of Anacreon.
- Periphery also refers to the boundary of a town or city, also known as outskirts or suburbs ; it also refers to what is not mainstream or central.
de:Peripherie
simple:Peripheral (disambiguation) | Periphery
Generally, a periphery is a boundary or outer part of any space or body. It is derived from the Greek word περιφέρεια, meaning a circumference or outer surface.
- In biology, the periphery of the body is the part that is away from the central or core regions.
For example, the peripheral nervous system is distinct from the central nervous system.
See also peripheral membrane protein.
- For example, the peripheral nervous system is distinct from the central nervous system.
- See also peripheral membrane protein.
- Peripheral vision is that part of visual perception that occurs in the periphery, i.e., near the edges, of the field of view.
- A computer peripheral is added to a host computer in order to expand its abilities.
- For peripheral submanifolds in mathematics, see boundary parallel.
- Periphery countries includes nations that are not core countries - capitalist or industrialized nations. See Immanuel Wallerstein, Third World.
- The 13 peripheries of Greece are subnational subdivisions of that country, equivalent to regions.
- In the fictional universe of BattleTech, the Periphery is the region of interstellar space.
- In Issac Asimov's Foundation Series, the Periphery is that part of the Empire that lies on the very edge of the Milky Way Galaxy. The Foundation, located on the planet Terminus lies in the Periphery, in the ancient imperial provence of Anacreon.
- Periphery also refers to the boundary of a town or city, also known as outskirts or suburbs ; it also refers to what is not mainstream or central.
de:Peripherie
simple:Peripheral (disambiguation)
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Periphery | |
9d81f3d7005740f5a8e5d1f3cb23e99ef10d4774 | wikidoc | Pesticide | Pesticide
# Overview
The U.S Environmental Protection Agency (EPA) defines a pesticide as "any substance or mixture of substances intended for preventing, destroying, repelling, or lessening the damage of any pest".
A pesticide may be a chemical substance, biological agent (such as a virus or bacteria), antimicrobial, disinfectant or device used against any pest. Pests include insects, plant pathogens, weeds, mollusks, birds, mammals, fish, nematodes (roundworms) and microbes that compete with humans for food, destroy property, spread or are a vector for disease or are a nuisance. Many pesticides are poisonous to humans.
# Types of Pesticides
There are multiple ways of classifying pesticides.
- Bactericides for the control of bacteria
- Fungicides for the control of fungi and oomycetes
- Herbicides for the control of weeds
- Insecticides for the control of insects - these can be Ovicides (substances that kill eggs), Larvicides (substances that kill larvae) or Adulticides (substances that kill adult insects)
- Miticides for the control of mites
- Molluscicides for the control of slugs and snails
- Nematicides for the control of nematodes
- Rodenticides for the control of rodents
- Virucides for the control of viruses (e.g. H5N1)
Pesticides can also be classed as synthetic pesticides or biological pesticides, although the distinction can sometimes blur.
Broad-spectrum pesticides are those that kill an array of species, while narrow-spectrum, or selective pesticides only kill a small group of species.
A systemic pesticide moves inside a plant following absorption by the plant. This movement is usually upward (through the xylem) and outward. Increased efficiency may be a result. Systemic insecticides which poison pollen and nectar in the flowers may kill needed pollinators such as bees.
Most pesticides work by poisoning pests.
# Uses and benefits
Pesticides are used to control organisms which are considered harmful. For example, they are used to kill mosquitoes that can transmit potentially deadly diseases like west nile virus and malaria. They can also kill bees, wasps or ants that can cause allergic reactions. Insecticides can protect animals, because infestations by parasites such as fleas may cause them illness. Pesticides can prevent sickness in humans that could be caused by moldy food or diseased produce. Herbicides can prevent accidents by clearing roadside trees and brush, which may block visibility. They can also kill invasive weeds in parks and wilderness areas which may cause environmental damage. Herbicides are commonly applied in ponds and lakes to control algae and plants such as water grasses that can interfere with activities like swimming and fishing and cause the water to look or smell unpleasant. Uncontrolled pests such as termites and mold can damage structures such as houses. Pesticides are used in grocery stores and food storage facilities to manage rodents and insects that infest food such as grain. Each use of a pesticide carries some associated risk. Proper pesticide use decreases these associated risks to a level deemed acceptable and increases quality of life and protects property and the environment.
Pesticides save farmers money by preventing crop losses to insects and other pests; in the US, farmers get an estimated four-fold return on money they spend on pesticides.
In 2006, the World Health Organization suggested the resumption of the limited use of DDT to fight malaria. They called for the use of DDT to coat the inside walls of houses in areas where mosquitoes are prevalent. Dr. Arata Kochi, WHO's malaria chief, said, "One of the best tools we have against malaria is indoor residual house spraying. Of the dozen insecticides WHO has approved as safe for house spraying, the most effective is DDT." Scientists estimate that DDT and other chemicals in the organophosphate class of pesticides have saved 7 million human lives since 1945 by preventing the transmission of diseases such as malaria, bubonic plague, sleeping sickness, and typhus.
In the US, about a quarter of pesticides used are used in houses, yards, parks, golf courses, and swimming pools. About 70% of the pesticides sold in the US are used in agriculture.
# History
Since before 2500 BC, humans have used pesticides to prevent damage to their crops. The first known pesticide was elemental sulfur dusting used in Sumeria about 4,500 years ago. By the 15th century, toxic chemicals such as arsenic, mercury and lead were being applied to crops to kill pests. In the 17th century, nicotine sulfate was extracted from tobacco leaves for use as an insecticide. The 19th century saw the introduction of two more natural pesticides, pyrethrum which is derived from chrysanthemums, and rotenone which is derived from the roots of tropical vegetables.
In 1939, Paul Müller discovered that DDT was a very effective insecticide. It quickly became the most widely-used pesticide in the world. However, in the 1960s, it was discovered that DDT was preventing many fish-eating birds from reproducing which was a huge threat to biodiversity. Rachel Carson wrote the best-selling book Silent Spring about biological magnification. DDT is now banned in at least 86 countries, but it is still used in some developing nations to prevent malaria and other tropical diseases by killing mosquitoes and other disease-carrying insects.
In the 1940s manufacturers began to produce large amounts of synthetic pesticides and their use became widespread. Some sources consider the 1940s and 1950s to have been the start of the "pesticide era." Pesticide use has increased 50-fold since 1950 and 2.5 million tons (2.3 million metric tons) of industrial pesticides are now used each year. Seventy-five percent of all pesticides in the world are used in developed countries, but use in developing countries is increasing.
# Regulation
In most countries, in order to sell or use a pesticide, it must be approved by a government agency. For example, in the United States, the Environmental Protection Agency (EPA) does so. Complex and costly studies must be conducted to indicate whether the material is safe to use and effective against the intended pest. During the registration process, a label is created which contains directions for the proper use of the material. Based on acute toxicity, pesticides are assigned to a Toxicity Class. Intentional pesticide misuse is illegal worldwide.
Some pesticides are considered too hazardous for sale to the general public and are designated restricted use pesticides. Only certified applicators, who have passed an exam, may purchase or supervise the application of restricted use pesticides. Records of sales and use are required to be maintained and may be audited by government agencies charged with the enforcement of pesticide regulations.
"Read and follow label directions" is a phrase often quoted by extension agents, garden columnists and others teaching about pesticides. This is required by law in countries such as the US. Similar laws exist in limited parts of the rest of the world. In the US, the Federal Insecticide, Fungicide, and Rodenticide Act of 1972 (FIFRA) set up the current system of pesticide regulations. It was amended somewhat by the Food Quality Protection Act of 1996. Its purpose is to make pesticide manufacture, distribution and use as safe as possible. The most important points for users to understand are these: it is a violation to apply any pesticide in a manner not in accordance with the label for that pesticide, and it is a crime to do so intentionally.
# Environmental effects
Use of pesticides can have unintended effects on the environment. Over 98% of sprayed insecticides and 95% of herbicides reach a destination other than their target species, including nontarget species, air, water, bottom sediments, and food. Pesticide contaminates land and water when it escapes from production sites and storage tanks, when it runs off from fields, when it is discarded, when it is sprayed aerially, and when it is sprayed into water to kill algae. The amount of pesticide that migrates from the intended application area is influenced by the particular chemical's properties: its propensity for binding to soil, its vapor pressure, its water solubility, and its resistance to being broken down over time. Factors in the soil, such as its texture, its ability to retain water, and the amount of organic matter contained in it, also affect the amount of pesticide that will leave the area.
## Air
Pesticides can contribute to air pollution. Pesticide drift occurs when pesticides suspended in the air as particles are carried by wind to other areas, potentially contaminating them. Pesticides that are applied to crops can volatilize and may be blown by winds into nearby areas, potentially posing a threat to wildlife. Also, droplets of sprayed pesticides or particles from pesticides applied as dusts may travel on the wind to other areas, or pesticides may adhere to particles that blow in the wind, such as dust particles. Ground spraying produces less pesticide drift than aerial spraying does. Farmers can employ a buffer zone around their crop, consisting of empty land or non-crop plants such as evergreen trees to serve as windbreaks and absorb the pesticides, preventing drift into other areas. Such windbreaks are legally required in the Netherlands.
Pesticides that are sprayed onto fields and used to fumigate soil can give off chemicals called volatile organic compounds, which can react with other chemicals and form a pollutant called ozone, accounting for an estimated 6% of the total ozone production.
## Water
In the United States, pesticides were found to pollute every stream and over 90% of wells sampled in a study by the US Geological Survey. Pesticide residues have also been found in rain and groundwater. Studies by the UK government showed that pesticide concentrations exceeded those allowable for drinking water in some samples of river water and groundwater.
Pesticide impacts on aquatic systems are often studied using a hydrology transport model to study movement and fate of chemicals in rivers and streams. As early as the 1970s quantitative analysis of pesticide runoff was conducted in order to predict amounts of pesticide that would reach surface waters.
There are four major routes through which pesticides reach the water: it may drift outside of the intended area when it is sprayed, it may percolate, or leach, through the soil, it may be carried to the water as runoff, or it may be spilled, for example accidentally or through neglect. They may also be carried to water by eroding soil. Factors that affect a pesticide's ability to contaminate water include its water solubility, the distance from an application site to a body of water, weather, soil type, presence of a growing crop, and the method used to apply the chemical.
In the US, the Environmental Protection Agency sets Maximum Contamination Levels, or maximum allowable concentrations for individual pesticides in public bodies of water.
Similarly, the government of the United Kingdom sets Environmental Quality Standards (EQS), or maximum allowable concentrations of some pesticides in bodies of water above which toxicity may occur. The European Union also regulates maximum concentrations of pesticides in water.
## Soil
Many of the chemicals used in pesticides are persistent soil contaminants, whose impact may endure for decades and adversely affect soil conservation.
The use of pesticides decreases the general biodiversity in the soil. Not using the chemicals results in higher soil quality, with the additional effect that more organic matter in the soil allows for higher water retention. This helps increase yields for farms in drought years, when organic farms have had yields 20-40% higher than their conventional counterparts. A smaller content of organic matter in the soil increases the amount of pesticide that will leave the area of application, because organic matter binds to and helps break down pesticides.
## Plants
Nitrogen fixation, which is required for the growth of higher plants, is hindered by pesticides in soil. The insecticides DDT, methyl parathion, and especially pentachlorophenol have been shown to interfere with legume-rhizobium chemical signaling. Reduction of this symbiotic chemical signaling results in reduced nitrogen fixation and thus reduced crop yields. Root nodule formation in these plants saves the world economy $10 billion in synthetic nitrogen fertiliser every year.
Pesticides can kill bees and are strongly implicated in pollinator decline, the loss of species that polinate plants, including through the mechanism of Colony Collapse Disorder, in which worker bees from a beehive or Western honey bee colony abruptly disappear. Application of pesticides to crops that are in bloom can kill honeybees, which act as pollinators. The USDA and USFWS estimate that US farmers lose at least $200 million a year from reduced crop pollination because pesticides applied to fields eliminate about a fifth of honeybee colonies in the US and harm an additional 15%.
## Persistent organic pollutants
Persistent organic pollutants (POPs) are compounds that resist degradation and thus remain in the environment for years. Some pesticides, including aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and toxaphene, are considered POPs. POPs have the ability to volatilize and travel great distances through the atmosphere to become deposited in remote regions. The chemicals also have the ability to bioaccumulate and biomagnify, and can bioconcentrate (i.e. become more concentrated) up to 70,000 times their original concentrations. POPs may continue to poison non-target organisms in the environment and increase risk to humans by disruption in the endocrine, reproductive, and immune systems; cancer; neurobehavioral disorders, infertility and mutagenic effects, although very little is currently known about these chronic effects. Some POPs have been banned, while others continue to be used.
## Animals
Pesticides inflict extremely widespread damage to biota, and many countries have acted to discourage pesticide usage through their Biodiversity Action Plans.
Animals may be poisoned by pesticide residues that remain on food after spraying, for example when wild animals enter sprayed fields or nearby areas shortly after spraying.
Widespread application of pesticides can eliminate food sources that certain types of animals need, causing the animals to relocate, change their diet, or starve. Poisoning from pesticides can travel up the food chain; for example, birds can be harmed when they eat insects and worms that have consumed pesticides. Some pesticides can bioaccumulate, or build up to toxic levels in the bodies of organisms that consume them over time, a phenomenon that impacts species high on the food chain especially hard.
The USDA and USFWS estimate that about 20% of the endangered and threatened species in the US are jeopardized by use of pesticides.
### Birds
Birds are common examples of nontarget organisms that are impacted by pesticide use. Rachel Carson's landmark book Silent Spring dealt with the topic of loss of bird species due to bioaccumulation of pesticides in their tissues. There is evidence that birds are continuing to be harmed by pesticide use. In the farmland of Britain, populations of ten different species of birds have declined by 10 million breeding individuals between 1979 and 1999, a phenomenon thought to have resulted from loss of plant and invertebrate species on which the birds feed. Throughout Europe, 116 species of birds are now threatened. Reductions in bird populations have been found to be associated with times and areas in which pesticides are used. In another example, some types of fungicides used in peanut farming are only slightly toxic to birds and mammals, but may kill off earthworms, which can in turn reduce populations of the birds and mammals that feed on them.
Some pesticides come in granular form, and birds an other wildlife may eat the granules, mistaking them for grains of food. A few granules of a pesticide is enough to kill a small bird.
The herbicide paraquat, when sprayed onto bird eggs, causes growth abnormalities in embryos and reduces the number of chicks that hatch successfully, but most herbicides do not directly cause much harm to birds. Herbicides may endanger bird populations by reducing their habitat.
The USDA and USFWS estimate that over 67 million birds are killed by pesticides each year in the US.
### Aquatic life
Fish and other aquatic biota may be harmed by pesticide-contaminated water. Pesticide surface runoff into rivers and streams can be highly lethal to aquatic life, sometimes killing all the fish in a particular stream. For example, in Montague P.E.I., nine "fish kills" happened in one year: every fish, snake, and snail was killed in a river called Sutherland's Hole near potato farms from which herbicides, insecticides, and fungicides ran off after heavy rains. Pesticide-related fish kills are frequently unreported and likely underestimated.
Application of herbicides to bodies of water can cause fish kills when the dead plants rot and use up the water's oxygen, suffocating the fish. Some herbicides, such as copper sulfite, that are applied to water to kill plants are toxic to fish and other water animals at concentrations similar to those used to kill the plants.
Pesticides can accumulate in bodies of water to levels that kill off zooplankton, the main source of food for young fish.
The USDA and USFWS estimate that between 6 and 14 million fish are killed by pesticides each year in the US.
The faster a given pesticide breaks down in the environment, the less threat it poses to aquatic life. Insecticides are more toxic to aquatic life than herbicides and fungicides.
### Amphibians
Some scientists believe that certain common pesticides already exist at levels capable of killing amphibians in California. They warn that the breakdown products of these pesticides can be 10 to 100 times more toxic to amphibians than the original pesticides. Direct contact of sprays of some pesticides (either by drift from nearby applications or accidental or deliberate sprays) can be highly lethal to amphibians.
US scientists have found that some pesticides used in farming disrupt the nervous systems of frogs, and that use of these pesticides is correlated with a decline in the population of frogs in the Sierra Nevada. In the past several decades, decline in amphibian populations has been occurring all over the world, for unexplained reasons which are thought to be varied but of which pesticides may be a part. Being downwind from agricultural land on which pesticides are used has been linked to the decline in population of threatened frog species in California.
In Minnesota, pesticide use has been causally linked to congenital deformities in frogs such as eye, mouth, and limb malformations. Researchers in California found that similar deformities in frogs in the US and Canada may have been caused by breakdown products from pesticides which themselves did not pose a threat.
## Pest resistance
An early discovery relating to pesticide use is that pests may eventually evolve to become resistant to chemicals. When sprayed with pesticides, many pests will initially be very susceptible. However, not all pests are killed, and some with slight variations in their genetic makeup are resistant and therefore survive. Through natural selection, the pests may eventually become very resistant to the pesticide.
Pest resistance to a pesticide is commonly managed through pesticide rotation, which involves alternating among pesticide classes with different modes of action to delay the onset of or mitigate existing pest resistance.
Tankmixing pesticides is the combination of two or more pesticides with different modes of action in order to improve individual pesticide application results and delay the onset of or mitigate existing pest resistance.
## Pest rebound and secondary pest outbreaks
Non-target organisms, organisms that the pesticides are not intended to kill, can be severely impacted by use of the chemicals. In some cases, where a pest insect has some controls from a beneficial predator or parasite, an insecticide application can kill both pest and beneficial populations. A study comparing biological pest control and use of pyrethroid insecticide for diamondback moths, a major cabbage family insect pest, showed that the insecticide application created a rebounded pest population due to loss of insect predators, whereas the biocontrol did not show the same effect. Likewise, pesticides sprayed in an effort to control adult mosquitoes, may temporarily depress mosquito populations, however they may result in a larger population in the long run by damaging the natural controlling factors. This phenomenon, wherein the population of a pest species rebounds to equal or greater numbers than it had before pesticide use, is called pest resurgence and can be linked to elimination of predators and other natural enemies of the pest.
Loss of predator species can also lead to a related phenomenon called secondary pest outbreaks, an increase in problems from species which were not originally very damaging pests due to loss of their predators or parasites. An estimated third of the 300 most damaging insects in the US were originally secondary pests and only became a major problem after the use of pesticides. In both pest resurgence and secondary pest outbreaks, the natural enemies have been found to be more susceptible to the pesticides than the pests themselves, in some cases causing the pest population to be higher than it was before the use of pesticide.
# Health effects
Pesticides can present danger to consumers, bystanders, or workers during manufacture, transport, or during and after use.
## Farmers
There have been many studies of farmers with the goal of determining the health effects of pesticide exposure.
The World Health Organization and the UN Environment Programme estimate that each year, 3 million workers in agriculture in the developing world experience severe poisoning from pesticides, about 18,000 of whom die.
Research in Bangladesh suggests that many farmers do not need to apply pesticide to their rice fields, but continue to do so only because the pesticide is paid for by the government. Organophosphate pesticides have increased in use, because they are less damaging to the environment and they are less persistent than organochlorine pesticides. These are associated with acute health problems such as abdominal pain, dizziness, headaches, nausea, vomiting, as well as skin and eye problems. Additionally, many studies have indicated that pesticide exposure is associated with long-term health problems such as respiratory problems, memory disorders, dermatologic conditions, cancer, depression, neurologic deficits, miscarriages, and birth defects. Summaries of peer-reviewed research have examined the link between pesticide exposure and neurologic outcomes and cancer, perhaps the two most significant things resulting in organophosphate-exposed workers.
## Consumers
There is concern that pesticides used to control pests on food crops are dangerous to people who consume those foods. These concerns are one reason for the organic food movement. Many food crops, including fruits and vegetables, contain pesticide residues after being washed or peeled (see Pesticide residues in food, below). In the US, levels of residues that remain on foods are limited to tolerance levels that are established by the US EPA and are considered safe. The EPA sets the tolerances based on the toxicity of the pesticide and its break-down products, the amount and frequency of pesticide application, and how much of the pesticide (i.e., the residue) remains in or on food by the time it is marketed and prepared. Tolerance levels are obtained using scientific risk assessments that pesticide manufacturers are required to produce by conducting toxicological studies, exposure modeling and residue studies before a particular pesticide can be registered, however, the effects are tested for single pesticides, and there is no information on possible synergistic effects of exposure to multiple pesticide traces in the air, food and water.
In the US, the National Academy of Sciences estimates that between 4,000 and 20,000 cases of cancer are caused per year by pesticide residues in food in allowable amounts.
A new study conducted by the Harvard School of Public Health in Boston, has discovered a 70% increase in the risk of developing Parkinson’s disease for people exposed to even low levels of pesticides.
A study published by the United States National Research Council in 1993 determined that for infants and children, the major source of exposure to pesticides is through diet. A study in 2006 measured the levels of organophosphorus pesticide exposure in 23 school children before and after replacing their diet with organic food (food grown without synthetic pesticides). In this study it was found that levels of organophosphorus pesticide exposure dropped dramatically and immediately when the children switched to an organic diet.
### Pesticide residues in food
The Pesticide Data Program, a program started by the United States Department of Agriculture is the largest tester of pesticide residues on food sold in the United States. It began in 1990, and has since tested over 60 different types of food for over 400 different types of pesticides - with samples collected close to the point of consumption. Their most recent summary results are from the year 2005:
For example, on page 30 is comprehensive data on pesticides on fruits. Some example data:
They were also able to test for multiple pesticides within a single sample and found that:
The Environmental Working Group used the results of nearly 43,000 tests for pesticides on produce collected by the USDA and the U.S. FDA between 2000 and 2004, to produce a ranking of 43 commonly eaten fruits & vegetables.
## The public
Exposure routes other than consuming food that contains residues, in particular pesticide drift, are potentially significant to the general public.
The Bhopal disaster occurred when a pesticide plant released 40 tons of methyl isocyanate (MIC) gas, intermediate chemical in the production of some pesticides. The disaster immediately killed nearly 3,000 people and ultimately caused at least 15,000 deaths.
Children have been found to be especially susceptible to the harmful effects of pesticides. A number of research studies have found higher instances of brain cancer, leukemia and birth defects in children with early exposure to pesticides, according to the Natural Resources Defense Council.
Peer-reviewed studies now suggest neurotoxic effects on developing animals from organophosphate pesticides at legally-tolerable levels, including fewer nerve cells, lower birth weights, and lower cognitive scores. The EPA finished a 10 year review of the organophosphate pesticides following the 1996 Food Quality Protection Act, but did little to account for developmental neurotoxic effects, drawing strong criticism from within the agency and from outside researchers.
Some scientists think that exposure to pesticides in the uterus may have negative effects on a fetus that may manifest as problems such as growth and behavioral disorders or reduced resistance to pesticide toxicity later in life.
One study found that use of pesticides may be behind the finding that the rate of birth defects such as missing or very small eyes is twice as high in rural areas as in urban areas. Another study found no connection between eye abnormalities and pesticides.
Pyrethrins, insecticides commonly used in common bug killers, can cause a potentially deadly condition if breathed in.
# Continuing development of pesticides
Pesticide safety education and pesticide applicator regulation are designed to protect the public from pesticide misuse, but do not eliminate all misuse. Reducing the use of pesticides and replacing high risk pesticides is a solution to reducing risks placed on our society from pesticide use. For over 30 years, there has been a trend in the United States and in many other parts of the world to use pesticides in combination with alternative pest controls. Integrated pest management, the use of multiple approaches to control pests, is becoming widespread and has been used with success in countries such as Indonesia, China, Bangladesh, the US, Australia, and Mexico. IPM attempts to recognize the more widespread impacts of an action on an ecosystem, so that natural balances are not upset. With pesticide regulations that now put a higher priority on reducing the risks of pesticides in the food supply and emphasize environmental protection, old pesticides are being phased out in favor of new reduced risk pesticides. These new pesticides include biological and botanical derivatives and alternatives that are thought to reduce health and environmental risks. Chemical engineers continually develop new pesticides to produce enhancements over previous generations of products. In addition, applicators are being encouraged to consider alternative controls and adopt methods that reduce the use of chemical pesticides. This process is ongoing and is not an immediate solution to the risks of pesticide use.
Pesticides can be created that are targeted to a specific pest's life cycle, which can be more environmentally-friendly. For example, potato cyst nematodes emerge from their protective cysts in response to a chemical excreted by potatoes; they feed on the potatoes and damage the crop. A similar chemical can be applied to fields early, before the potatoes are planted, causing the nematodes to emerge early and starve in the absence of potatoes.
# Alternatives
Alternatives to pesticides are available and include methods of cultivation, use of other organisms to kill pests, genetic engineering, and interfering with insect breeding.
Cultivation practices include polyculture (growing multiple types of plants), crop rotation, planting crops in areas where the pests that damage them do not live, timing planting according to when pests will be least problematic, use of trap crops that attract pests away from the real crop. In the US, farmers have had success controlling insects by spraying with hot water at a cost that is about the same as pesticide spraying.
Release of other organisms that fight the pest is another example of an alternative to pesticide use. These organisms can include natural predators or parasites of the pests. Pathogens such as bacteria and viruses which cause disease in the pest species can also be used.
Interfering with insects' reproduction can be accomplished by sterilizing males of the target species and releasing them, so that they mate with females but do not produce offspring. This technique was first used on the screwworm fly in 1958 and has since been used with the medfly, the tsetse fly, and the gypsy moth. However, this can be a costly, time consuming approach that only works on some types of insects.
Some evidence shows that alternatives to pesticides can be equally effective as the use of chemicals. For example, Sweden has halved its use of pesticides with hardly any reduction in crops. In Indonesia, farmers have reduced pesticide use on rice fields by 65% and experienced a 15% crop increase. | Pesticide
# Overview
The U.S Environmental Protection Agency (EPA) defines a pesticide as "any substance or mixture of substances intended for preventing, destroying, repelling, or lessening the damage of any pest".[1]
A pesticide may be a chemical substance, biological agent (such as a virus or bacteria), antimicrobial, disinfectant or device used against any pest. Pests include insects, plant pathogens, weeds, mollusks, birds, mammals, fish, nematodes (roundworms) and microbes that compete with humans for food, destroy property, spread or are a vector for disease or are a nuisance. Many pesticides are poisonous to humans.
# Types of Pesticides
There are multiple ways of classifying pesticides.
- Bactericides for the control of bacteria
- Fungicides for the control of fungi and oomycetes
- Herbicides for the control of weeds
- Insecticides for the control of insects - these can be Ovicides (substances that kill eggs), Larvicides (substances that kill larvae) or Adulticides (substances that kill adult insects)
- Miticides for the control of mites
- Molluscicides for the control of slugs and snails
- Nematicides for the control of nematodes
- Rodenticides for the control of rodents
- Virucides for the control of viruses (e.g. H5N1)
Pesticides can also be classed as synthetic pesticides or biological pesticides, although the distinction can sometimes blur.
Broad-spectrum pesticides are those that kill an array of species, while narrow-spectrum, or selective pesticides only kill a small group of species.[2]
A systemic pesticide moves inside a plant following absorption by the plant. This movement is usually upward (through the xylem) and outward. Increased efficiency may be a result. Systemic insecticides which poison pollen and nectar in the flowers may kill needed pollinators such as bees.
Most pesticides work by poisoning pests.[3]
# Uses and benefits
Pesticides are used to control organisms which are considered harmful.[4] For example, they are used to kill mosquitoes that can transmit potentially deadly diseases like west nile virus and malaria. They can also kill bees, wasps or ants that can cause allergic reactions. Insecticides can protect animals, because infestations by parasites such as fleas may cause them illness.[4] Pesticides can prevent sickness in humans that could be caused by moldy food or diseased produce. Herbicides can prevent accidents by clearing roadside trees and brush, which may block visibility. They can also kill invasive weeds in parks and wilderness areas which may cause environmental damage. Herbicides are commonly applied in ponds and lakes to control algae and plants such as water grasses that can interfere with activities like swimming and fishing and cause the water to look or smell unpleasant.[5] Uncontrolled pests such as termites and mold can damage structures such as houses.[4] Pesticides are used in grocery stores and food storage facilities to manage rodents and insects that infest food such as grain. Each use of a pesticide carries some associated risk. Proper pesticide use decreases these associated risks to a level deemed acceptable and increases quality of life and protects property and the environment.
Pesticides save farmers money by preventing crop losses to insects and other pests; in the US, farmers get an estimated four-fold return on money they spend on pesticides.[6]
In 2006, the World Health Organization suggested the resumption of the limited use of DDT to fight malaria.[7] They called for the use of DDT to coat the inside walls of houses in areas where mosquitoes are prevalent. Dr. Arata Kochi, WHO's malaria chief, said, "One of the best tools we have against malaria is indoor residual house spraying. Of the dozen insecticides WHO has approved as safe for house spraying, the most effective is DDT."[7] Scientists estimate that DDT and other chemicals in the organophosphate class of pesticides have saved 7 million human lives since 1945 by preventing the transmission of diseases such as malaria, bubonic plague, sleeping sickness, and typhus.[2]
In the US, about a quarter of pesticides used are used in houses, yards, parks, golf courses, and swimming pools.[2] About 70% of the pesticides sold in the US are used in agriculture.[6]
# History
Since before 2500 BC, humans have used pesticides to prevent damage to their crops. The first known pesticide was elemental sulfur dusting used in Sumeria about 4,500 years ago. By the 15th century, toxic chemicals such as arsenic, mercury and lead were being applied to crops to kill pests. In the 17th century, nicotine sulfate was extracted from tobacco leaves for use as an insecticide. The 19th century saw the introduction of two more natural pesticides, pyrethrum which is derived from chrysanthemums, and rotenone which is derived from the roots of tropical vegetables.[8]
In 1939, Paul Müller discovered that DDT was a very effective insecticide. It quickly became the most widely-used pesticide in the world. However, in the 1960s, it was discovered that DDT was preventing many fish-eating birds from reproducing which was a huge threat to biodiversity. Rachel Carson wrote the best-selling book Silent Spring about biological magnification. DDT is now banned in at least 86 countries, but it is still used in some developing nations to prevent malaria and other tropical diseases by killing mosquitoes and other disease-carrying insects.[9]
In the 1940s manufacturers began to produce large amounts of synthetic pesticides and their use became widespread.[10] Some sources consider the 1940s and 1950s to have been the start of the "pesticide era."[11] Pesticide use has increased 50-fold since 1950 and 2.5 million tons (2.3 million metric tons) of industrial pesticides are now used each year.[8] Seventy-five percent of all pesticides in the world are used in developed countries, but use in developing countries is increasing.[2]
# Regulation
In most countries, in order to sell or use a pesticide, it must be approved by a government agency. For example, in the United States, the Environmental Protection Agency (EPA) does so. Complex and costly studies must be conducted to indicate whether the material is safe to use and effective against the intended pest. During the registration process, a label is created which contains directions for the proper use of the material. Based on acute toxicity, pesticides are assigned to a Toxicity Class. Intentional pesticide misuse is illegal worldwide.
Some pesticides are considered too hazardous for sale to the general public and are designated restricted use pesticides. Only certified applicators, who have passed an exam, may purchase or supervise the application of restricted use pesticides. Records of sales and use are required to be maintained and may be audited by government agencies charged with the enforcement of pesticide regulations.
"Read and follow label directions" is a phrase often quoted by extension agents, garden columnists and others teaching about pesticides. This is required by law in countries such as the US. Similar laws exist in limited parts of the rest of the world. In the US, the Federal Insecticide, Fungicide, and Rodenticide Act of 1972 (FIFRA) set up the current system of pesticide regulations. It was amended somewhat by the Food Quality Protection Act of 1996. Its purpose is to make pesticide manufacture, distribution and use as safe as possible. The most important points for users to understand are these: it is a violation to apply any pesticide in a manner not in accordance with the label for that pesticide, and it is a crime to do so intentionally.
# Environmental effects
Use of pesticides can have unintended effects on the environment. Over 98% of sprayed insecticides and 95% of herbicides reach a destination other than their target species, including nontarget species, air, water, bottom sediments, and food.[2] Pesticide contaminates land and water when it escapes from production sites and storage tanks, when it runs off from fields, when it is discarded, when it is sprayed aerially, and when it is sprayed into water to kill algae.[12] The amount of pesticide that migrates from the intended application area is influenced by the particular chemical's properties: its propensity for binding to soil, its vapor pressure, its water solubility, and its resistance to being broken down over time.[6] Factors in the soil, such as its texture, its ability to retain water, and the amount of organic matter contained in it, also affect the amount of pesticide that will leave the area.[6]
## Air
Pesticides can contribute to air pollution. Pesticide drift occurs when pesticides suspended in the air as particles are carried by wind to other areas, potentially contaminating them.[13] Pesticides that are applied to crops can volatilize and may be blown by winds into nearby areas, potentially posing a threat to wildlife.[14] Also, droplets of sprayed pesticides or particles from pesticides applied as dusts may travel on the wind to other areas,[15] or pesticides may adhere to particles that blow in the wind, such as dust particles.[16] Ground spraying produces less pesticide drift than aerial spraying does.[17] Farmers can employ a buffer zone around their crop, consisting of empty land or non-crop plants such as evergreen trees to serve as windbreaks and absorb the pesticides, preventing drift into other areas.[18] Such windbreaks are legally required in the Netherlands.[18]
Pesticides that are sprayed onto fields and used to fumigate soil can give off chemicals called volatile organic compounds, which can react with other chemicals and form a pollutant called ozone, accounting for an estimated 6% of the total ozone production.[19]
## Water
In the United States, pesticides were found to pollute every stream and over 90% of wells sampled in a study by the US Geological Survey.[20] Pesticide residues have also been found in rain and groundwater.[6] Studies by the UK government showed that pesticide concentrations exceeded those allowable for drinking water in some samples of river water and groundwater.[21]
Pesticide impacts on aquatic systems are often studied using a hydrology transport model to study movement and fate of chemicals in rivers and streams. As early as the 1970s quantitative analysis of pesticide runoff was conducted in order to predict amounts of pesticide that would reach surface waters.[22]
There are four major routes through which pesticides reach the water: it may drift outside of the intended area when it is sprayed, it may percolate, or leach, through the soil, it may be carried to the water as runoff, or it may be spilled, for example accidentally or through neglect.[23] They may also be carried to water by eroding soil.[24] Factors that affect a pesticide's ability to contaminate water include its water solubility, the distance from an application site to a body of water, weather, soil type, presence of a growing crop, and the method used to apply the chemical.[25]
In the US, the Environmental Protection Agency sets Maximum Contamination Levels, or maximum allowable concentrations for individual pesticides in public bodies of water.[6][25]
Similarly, the government of the United Kingdom sets Environmental Quality Standards (EQS), or maximum allowable concentrations of some pesticides in bodies of water above which toxicity may occur.[26] The European Union also regulates maximum concentrations of pesticides in water.[26]
## Soil
Many of the chemicals used in pesticides are persistent soil contaminants, whose impact may endure for decades and adversely affect soil conservation.[27]
The use of pesticides decreases the general biodiversity in the soil. Not using the chemicals results in higher soil quality,[28] with the additional effect that more organic matter in the soil allows for higher water retention.[6] This helps increase yields for farms in drought years, when organic farms have had yields 20-40% higher than their conventional counterparts.[29] A smaller content of organic matter in the soil increases the amount of pesticide that will leave the area of application, because organic matter binds to and helps break down pesticides.[6]
## Plants
Nitrogen fixation, which is required for the growth of higher plants, is hindered by pesticides in soil.[30] The insecticides DDT, methyl parathion, and especially pentachlorophenol have been shown to interfere with legume-rhizobium chemical signaling.[30] Reduction of this symbiotic chemical signaling results in reduced nitrogen fixation and thus reduced crop yields.[30] Root nodule formation in these plants saves the world economy $10 billion in synthetic nitrogen fertiliser every year.[31]
Pesticides can kill bees and are strongly implicated in pollinator decline, the loss of species that polinate plants, including through the mechanism of Colony Collapse Disorder,[32][33][34][35] in which worker bees from a beehive or Western honey bee colony abruptly disappear. Application of pesticides to crops that are in bloom can kill honeybees,[13] which act as pollinators. The USDA and USFWS estimate that US farmers lose at least $200 million a year from reduced crop pollination because pesticides applied to fields eliminate about a fifth of honeybee colonies in the US and harm an additional 15%.[2]
## Persistent organic pollutants
Persistent organic pollutants (POPs) are compounds that resist degradation and thus remain in the environment for years.[36] Some pesticides, including aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and toxaphene, are considered POPs.[36] POPs have the ability to volatilize and travel great distances through the atmosphere to become deposited in remote regions.[36] The chemicals also have the ability to bioaccumulate and biomagnify, and can bioconcentrate (i.e. become more concentrated) up to 70,000 times their original concentrations.[36] POPs may continue to poison non-target organisms in the environment and increase risk to humans[37] by disruption in the endocrine, reproductive, and immune systems; cancer; neurobehavioral disorders,[36] infertility and mutagenic effects, although very little is currently known about these chronic effects. Some POPs have been banned, while others continue to be used.
## Animals
Pesticides inflict extremely widespread damage to biota, and many countries have acted to discourage pesticide usage through their Biodiversity Action Plans.[citation needed]
Animals may be poisoned by pesticide residues that remain on food after spraying, for example when wild animals enter sprayed fields or nearby areas shortly after spraying.[17]
Widespread application of pesticides can eliminate food sources that certain types of animals need, causing the animals to relocate, change their diet, or starve.[13] Poisoning from pesticides can travel up the food chain; for example, birds can be harmed when they eat insects and worms that have consumed pesticides.[13] Some pesticides can bioaccumulate, or build up to toxic levels in the bodies of organisms that consume them over time, a phenomenon that impacts species high on the food chain especially hard.[13]
The USDA and USFWS estimate that about 20% of the endangered and threatened species in the US are jeopardized by use of pesticides.[2]
### Birds
Birds are common examples of nontarget organisms that are impacted by pesticide use. Rachel Carson's landmark book Silent Spring dealt with the topic of loss of bird species due to bioaccumulation of pesticides in their tissues. There is evidence that birds are continuing to be harmed by pesticide use. In the farmland of Britain, populations of ten different species of birds have declined by 10 million breeding individuals between 1979 and 1999, a phenomenon thought to have resulted from loss of plant and invertebrate species on which the birds feed.[38] Throughout Europe, 116 species of birds are now threatened.[38] Reductions in bird populations have been found to be associated with times and areas in which pesticides are used.[38] In another example, some types of fungicides used in peanut farming are only slightly toxic to birds and mammals, but may kill off earthworms, which can in turn reduce populations of the birds and mammals that feed on them.[17]
Some pesticides come in granular form, and birds an other wildlife may eat the granules, mistaking them for grains of food.[17] A few granules of a pesticide is enough to kill a small bird.[17]
The herbicide paraquat, when sprayed onto bird eggs, causes growth abnormalities in embryos and reduces the number of chicks that hatch successfully, but most herbicides do not directly cause much harm to birds.[17] Herbicides may endanger bird populations by reducing their habitat.[17]
The USDA and USFWS estimate that over 67 million birds are killed by pesticides each year in the US.[2]
### Aquatic life
Fish and other aquatic biota may be harmed by pesticide-contaminated water.[5] Pesticide surface runoff into rivers and streams can be highly lethal to aquatic life, sometimes killing all the fish in a particular stream.[39] For example, in Montague P.E.I., nine "fish kills" happened in one year: every fish, snake, and snail was killed in a river called Sutherland's Hole near potato farms from which herbicides, insecticides, and fungicides ran off after heavy rains.[39] Pesticide-related fish kills are frequently unreported and likely underestimated.[5]
Application of herbicides to bodies of water can cause fish kills when the dead plants rot and use up the water's oxygen, suffocating the fish.[5] Some herbicides, such as copper sulfite, that are applied to water to kill plants are toxic to fish and other water animals at concentrations similar to those used to kill the plants.[5]
Pesticides can accumulate in bodies of water to levels that kill off zooplankton, the main source of food for young fish.[40]
The USDA and USFWS estimate that between 6 and 14 million fish are killed by pesticides each year in the US.[2]
The faster a given pesticide breaks down in the environment, the less threat it poses to aquatic life.[5] Insecticides are more toxic to aquatic life than herbicides and fungicides.[5]
### Amphibians
Some scientists believe that certain common pesticides already exist at levels capable of killing amphibians in California.[41] They warn that the breakdown products of these pesticides can be 10 to 100 times more toxic to amphibians than the original pesticides.[41] Direct contact of sprays of some pesticides (either by drift from nearby applications or accidental or deliberate sprays) can be highly lethal to amphibians.[42]
US scientists have found that some pesticides used in farming disrupt the nervous systems of frogs, and that use of these pesticides is correlated with a decline in the population of frogs in the Sierra Nevada.[43] In the past several decades, decline in amphibian populations has been occurring all over the world, for unexplained reasons which are thought to be varied but of which pesticides may be a part.[43] Being downwind from agricultural land on which pesticides are used has been linked to the decline in population of threatened frog species in California.[44]
In Minnesota, pesticide use has been causally linked to congenital deformities in frogs such as eye, mouth, and limb malformations.[45] Researchers in California found that similar deformities in frogs in the US and Canada may have been caused by breakdown products from pesticides which themselves did not pose a threat.[46]
## Pest resistance
An early discovery relating to pesticide use is that pests may eventually evolve to become resistant to chemicals. When sprayed with pesticides, many pests will initially be very susceptible. However, not all pests are killed, and some with slight variations in their genetic makeup are resistant and therefore survive. Through natural selection, the pests may eventually become very resistant to the pesticide.
Pest resistance to a pesticide is commonly managed through pesticide rotation, which involves alternating among pesticide classes with different modes of action to delay the onset of or mitigate existing pest resistance.[11]
Tankmixing pesticides is the combination of two or more pesticides with different modes of action in order to improve individual pesticide application results and delay the onset of or mitigate existing pest resistance.[citation needed]
## Pest rebound and secondary pest outbreaks
Non-target organisms, organisms that the pesticides are not intended to kill, can be severely impacted by use of the chemicals. In some cases, where a pest insect has some controls from a beneficial predator or parasite, an insecticide application can kill both pest and beneficial populations. A study comparing biological pest control and use of pyrethroid insecticide for diamondback moths, a major cabbage family insect pest, showed that the insecticide application created a rebounded pest population due to loss of insect predators, whereas the biocontrol did not show the same effect.[47] Likewise, pesticides sprayed in an effort to control adult mosquitoes, may temporarily depress mosquito populations, however they may result in a larger population in the long run by damaging the natural controlling factors.[13] This phenomenon, wherein the population of a pest species rebounds to equal or greater numbers than it had before pesticide use, is called pest resurgence and can be linked to elimination of predators and other natural enemies of the pest.[10]
Loss of predator species can also lead to a related phenomenon called secondary pest outbreaks, an increase in problems from species which were not originally very damaging pests due to loss of their predators or parasites.[10] An estimated third of the 300 most damaging insects in the US were originally secondary pests and only became a major problem after the use of pesticides.[2] In both pest resurgence and secondary pest outbreaks, the natural enemies have been found to be more susceptible to the pesticides than the pests themselves, in some cases causing the pest population to be higher than it was before the use of pesticide.[10]
# Health effects
Pesticides can present danger to consumers, bystanders, or workers during manufacture, transport, or during and after use.[48]
## Farmers
There have been many studies of farmers with the goal of determining the health effects of pesticide exposure.[49]
The World Health Organization and the UN Environment Programme estimate that each year, 3 million workers in agriculture in the developing world experience severe poisoning from pesticides, about 18,000 of whom die.[2]
Research in Bangladesh suggests that many farmers do not need to apply pesticide to their rice fields, but continue to do so only because the pesticide is paid for by the government.[50] Organophosphate pesticides have increased in use, because they are less damaging to the environment and they are less persistent than organochlorine pesticides.[51] These are associated with acute health problems such as abdominal pain, dizziness, headaches, nausea, vomiting, as well as skin and eye problems.[52] Additionally, many studies have indicated that pesticide exposure is associated with long-term health problems such as respiratory problems, memory disorders, dermatologic conditions,[53][54] cancer,[55] depression, neurologic deficits,[56][57] miscarriages, and birth defects.[58][59][60][61][62][63][64][65][66] Summaries of peer-reviewed research have examined the link between pesticide exposure and neurologic outcomes and cancer, perhaps the two most significant things resulting in organophosphate-exposed workers.[67][68]
## Consumers
There is concern that pesticides used to control pests on food crops are dangerous to people who consume those foods. These concerns are one reason for the organic food movement. Many food crops, including fruits and vegetables, contain pesticide residues after being washed or peeled (see Pesticide residues in food, below). In the US, levels of residues that remain on foods are limited to tolerance levels that are established by the US EPA and are considered safe.[69] The EPA sets the tolerances based on the toxicity of the pesticide and its break-down products, the amount and frequency of pesticide application, and how much of the pesticide (i.e., the residue) remains in or on food by the time it is marketed and prepared.[70] Tolerance levels are obtained using scientific risk assessments that pesticide manufacturers are required to produce by conducting toxicological studies, exposure modeling and residue studies before a particular pesticide can be registered, however, the effects are tested for single pesticides, and there is no information on possible synergistic effects of exposure to multiple pesticide traces in the air, food and water.[71]
In the US, the National Academy of Sciences estimates that between 4,000 and 20,000 cases of cancer are caused per year by pesticide residues in food in allowable amounts.[2]
A new study conducted by the Harvard School of Public Health in Boston, has discovered a 70% increase in the risk of developing Parkinson’s disease for people exposed to even low levels of pesticides.[72]
A study published by the United States National Research Council in 1993 determined that for infants and children, the major source of exposure to pesticides is through diet.[73] A study in 2006 measured the levels of organophosphorus pesticide exposure in 23 school children before and after replacing their diet with organic food (food grown without synthetic pesticides). In this study it was found that levels of organophosphorus pesticide exposure dropped dramatically and immediately when the children switched to an organic diet.[74]
### Pesticide residues in food
The Pesticide Data Program, a program started by the United States Department of Agriculture is the largest tester of pesticide residues on food sold in the United States. It began in 1990, and has since tested over 60 different types of food for over 400 different types of pesticides - with samples collected close to the point of consumption. Their most recent summary results are from the year 2005:[75]
For example, on page 30 is comprehensive data on pesticides on fruits. Some example data:
They were also able to test for multiple pesticides within a single sample and found that:
The Environmental Working Group used the results of nearly 43,000 tests for pesticides on produce collected by the USDA and the U.S. FDA between 2000 and 2004, to produce a ranking of 43 commonly eaten fruits & vegetables.[76]
## The public
Exposure routes other than consuming food that contains residues, in particular pesticide drift, are potentially significant to the general public.[77]
The Bhopal disaster occurred when a pesticide plant released 40 tons of methyl isocyanate (MIC) gas, intermediate chemical in the production of some pesticides. The disaster immediately killed nearly 3,000 people and ultimately caused at least 15,000 deaths.[78]
Children have been found to be especially susceptible to the harmful effects of pesticides.[79] A number of research studies have found higher instances of brain cancer, leukemia and birth defects in children with early exposure to pesticides, according to the Natural Resources Defense Council.[80]
Peer-reviewed studies now suggest neurotoxic effects on developing animals from organophosphate pesticides at legally-tolerable levels, including fewer nerve cells, lower birth weights, and lower cognitive scores.[citation needed] The EPA finished a 10 year review of the organophosphate pesticides following the 1996 Food Quality Protection Act, but did little to account for developmental neurotoxic effects, drawing strong criticism from within the agency and from outside researchers.[81][82]
Some scientists think that exposure to pesticides in the uterus may have negative effects on a fetus that may manifest as problems such as growth and behavioral disorders or reduced resistance to pesticide toxicity later in life.[83]
One study found that use of pesticides may be behind the finding that the rate of birth defects such as missing or very small eyes is twice as high in rural areas as in urban areas.[84] Another study found no connection between eye abnormalities and pesticides.[84]
Pyrethrins, insecticides commonly used in common bug killers, can cause a potentially deadly condition if breathed in.[85]
# Continuing development of pesticides
Pesticide safety education and pesticide applicator regulation are designed to protect the public from pesticide misuse, but do not eliminate all misuse. Reducing the use of pesticides and replacing high risk pesticides is a solution to reducing risks placed on our society from pesticide use.[citation needed] For over 30 years, there has been a trend in the United States and in many other parts of the world to use pesticides in combination with alternative pest controls.[citation needed] Integrated pest management, the use of multiple approaches to control pests, is becoming widespread and has been used with success in countries such as Indonesia, China, Bangladesh, the US, Australia, and Mexico.[2] IPM attempts to recognize the more widespread impacts of an action on an ecosystem, so that natural balances are not upset.[10] With pesticide regulations that now put a higher priority on reducing the risks of pesticides in the food supply and emphasize environmental protection, old pesticides are being phased out in favor of new reduced risk pesticides.[citation needed] These new pesticides include biological and botanical derivatives and alternatives that are thought to reduce health and environmental risks. Chemical engineers continually develop new pesticides to produce enhancements over previous generations of products.[citation needed] In addition, applicators are being encouraged to consider alternative controls and adopt methods that reduce the use of chemical pesticides. This process is ongoing and is not an immediate solution to the risks of pesticide use.[citation needed]
Pesticides can be created that are targeted to a specific pest's life cycle, which can be more environmentally-friendly.[86] For example, potato cyst nematodes emerge from their protective cysts in response to a chemical excreted by potatoes; they feed on the potatoes and damage the crop.[86] A similar chemical can be applied to fields early, before the potatoes are planted, causing the nematodes to emerge early and starve in the absence of potatoes.[86]
# Alternatives
Alternatives to pesticides are available and include methods of cultivation, use of other organisms to kill pests, genetic engineering, and interfering with insect breeding.[2]
Cultivation practices include polyculture (growing multiple types of plants), crop rotation, planting crops in areas where the pests that damage them do not live, timing planting according to when pests will be least problematic, use of trap crops that attract pests away from the real crop.[2] In the US, farmers have had success controlling insects by spraying with hot water at a cost that is about the same as pesticide spraying.[2]
Release of other organisms that fight the pest is another example of an alternative to pesticide use. These organisms can include natural predators or parasites of the pests.[2] Pathogens such as bacteria and viruses which cause disease in the pest species can also be used.[2]
Interfering with insects' reproduction can be accomplished by sterilizing males of the target species and releasing them, so that they mate with females but do not produce offspring.[2] This technique was first used on the screwworm fly in 1958 and has since been used with the medfly, the tsetse fly,[87] and the gypsy moth.[88] However, this can be a costly, time consuming approach that only works on some types of insects.[2]
Some evidence shows that alternatives to pesticides can be equally effective as the use of chemicals. For example, Sweden has halved its use of pesticides with hardly any reduction in crops.[2] In Indonesia, farmers have reduced pesticide use on rice fields by 65% and experienced a 15% crop increase.[2] | https://www.wikidoc.org/index.php/Pesticide | |
4128d0131a38961184279f1e49d984acf6784641 | wikidoc | Phagocyte | Phagocyte
A phagocyte is a cell that ingests and destroys foreign matter such as microorganisms or debris by a process known as phagocytosis.
# Types of Phagocytes
There are two main categories of phagocytes:
- macrophages (and monocytes)
- microphages, such as polymorphonuclear leukocytes (primarily neutrophils)
# Functions of Phagocytes
Phagocytes are extremely useful as an initial immune system response to infection. If the skin is broken, neutrophils are the first type of phagocyte to migrate to sites of injury and fight bacteria by releasing cytotoxic granules and by phagocytosis. Phagocytosis is an active process in wound healing.
Phagocytes contain many lysosomes that enable them to digest foreign material. Phagocytes engulf pathogens, debris, dead or dying cells and extracellular matrix. After engulfment into a phagosome, a lysosome which is filled with digestive enzymes (proteases and oxygen radicals) will fuse with it to form the phagolysosome. The two compartments become one phagolysosome, in which the phagocytosed material is digested.
In the case of pathogen phagocytosis, professional antigen-presenting cells (i.e.: dendritic cells and macrophages) will present on their surfaces small peptides that resulted from the digestion, bound to MHC class II molecules. Helper T cells (CD4+) later recognize these antigens presented through MHC class II complemented with a second signal and they will further supplement the cell mediated immune response.
In addition to engulfing and digesting foreign particles, phagocytes can induce apoptosis of normal and tumor cells, produce cationic proteins, complement components and clotting factors, arachidonic acid metabolites, prostaglandins, leukotrienes, thromboxanes, cytokines, proteases and hydrolases, reactive oxygen and nitrogen intermediates.
# Pathogen Resistance to phagocytes
Many pathogens can delay or prevent the creation of the phagolysosome such as Mycobacterium tuberculosis, Salmonella typhi and Legionella. Others, such as the parasites of the genus Leishmania, are capable of resisting or circumventing being digested in the phagolysosome.
One function of T-helper cells is to activate phagocytes to digest intracellular pathogens.
# Etymology
The word phagocyte etymologically means "cell that eats", originating from the Greek words phagein, meaning 'eat', and kytos, meaning 'hollow'. | Phagocyte
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A phagocyte is a cell that ingests and destroys foreign matter such as microorganisms or debris by a process known as phagocytosis.
# Types of Phagocytes
There are two main categories of phagocytes: [1]
- macrophages (and monocytes)
- microphages, such as polymorphonuclear leukocytes (primarily neutrophils)
# Functions of Phagocytes
Phagocytes are extremely useful as an initial immune system response to infection. If the skin is broken, neutrophils are the first type of phagocyte to migrate to sites of injury and fight bacteria by releasing cytotoxic granules and by phagocytosis. Phagocytosis is an active process in wound healing.
Phagocytes contain many lysosomes that enable them to digest foreign material. Phagocytes engulf pathogens, debris, dead or dying cells and extracellular matrix. After engulfment into a phagosome, a lysosome which is filled with digestive enzymes (proteases and oxygen radicals) will fuse with it to form the phagolysosome. The two compartments become one phagolysosome, in which the phagocytosed material is digested.
In the case of pathogen phagocytosis, professional antigen-presenting cells (i.e.: dendritic cells and macrophages) will present on their surfaces small peptides that resulted from the digestion, bound to MHC class II molecules. Helper T cells (CD4+) later recognize these antigens presented through MHC class II complemented with a second signal and they will further supplement the cell mediated immune response.
In addition to engulfing and digesting foreign particles, phagocytes can induce apoptosis of normal and tumor cells, produce cationic proteins, complement components and clotting factors, arachidonic acid metabolites, prostaglandins, leukotrienes, thromboxanes, cytokines, proteases and hydrolases, reactive oxygen and nitrogen intermediates.
# Pathogen Resistance to phagocytes
Many pathogens can delay or prevent the creation of the phagolysosome such as Mycobacterium tuberculosis, Salmonella typhi and Legionella. Others, such as the parasites of the genus Leishmania, are capable of resisting or circumventing being digested in the phagolysosome.
One function of T-helper cells is to activate phagocytes to digest intracellular pathogens.
# Etymology
The word phagocyte etymologically means "cell that eats", originating from the Greek words phagein, meaning 'eat', and kytos, meaning 'hollow'. | https://www.wikidoc.org/index.php/Phagocyte | |
609c8854c385d70dc1e1c56193286a1408d31d4a | wikidoc | Pheromone | Pheromone
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A pheromone is a chemical that triggers a natural behavioral response in another member of the same species. There are alarm pheromones, food trail pheromones, sex pheromones, and many others that affect behavior or physiology. Their use among insects has been particularly well documented, although many vertebrates and plants also communicate using pheromones.
# Explanation
Pheromones of the Raydon Cheadle Navarro insect species, such as the Japanese beetle and the gypsy moth, can be used to induce many behaviors. This facilitates trapping for monitoring purposes and population control by creating confusion, disrupting mating and preventing them from laying eggs.
In mammals and reptiles, pheromones may be detected by the vomeronasal organ, or Jacobson's organ, which lies between the nose and mouth and is the first stage of the accessory olfactory system. Some pheromones in these animals are detected by regular olfactory membranes.
The term "pheromone" was introduced by Peter Karlson and Martin Lüscher in 1959, based on the Greek pherein (to transport) and hormon (to stimulate). They proposed the term to describe chemical signals from conspecifics which elicit innate behaviours soon after Butenandt characterized the first such chemical, Bombykol (a chemically well-characterized pheromone released by the female silkworm to attract mates).
# Types of pheromones
## Aggregation pheromones
Produced by one or the other sex, these pheromones attract individuals of both sexes.
## Alarm pheromones
Some species release a volatile substance when attacked by a predator that can trigger flight (in aphids) or aggression (in bees) in members of the same species. Pheromones also exist in plants:certain plants emit alarm pheromones when grazed upon, resulting in tannin production in neighboring plants. These tannins make the plants less appetizing for the herbivore.
## Epideictic pheromones
Recognized in insects, these pheromones are different from territory pheromones. According to Fabre (translated from French), "Females who lay their eggs in these fruits deposit these mysterious substances in the vicinity of their clutch to signal to other females of the same species so that they will clutch elsewhere."
## Releaser pheromones
Powerful attractant molecules that some organisms may use to attract mates from a distance of 2 miles or more. This type of pheromone generally elicites rapid response but is quickly degraded. In contrast, a primer pheromone would have a slower onset but a longer duration.
## Primer pheromones
These pheromones trigger a change of developmental events.
## Territorial pheromones
Laid down in the environment, these pheromones mark the boundaries of an organism's territory. In dogs, these hormones are present in the urine, which they deposit on landmarks serving to mark the perimeter of the claimed territory.
## Trail pheromones
These pheromones are common in social insects. For example, ants mark their paths with these pheromones, which are non-volatile hydrocarbons.
Certain ants lay down an initial trail of pheromones as they return to the nest with food. This trail attracts other ants and serves as a guide. As long as the food source remains, the pheromone trail will be continually renewed. The pheromone must be continually renewed because it evaporates quickly. When the supply begins to dwindle, the trailmaking ceases. In at least one species of ant, trails that no longer lead to food are also marked with a repellent pheromone.
## Sex pheromones
In animals, sex pheromones indicate the availability of the female for breeding. Many insect species release sex pheromones to attract a mate and many lepidopterans can detect a potential mate from as far away as 10 km (6.2 miles). Pheromones can be used in gametes to trail the opposite sex's gametes for fertilization. Pheromones are also used in the detection of oestrus in sows. Boar pheromones are sprayed into the sty, and those sows which exhibit sexual arousal are known to be currently available for breeding.
Male animals also emit pheromones that convey information about what species they are, and their genotype. The purpose of pheromones giving information about genotype is a mechanism to avoid inbreeding. Females are attracted to males with the least similar genotype, which means they are attracted to males who are the least likely to be related to them. An exception to this is when the female is pregnant. Then they are most drawn to individuals with the most similar pheromones (and therefore genotype) most likely because they want to keep family close by to aid with the raising of their young and to take advantage of protection.
## Other pheromones (not yet classified)
This classification, based on the effects on behavior, remains artificial. Pheromones fill many additional functions.
- Nasonov pheromones (worker bees)
- Royal pheromones (bees)
- Calming (appeasement) pheromones (mammals)
# Human pheromones
A few well-controlled scientific studies have been published suggesting the possibility of pheromones in humans. The best-studied case involves the synchronization of menstrual cycles among women based on unconscious odor cues (the so called McClintock effect, named after the primary investigator). This study proposes that there are two types of pheromone involved: "One, produced prior to ovulation, shortens the ovarian cycle; and the second, produced just at ovulation, lengthens the cycle". This is analogous to the Whitten effect, a male pheromone mediated modulation of estrus observed in mice.
Other studies have suggested that people might be using odor cues associated with the immune system to select mates who are not closely related to themselves. (See Disassortative sexual selection) Using a brain imaging technique, Swedish researchers have shown that homosexual and heterosexual males' brains respond differently to two odors that may be involved in sexual arousal, and that the homosexual men respond in the same way as heterosexual women. The study was expanded to include lesbian women and the results were consistent with previous findings meaning that homosexual women were not as responsive to male identified odors but their response to female cues was similar to heterosexual males. According to the researchers, this research suggests a possible role for human pheromones in the biological basis of sexual orientation.
Another study demonstrated that the smell of androstadienone, a chemical component of male sweat, maintains higher levels of cortisol in females. The scientists suggest that the ability of this compound to influence the endocrine balance of the opposite sex makes it a human pheromonal chemosignal.
In 2006 it was shown that a second mouse receptor sub-class is found in the olfactory epithelium. Called the trace amine-associated receptors (TAAR), some are activated by volatile amines found in mouse urine, including one putative mouse pheromone. Orthologous receptors exist in humans providing, the authors propose, evidence for a mechanism of human pheromone detection.
Some commercially-available substances are advertised using claims that the products contain human sexual pheromones and can act as an aphrodisiac. These often lack credibility due to an excessive marketing of pheromones by unsolicited e-mail. Despite claims to the contrary, no defined pheromonal substance has ever been demonstrated to directly influence human behavior in a peer reviewed, published study. | Pheromone
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 [6] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A pheromone is a chemical that triggers a natural behavioral response in another member of the same species. There are alarm pheromones, food trail pheromones, sex pheromones, and many others that affect behavior or physiology. Their use among insects has been particularly well documented, although many vertebrates and plants also communicate using pheromones.
# Explanation
Pheromones of the Raydon Cheadle Navarro insect species, such as the Japanese beetle and the gypsy moth, can be used to induce many behaviors. This facilitates trapping for monitoring purposes and population control by creating confusion, disrupting mating and preventing them from laying eggs.
In mammals and reptiles, pheromones may be detected by the vomeronasal organ, or Jacobson's organ, which lies between the nose and mouth and is the first stage of the accessory olfactory system. Some pheromones in these animals are detected by regular olfactory membranes.
The term "pheromone" was introduced by Peter Karlson and Martin Lüscher in 1959, based on the Greek pherein (to transport) and hormon (to stimulate). They proposed the term to describe chemical signals from conspecifics which elicit innate behaviours soon after Butenandt characterized the first such chemical, Bombykol (a chemically well-characterized pheromone released by the female silkworm to attract mates).[1]
# Types of pheromones
## Aggregation pheromones
Produced by one or the other sex, these pheromones attract individuals of both sexes.
## Alarm pheromones
Some species release a volatile substance when attacked by a predator that can trigger flight (in aphids) or aggression (in bees) in members of the same species. Pheromones also exist in plants:certain plants emit alarm pheromones when grazed upon, resulting in tannin production in neighboring plants. These tannins make the plants less appetizing for the herbivore.
## Epideictic pheromones
Recognized in insects, these pheromones are different from territory pheromones. According to Fabre (translated from French), "Females who lay their eggs in these fruits deposit these mysterious substances in the vicinity of their clutch to signal to other females of the same species so that they will clutch elsewhere."
## Releaser pheromones
Powerful attractant molecules that some organisms may use to attract mates from a distance of 2 miles or more. This type of pheromone generally elicites rapid response but is quickly degraded. In contrast, a primer pheromone would have a slower onset but a longer duration.
## Primer pheromones
These pheromones trigger a change of developmental events.
## Territorial pheromones
Laid down in the environment, these pheromones mark the boundaries of an organism's territory. In dogs, these hormones are present in the urine, which they deposit on landmarks serving to mark the perimeter of the claimed territory.
## Trail pheromones
These pheromones are common in social insects. For example, ants mark their paths with these pheromones, which are non-volatile hydrocarbons.
Certain ants lay down an initial trail of pheromones as they return to the nest with food. This trail attracts other ants and serves as a guide.[2] As long as the food source remains, the pheromone trail will be continually renewed. The pheromone must be continually renewed because it evaporates quickly. When the supply begins to dwindle, the trailmaking ceases. In at least one species of ant, trails that no longer lead to food are also marked with a repellent pheromone.[3]
## Sex pheromones
In animals, sex pheromones indicate the availability of the female for breeding. Many insect species release sex pheromones to attract a mate and many lepidopterans can detect a potential mate from as far away as 10 km (6.2 miles). Pheromones can be used in gametes to trail the opposite sex's gametes for fertilization. Pheromones are also used in the detection of oestrus in sows. Boar pheromones are sprayed into the sty, and those sows which exhibit sexual arousal are known to be currently available for breeding.
Male animals also emit pheromones that convey information about what species they are, and their genotype. The purpose of pheromones giving information about genotype is a mechanism to avoid inbreeding. Females are attracted to males with the least similar genotype, which means they are attracted to males who are the least likely to be related to them. An exception to this is when the female is pregnant. Then they are most drawn to individuals with the most similar pheromones (and therefore genotype) most likely because they want to keep family close by to aid with the raising of their young and to take advantage of protection.
## Other pheromones (not yet classified)
This classification, based on the effects on behavior, remains artificial. Pheromones fill many additional functions.
- Nasonov pheromones (worker bees)
- Royal pheromones (bees)
- Calming (appeasement) pheromones (mammals)
# Human pheromones
A few well-controlled scientific studies have been published suggesting the possibility of pheromones in humans. The best-studied case involves the synchronization of menstrual cycles among women based on unconscious odor cues (the so called McClintock effect, named after the primary investigator). This study proposes that there are two types of pheromone involved: "One, produced prior to ovulation, shortens the ovarian cycle; and the second, produced just at ovulation, lengthens the cycle". This is analogous to the Whitten effect,[4][5] a male pheromone mediated modulation of estrus observed in mice.
Other studies have suggested that people might be using odor cues associated with the immune system to select mates who are not closely related to themselves. (See Disassortative sexual selection) Using a brain imaging technique, Swedish researchers have shown that homosexual and heterosexual males' brains respond differently to two odors that may be involved in sexual arousal, and that the homosexual men respond in the same way as heterosexual women. The study was expanded to include lesbian women and the results were consistent with previous findings meaning that homosexual women were not as responsive to male identified odors but their response to female cues was similar to heterosexual males.[6] According to the researchers, this research suggests a possible role for human pheromones in the biological basis of sexual orientation.[7]
Another study demonstrated that the smell of androstadienone, a chemical component of male sweat, maintains higher levels of cortisol in females. The scientists suggest that the ability of this compound to influence the endocrine balance of the opposite sex makes it a human pheromonal chemosignal.[8]
In 2006 it was shown that a second mouse receptor sub-class is found in the olfactory epithelium. Called the trace amine-associated receptors (TAAR), some are activated by volatile amines found in mouse urine, including one putative mouse pheromone.[9] Orthologous receptors exist in humans providing, the authors propose, evidence for a mechanism of human pheromone detection.[10]
Some commercially-available substances are advertised using claims that the products contain human sexual pheromones and can act as an aphrodisiac. These often lack credibility due to an excessive marketing of pheromones by unsolicited e-mail. Despite claims to the contrary, no defined pheromonal substance has ever been demonstrated to directly influence human behavior in a peer reviewed, published study.[11] | https://www.wikidoc.org/index.php/Pheromone | |
8d366a52e3f58273dd6eb835abd57f32be77a1fa | wikidoc | Phosducin | Phosducin
Phosducin, also known as PDC, is a human protein and gene. It belongs to the phosducin family of proteins.
This gene encodes a phosphoprotein, which is located in the outer and inner segments of the rod cells in the retina. This protein may participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism. It modulates the phototransduction cascade by interacting with the beta and gamma subunits of the retinal G-protein transducin. By associating with these subunits only, the Transducin alpha subunit will remain active for longer. This will increase the amount of time of visual excitation.
This gene is a potential candidate gene for retinitis pigmentosa and Usher syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. | Phosducin
Phosducin, also known as PDC, is a human protein and gene.[1] It belongs to the phosducin family of proteins.
This gene encodes a phosphoprotein, which is located in the outer and inner segments of the rod cells in the retina. This protein may participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism. It modulates the phototransduction cascade by interacting with the beta and gamma subunits of the retinal G-protein transducin. By associating with these subunits only, the Transducin alpha subunit will remain active for longer. This will increase the amount of time of visual excitation.
This gene is a potential candidate gene for retinitis pigmentosa and Usher syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified.[1] | https://www.wikidoc.org/index.php/Phosducin | |
811747d6133bf635fd4bb2af40f286e302a84b65 | wikidoc | Photopsia | Photopsia
# Overview
Photopsia is the presence of perceived flashes of light. It is most commonly associated with posterior vitreous detachment, migraine with aura, migraine aura without headache, retinal break or detachment, occipital lobe infarction, and sensory deprivation (ophthalmopathic hallucinations). Vitreous shrinkage or liquefaction, which are the most common causes of photopsia, cause a pull in vitreoretinal attachments, irritating the retina and causing it to discharge electrical impulses. These impulses are interpreted by the brain as 'flashes'.
This condition has also been identified as a common initial symptom of Punctate inner choroiditis (PIC), a rare retinal autoimmune disease believed to be caused by the immune system mistakenly attacking and destroying the retina. During pregnancy, new-onset photopsia is concerning for severe preeclampsia.
# Differential diagnosis of causes of photopsia
It is most commonly associated with posterior vitreous detachment, migraine with aura, migraine aura without headache and retinal break or retinal detachment.
## Drug Side Effect
- Crizotinib
- Verteporfin | Photopsia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Photopsia is the presence of perceived flashes of light. It is most commonly associated with posterior vitreous detachment, migraine with aura, migraine aura without headache, retinal break or detachment, occipital lobe infarction, and sensory deprivation (ophthalmopathic hallucinations). Vitreous shrinkage or liquefaction, which are the most common causes of photopsia, cause a pull in vitreoretinal attachments, irritating the retina and causing it to discharge electrical impulses. These impulses are interpreted by the brain as 'flashes'.
This condition has also been identified as a common initial symptom of Punctate inner choroiditis (PIC), a rare retinal autoimmune disease believed to be caused by the immune system mistakenly attacking and destroying the retina. During pregnancy, new-onset photopsia is concerning for severe preeclampsia.
# Differential diagnosis of causes of photopsia
It is most commonly associated with posterior vitreous detachment, migraine with aura, migraine aura without headache and retinal break or retinal detachment.
## Drug Side Effect
- Crizotinib
- Verteporfin | https://www.wikidoc.org/index.php/Photopsia | |
70911e3c5fc91dfe51c51bcd02443a00ecb9a262 | wikidoc | Picamilon | Picamilon
Picamilon is a compound formed by reacting niacin with GABA. It was invented in Russia. Picamilon is able to cross the blood-brain barrier and activate GABA receptors, producing an anxiolytic response. The niacin also acts as a strong vasodialator, helping to improve awareness.
Studies from Russia demonstrate that Picamilon improves nervous control, recovery time after work, blood pressure and memory. The drug even shows benefits in treating brain trauma.
An essential role in the mechanism of action of Picamilon is its effect on nervous control of the cerebral circulation. It weakens changes in cerebral blood flow during the vasomotor reflex, considerably inhibits constrictor responses of vessels in the carotid and vertebrobasilar basins due to stimulation of afferent fibers of somatic nerves, and causes gradually developing inhibition of tonic and reflex activity in sympathetic nerves.
Neuropharmacological screening tests on Picamilon have demonstrated its tranquilizing properties in small doses. For instance, at a dose of l mg/kg, Picamilon prevents the negative consequences of emotional stress (in cats it normalizes the orienting reaction when disturbed by the response to rage and fear). Like diazepam, it has an inhibitory effect on motivated aggression, associated with fighting for territory in rats.
Investigation of Picamilon's effect on the threshold of "self-stimulation" showed that in higher doses (80 and 160 mg/kg), in contrast with small doses which have a tranquilizing effect, Picamilon lowered the "self-stimulation" threshold (like amphetamine), but at the same time reduced the number of self-stimulation. The stimulating action of the drug also has been shown in general anesthesia. For instance, at a dose of 100 mg/kg, Picamilon reduced by 1.7 times the duration of the sedative effect of hexobarbital sodium and reduced by half the duration of thiopental anesthesia.
Unlike tranquilizer drugs (chlorodiazepoxide, diazepam, relanium, phenazepam), Picamilon does not induce muscle relaxation, drowsiness or lethargy. Clinicians have stated that the drug closely resembles cavinton (the ethyl ester of apovincamic acid), but comparison of the properties of the two compounds showed that Picamilon is superior.
Picamilon produces no allergenic, teratogenic, embryotoxic or carcinogenic effects. On this basis, the pharmacological committee of the Ministry of the Health (Russia) recommended clinical trials of Picamilon for cerebrovascular disturbances, as a daytime tranquilizer, as a stimulant in depressive and asthenic (weakening) states, and to improve physical and mental working capacity. Picamilon was studied in a large number of scientific facilities within Russia. The total number of patients under observation was 984. Picamilon tablets were prescribed two to three times a day at a dose of 0.02 to 0.05 grams, and in a daily dose of 0.04 to 0.3 grams. Courses of treatment lasted from two weeks to one-and-a-half months.
The effectiveness of treatment was assessed by clinical and laboratory tests. Cerebral blood movements were evaluated by objective methods, including echopulsography, echoencephalography, rheo- encephalography, ultrasonic scanning, biomicroscopy of the conjuctiva, and electroencephalography.
In patients with acute cerebrovascular disturbances, improvement occurred on the fourth or fifth day, when the severity of neurologic symptoms was reduced. Later, headache, dizziness, noise in the head and memory disorders were reduced, motor and speech disorders began to regress rapidly, sleep improved, and irritability, emotional stress and anxiety were reduced. The velocity of cerebral blood flow was increased.
Administration of Picamilon to patients suffering from the results of cerebrovascular disturbances (more than a month later) proved effective after the second or third day of treatment. The patients' emotional background, speech and memory were improved, and levels of enzyme activity (AST, ALT, LDH) and lactate concentration were restored to normal.
Scientists who studied the effects of GABA derivatives on the development of toxic cerebral edema (fluid on the brain) showed that Picamilon in specific doses prevented the development of edema.
In chronic cerebral insufficiency, Picamilon improved the mood and memory of the patients, reduced irritability and tearfulness, abolished autonomic vascular manifestations, and reduced metabolic disturbances. In patients with memory disorders (global amnesia), considerable improvement in memorization and recall was observed on the fifth to seventh day of treatment, and the patients were able to return to work.
In patients with astheno-neurotic anxiety and depression, activation of mental functions and motor activity was observed, including improved speed and quality of operative activity, concentration of attention and mood, relief of anxiety, improved working capacity, and so on. The use of Picamilon in depression, along with moderate doses of tricyclic antidepressants, enabled the doses of the latter to be reduced. In patients with alcoholism, Picamilon abolished many withdrawal symptoms, especially apathy, weariness and lethargy. The patients later become more tranquil, less fussy and anxious, and their working capacity improved. | Picamilon
Picamilon is a compound formed by reacting niacin with GABA. It was invented in Russia.[1] Picamilon is able to cross the blood-brain barrier[2] and activate GABA receptors, producing an anxiolytic response. The niacin also acts as a strong vasodialator, helping to improve awareness.
Studies from Russia demonstrate that Picamilon improves nervous control, recovery time after work, blood pressure and memory. The drug even shows benefits in treating brain trauma.
An essential role in the mechanism of action of Picamilon is its effect on nervous control of the cerebral circulation. It weakens changes in cerebral blood flow during the vasomotor reflex, considerably inhibits constrictor responses of vessels in the carotid and vertebrobasilar basins due to stimulation of afferent fibers of somatic nerves, and causes gradually developing inhibition of tonic and reflex activity in sympathetic nerves.
Neuropharmacological screening tests on Picamilon have demonstrated its tranquilizing properties in small doses. For instance, at a dose of l mg/kg, Picamilon prevents the negative consequences of emotional stress (in cats it normalizes the orienting reaction when disturbed by the response to rage and fear). Like diazepam, it has an inhibitory effect on motivated aggression, associated with fighting for territory in rats.
Investigation of Picamilon's effect on the threshold of "self-stimulation" showed that in higher doses (80 and 160 mg/kg), in contrast with small doses which have a tranquilizing effect, Picamilon lowered the "self-stimulation" threshold (like amphetamine), but at the same time reduced the number of self-stimulation. The stimulating action of the drug also has been shown in general anesthesia. For instance, at a dose of 100 mg/kg, Picamilon reduced by 1.7 times the duration of the sedative effect of hexobarbital sodium and reduced by half the duration of thiopental anesthesia.
Unlike tranquilizer drugs (chlorodiazepoxide, diazepam, relanium, phenazepam), Picamilon does not induce muscle relaxation, drowsiness or lethargy. Clinicians have stated that the drug closely resembles cavinton (the ethyl ester of apovincamic acid), but comparison of the properties of the two compounds showed that Picamilon is superior.
Picamilon produces no allergenic, teratogenic, embryotoxic or carcinogenic effects. On this basis, the pharmacological committee of the Ministry of the Health (Russia) recommended clinical trials of Picamilon for cerebrovascular disturbances, as a daytime tranquilizer, as a stimulant in depressive and asthenic (weakening) states, and to improve physical and mental working capacity. Picamilon was studied in a large number of scientific facilities within Russia. The total number of patients under observation was 984. Picamilon tablets were prescribed two to three times a day at a dose of 0.02 to 0.05 grams, and in a daily dose of 0.04 to 0.3 grams. Courses of treatment lasted from two weeks to one-and-a-half months.
The effectiveness of treatment was assessed by clinical and laboratory tests. Cerebral blood movements were evaluated by objective methods, including echopulsography, echoencephalography, rheo- encephalography, ultrasonic scanning, biomicroscopy of the conjuctiva, and electroencephalography.
In patients with acute cerebrovascular disturbances, improvement occurred on the fourth or fifth day, when the severity of neurologic symptoms was reduced. Later, headache, dizziness, noise in the head and memory disorders were reduced, motor and speech disorders began to regress rapidly, sleep improved, and irritability, emotional stress and anxiety were reduced. The velocity of cerebral blood flow was increased.
Administration of Picamilon to patients suffering from the results of cerebrovascular disturbances (more than a month later) proved effective after the second or third day of treatment. The patients' emotional background, speech and memory were improved, and levels of enzyme activity (AST, ALT, LDH) and lactate concentration were restored to normal.
Scientists who studied the effects of GABA derivatives on the development of toxic cerebral edema (fluid on the brain) showed that Picamilon in specific doses prevented the development of edema.
In chronic cerebral insufficiency, Picamilon improved the mood and memory of the patients, reduced irritability and tearfulness, abolished autonomic vascular manifestations, and reduced metabolic disturbances. In patients with memory disorders (global amnesia), considerable improvement in memorization and recall was observed on the fifth to seventh day of treatment, and the patients were able to return to work.
In patients with astheno-neurotic anxiety and depression, activation of mental functions and motor activity was observed, including improved speed and quality of operative activity, concentration of attention and mood, relief of anxiety, improved working capacity, and so on. The use of Picamilon in depression, along with moderate doses of tricyclic antidepressants, enabled the doses of the latter to be reduced. In patients with alcoholism, Picamilon abolished many withdrawal symptoms, especially apathy, weariness and lethargy. The patients later become more tranquil, less fussy and anxious, and their working capacity improved. | https://www.wikidoc.org/index.php/Picamilon | |
dd66c2a31bc79174070b6de2a162a1bff68e64d6 | wikidoc | Picenadol | Picenadol
Picenadol (LY-150720) is a 4-phenylpiperidine derivative that is an opioid analgesic drug.
Picenadol is an effective analgesic with similar efficacy to pethidine (meperidine). It has been investigated for some applications such as obstetrics and dentistry, but never commercialised.
It is unusual in that one enantiomer is a pure μ-opioid agonist, while the other is an antagonist. The (3R,4R) isomer is the agonist, while (3S,4S) is antagonist. This means that the racemic mix of the two enantiomers is a mixed agonist-antagonist, with relatively low abuse potential, and little of the κ-opioid activity that tends to cause problems with other opioid mixed agonist-antagonists such as pentazocine. | Picenadol
Picenadol (LY-150720) is a 4-phenylpiperidine derivative that is an opioid analgesic drug.
Picenadol is an effective analgesic with similar efficacy to pethidine (meperidine). It has been investigated for some applications such as obstetrics[1] and dentistry,[2] but never commercialised.
It is unusual in that one enantiomer is a pure μ-opioid agonist, while the other is an antagonist.[3] The (3R,4R) isomer is the agonist, while (3S,4S) is antagonist.[4] This means that the racemic mix of the two enantiomers is a mixed agonist-antagonist, with relatively low abuse potential, and little of the κ-opioid activity that tends to cause problems with other opioid mixed agonist-antagonists such as pentazocine.[5] | https://www.wikidoc.org/index.php/Picenadol | |
4a720c09d80e73dfc9ee81c1418ffb798b4f1f09 | wikidoc | Pinazepam | Pinazepam
# Overview
Pinazepam (marketed under the brand name Domar and Duna) is a drug that is a benzodiazepine. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.
Pinazepam and its metabolite N-desmethyldiazepam (nordiazepam, nordazepam) are transferred to the developing fetus in utero, but the plasma drug level in the mother is usually significantly higher than in the fetus.
Pinazepam differs from other benzodiazepines in that it has a propargyl group at the N-1 position of the benzodiazepine structure. It is less toxic than diazepam and in animal studies it appears to produce anxiolytic and anti-agitation properties with limited hypnotic and motor coordination impairing properties. Pinazepam is rapidly absorbed after oral administration. The main active metabolites of pinazepam are depropargylpinazepam (N-desmethyldiazepam, nordazepam) and oxazepam. In humans pinazepam acts as a pure anxiolytic agent in that it does not possess to any significant degree the other pharmacological characteristics of benzodiazepines. Its lack of intellectual, motor and hypnotic impairing effects makes it more appropriate than other benzodiazepines for day time use. The elimination half-life is longer in the elderly. | Pinazepam
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pinazepam (marketed under the brand name Domar and Duna) is a drug that is a benzodiazepine.[1] It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.
Pinazepam and its metabolite N-desmethyldiazepam (nordiazepam, nordazepam) are transferred to the developing fetus in utero, but the plasma drug level in the mother is usually significantly higher than in the fetus.[2]
Pinazepam differs from other benzodiazepines in that it has a propargyl group at the N-1 position of the benzodiazepine structure. It is less toxic than diazepam and in animal studies it appears to produce anxiolytic and anti-agitation properties with limited hypnotic and motor coordination impairing properties. Pinazepam is rapidly absorbed after oral administration. The main active metabolites of pinazepam are depropargylpinazepam (N-desmethyldiazepam, nordazepam) and oxazepam. In humans pinazepam acts as a pure anxiolytic agent in that it does not possess to any significant degree the other pharmacological characteristics of benzodiazepines. Its lack of intellectual, motor and hypnotic impairing effects makes it more appropriate than other benzodiazepines for day time use.[3][4][5] The elimination half-life is longer in the elderly.[6] | https://www.wikidoc.org/index.php/Pinazepam | |
781cf7bfbbcba5345102b5c5e89d8bf0baadf8a1 | wikidoc | Pipe tool | Pipe tool
A pipe tool is any of a variety of small gadgets designed to aid in packing, smoking, and emptying tobacco pipes.
A typical pipe tool consists of a reamer, a tamper, and a scraper:
- The reamer is a narrow rod or pin that can be used to loosen tobacco or empty a pipe.
- The scraper is a flat instrument shaped like a dull pen-knife blade or a flattened spoon, used to scrape ash and unburned tobacco off the sides of a pipe, and to reduce the cake of ash on the inside of the bowl.
- The tamper is a blunt instrument, either a simple dowel or shaped like the top of a nail, with a flat end for tamping down the tobacco when the bowl is being packed, and for crushing the ash together to aid relighting.
mk:Алатка за луле | Pipe tool
A pipe tool is any of a variety of small gadgets designed to aid in packing, smoking, and emptying tobacco pipes.
A typical pipe tool consists of a reamer, a tamper, and a scraper:
- The reamer is a narrow rod or pin that can be used to loosen tobacco or empty a pipe.
- The scraper is a flat instrument shaped like a dull pen-knife blade or a flattened spoon, used to scrape ash and unburned tobacco off the sides of a pipe, and to reduce the cake of ash on the inside of the bowl.
- The tamper is a blunt instrument, either a simple dowel or shaped like the top of a nail, with a flat end for tamping down the tobacco when the bowl is being packed, and for crushing the ash together to aid relighting.
mk:Алатка за луле | https://www.wikidoc.org/index.php/Pipe_tool | |
4f490986d23a67dbda4ab9fb48bbec227a5bca04 | wikidoc | Pipradrol | Pipradrol
# Overview
Pipradrol (Meretran) is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate. Pipradrol is still used in some European countries, and even rarely in the USA.
Pipradrol was developed in the 1950s and found use initially for treating obesity. It was subsequently used for the treatment of a variety of other conditions such as narcolepsy, ADHD, and most particularly for counteracting the symptoms of senile dementia, this being the only application for which it is still used medically. Pipradrol proved useful for these applications as its relatively mild stimulant effects gave it a good safety profile compared to stronger stimulants. It was also trialled as an adjutant treatment for depression and schizophrenia although it was never widely used for these purposes.
Pipradrol was made illegal in many countries in the late 1970s, at the same time as many other drugs which had a history of abuse. The relatively mild stimulant effects of pipradrol meant that it was scheduled under the less restrictive classes in most countries (i.e. Class C in United Kingdom and New Zealand) but was still considered of sufficient abuse potential to be made an illegal drug. It is now an obscure compound that is virtually unknown as an illicit drug of abuse, but is still used for some scientific research, often as a comparison drug for testing other stimulants against.
Dosage is between 0.5 and 4 milligrams per day, typically taken as a single dose in the morning as the long duration of effects of pipradrol (up to 12 hours) means insomnia can be a problem especially if it is used at higher doses or taken too late in the day.
Common side effects include insomnia, anorexia, tachycardia, anxiety. Rarer side effects include dry mouth, tremor, hypertension, euphoria, depression, and very rarely psychosis or convulsions. | Pipradrol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pipradrol (Meretran) is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate. Pipradrol is still used in some European countries, and even rarely in the USA.[1]
Pipradrol was developed in the 1950s and found use initially for treating obesity.[2] It was subsequently used for the treatment of a variety of other conditions such as narcolepsy, ADHD, and most particularly for counteracting the symptoms of senile dementia, this being the only application for which it is still used medically. Pipradrol proved useful for these applications as its relatively mild stimulant effects gave it a good safety profile compared to stronger stimulants. It was also trialled as an adjutant treatment for depression and schizophrenia although it was never widely used for these purposes.
Pipradrol was made illegal in many countries in the late 1970s, at the same time as many other drugs which had a history of abuse. The relatively mild stimulant effects of pipradrol meant that it was scheduled under the less restrictive classes in most countries (i.e. Class C in United Kingdom and New Zealand) but was still considered of sufficient abuse potential to be made an illegal drug. It is now an obscure compound that is virtually unknown as an illicit drug of abuse, but is still used for some scientific research, often as a comparison drug for testing other stimulants against.
Dosage is between 0.5 and 4 milligrams per day, typically taken as a single dose in the morning as the long duration of effects of pipradrol (up to 12 hours) means insomnia can be a problem especially if it is used at higher doses or taken too late in the day.
Common side effects include insomnia, anorexia, tachycardia, anxiety. Rarer side effects include dry mouth, tremor, hypertension, euphoria, depression, and very rarely psychosis or convulsions. | https://www.wikidoc.org/index.php/Pipradrol | |
8059590547afdcc2cc4e738e0d2d55921c6ad13a | wikidoc | Piracetam | Piracetam
# Overview
Piracetam (brand name: Nootropil®, Myocalm®) is a nootropic. It is a cerebral function regulating drug which, it is claimed, is able to enhance cognition and memory, slow down brain aging, increase blood flow and oxygen to the brain, aid stroke recovery, and improve Alzheimer's, Down's Syndrome, dementia, and dyslexia, among others. Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). Piracetam is a cyclic derivative of GABA. It is one of the racetams. Though largely ignored in the United States, piracetam is commonly prescribed in Europe for a variety of conditions. However, in some places, due to its non-toxic nature and its general health benefits it is seen more as a food supplement than as a drug. One of its general health effects is said to be toning of damaged nerves and muscles (although this is scientifically unverified). It is safe for use by itself as a non-prescription drug in a reasonably healthy person.
# Effects
Several meta-reviews of literature on piracetam indicate that piracetam increases performance on a variety of cognitive tasks among dyslexic children, though this may reflect its enhancement of cross-hemispheric communication and of cognitive function in general, rather than a specific improvement in whatever causes dyslexia. Piracetam also seems to inhibit brain damage caused by a variety of factors including hypoxia and excessive alcohol consumption.
Piracetam has been studied in an extensive number of clinical experiments, and has shown positive results in the treatment of post-stroke aphasia, epilepsy, cognitive decline following heart and brain surgery, dementia, and myoclonus.
Piracetam appears to increase communication between the two hemispheres of the brain, and increases activity of the corpus callosum.
# Mechanisms of action
The mechanism of action of piracetam is not known, although it is hypothesized to act on ion channels or ion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity. It has been found to increase blood flow and oxygen consumption in parts of the brain.
Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes. Furthermore, Piracetam may have an effect on NMDA glutamate receptors which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Ca2+, K+). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brain. Piracetam appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria. It also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.
# History
Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea. The drug was the first of the so-called nootropics ("smart drugs" or "cognitive enhancers"), that is, substances which purportedly enhance mental performance. The term nootropic was coined by Giurgea. Nootropil was launched clinically by UCB in the early 1970s and remains an important product of that company in Europe.
# Approval and usage
Piracetam is primarily used in Europe, Asia, South America and the US. Piracetam is legal to import into the United Kingdom and the United States for personal use with or without prescription as with other prescription-only drugs. As of June of 2006, piracetam is sold in the United States as a dietary supplement. It has become popular as a cognitive enhancement drug among students, who often buy it in bulk as a powder and then consume it with orange juice to mask the strong, bitter taste. A two week regimen of piracetam was found to enhance verbal memory in healthy college students in a double-blind, placebo-controlled study. It is used by parents as a treatment for childhood autism, though no study has yet produced results which would support such a use.
## Aging
Piracetam appears to reverse the effects of aging in the brains of mice.
Piracetam appears to reduce levels of lipofuscin in the rat brain. (Lipofuscin accumulation is common symptom of aging and alcoholism).
## Alcoholism
Piracetam appears to be effective in treating alcoholism or its symptoms.
## Alzheimer's and senile dementia
Piracetam appears to be effective for improving cognition in Alzheimer's disease and senile dementia patients.
## Clotting, coagulation, vasospastic disorders
Piracetam is useful as a long term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon and deep vein thrombosis It is an extremely safe anti-thrombotic agent which operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood cell deformability. Because traditional anti-thrombotic drugs operate through the separate mechanism of inhibiting clotting factors, co-adminsitration of piracetam has been shown to highly complement the efficacy and safety of traditional Warfarin/Heparin anti-coagulation therapy. The most effective treatment range for this use is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart. Piracetam is currently being investigated as a complement or alternative to Warfarin as a safe and effective long term treatment for recurring deep vein thrombosis.
## Stroke, ischemia and symptoms
Piracetam has been found to improve cognition after stroke, and reduce symptoms, such as aphasia. It also improves cognition in cases of chronic ischemia.
## Dyspraxia and Dysgraphia
Due to its supposed effect on nerves and muscles it is sometimes prescribed as an aid to Muscle or dexterity training. There has not been a specific study as to whether it is beneficial in this aspect. Vinpocetine, another purported nootropic with which piracetam is indirectly synergesic, is confirmed to help with these conditons to a certain degree.
## Schizophrenia
Piracetam improves cognitive performance of schizophrenics as it does with non-schizophrenics, but does not improve or worsen the chronic schizophrenia disease state.
# Dosage
Piracetam is usually supplied in 800 mg tablets or capsules. Some bulk or nutritional suppliers supply it in a powder form. The recommended dosage varies based on the indication, usually ranging from 1.6-9.6 grams daily (2-12 pills daily). Some people report faster results when taking 1-2 pills every hour for 4-6 hours or taking 4-8 pills at once for the first few days to notice an effect.
For blood coagulation, clotting, and vasospastic disorders such as Raynaud's phenomenon or deep vein thrombosis, the most effective treatment range is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.
It has been studied up to 45 grams daily without major side effects.
It has no known LD-50 in humans when taken orally.
# Contraindications
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute), hepatic (liver) impairment and to those under 16 years of age. It is also contraindicated in patients with cerebral haemorrhage and in those with hypersensitivity to piracetam, other pyrrolidone derivatives or any of the excipients.
# Special warnings and precautions for use
Due to the effect of piracetam on platelet aggregation, caution is recommended in patients with underlying disorders of haemostasis, major surgery or severe haemorrhage.
Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
As piracetam is almost exclusively excreted by the kidneys caution should be exercised in treating patients with known renal impairment. In renally impaired and elderly patients, an increase in terminal half-life is directly related to renal function as measured by creatinine clearance. Dosage adjustment is therefore required in those with mild to moderate renal impairment and elderly patients with diminished renal function.
# Side effects
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient." A large-scale, 12-week trial of high-dose piracetam found no adverse effects occurred in the group taking piracetam as compared to the placebo group. Many other studies have likewise found piracetam to be well-tolerated.
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, and tremor - are occasionally reported.. Such symptoms seem more likely reported in connection with caffeine consumption (coffee), or with monosodium glutamate (a common additive in many processed foods). Effects can be reduced with magnesium supplements. Headache from use of piracetam may be alleviated by coadministration of an acetylcholine biosynthetic precursor, or a drug with cholinergic effects, such as choline bitarate, choline citrate, lecithin, cyprodenate or centrophenoxine. | Piracetam
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Piracetam (brand name: Nootropil®, Myocalm®) is a nootropic. It is a cerebral function regulating drug which, it is claimed, is able to enhance cognition and memory, slow down brain aging, increase blood flow and oxygen to the brain, aid stroke recovery, and improve Alzheimer's, Down's Syndrome, dementia, and dyslexia, among others.[1] Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). Piracetam is a cyclic derivative of GABA. It is one of the racetams. Though largely ignored in the United States, piracetam is commonly prescribed in Europe for a variety of conditions. However, in some places, due to its non-toxic nature and its general health benefits it is seen more as a food supplement than as a drug. One of its general health effects is said to be toning of damaged nerves and muscles (although this is scientifically unverified). It is safe for use by itself as a non-prescription drug in a reasonably healthy person.
# Effects
Several meta-reviews of literature on piracetam indicate that piracetam increases performance on a variety of cognitive tasks among dyslexic children, though this may reflect its enhancement of cross-hemispheric communication and of cognitive function in general, rather than a specific improvement in whatever causes dyslexia. Piracetam also seems to inhibit brain damage caused by a variety of factors including hypoxia and excessive alcohol consumption.[2][3]
Piracetam has been studied in an extensive number of clinical experiments, and has shown positive results in the treatment of post-stroke aphasia, epilepsy, cognitive decline following heart and brain surgery, dementia,[4] and myoclonus.[5][6]
Piracetam appears to increase communication between the two hemispheres of the brain, and increases activity of the corpus callosum.[7][8][9]
# Mechanisms of action
The mechanism of action of piracetam is not known, although it is hypothesized to act on ion channels or ion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity.[10] It has been found to increase blood flow and oxygen consumption in parts of the brain.[11]
Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes.[12] Furthermore, Piracetam may have an effect on NMDA glutamate receptors which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability.[12][13] Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Ca2+, K+).[10] It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brain. [14][15] Piracetam appears to increase the synthesis of cytochrome b5[16], which is a part of the electron transport mechanism in mitochondria. It also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle. [17]
# History
Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea. The drug was the first of the so-called nootropics ("smart drugs" or "cognitive enhancers"), that is, substances which purportedly enhance mental performance. The term nootropic was coined by Giurgea. Nootropil was launched clinically by UCB in the early 1970s and remains an important product of that company in Europe.
# Approval and usage
Piracetam is primarily used in Europe, Asia, South America and the US. Piracetam is legal to import into the United Kingdom and the United States for personal use with or without prescription as with other prescription-only drugs[citation needed]. As of June of 2006, piracetam is sold in the United States as a dietary supplement. It has become popular as a cognitive enhancement drug among students, who often buy it in bulk as a powder and then consume it with orange juice to mask the strong, bitter taste. A two week regimen of piracetam was found to enhance verbal memory in healthy college students in a double-blind, placebo-controlled study.[18] It is used by parents as a treatment for childhood autism, though no study has yet produced results which would support such a use.
## Aging
Piracetam appears to reverse the effects of aging in the brains of mice.[19][20]
Piracetam appears to reduce levels of lipofuscin in the rat brain. [21] (Lipofuscin accumulation is common symptom of aging and alcoholism).
## Alcoholism
Piracetam appears to be effective in treating alcoholism or its symptoms. [22]
[23]
[24]
[25]
[26]
[27]
## Alzheimer's and senile dementia
Piracetam appears to be effective for improving cognition in Alzheimer's disease and senile dementia patients.
[28]
[29]
[30]
[31]
[32]
## Clotting, coagulation, vasospastic disorders
Piracetam is useful as a long term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon[33] and deep vein thrombosis[12][34] It is an extremely safe anti-thrombotic agent which operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood cell deformability.[12] Because traditional anti-thrombotic drugs operate through the separate mechanism of inhibiting clotting factors, co-adminsitration of piracetam has been shown to highly complement the efficacy and safety of traditional Warfarin/Heparin anti-coagulation therapy.[35] The most effective treatment range for this use is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.[34] Piracetam is currently being investigated as a complement or alternative to Warfarin as a safe and effective long term treatment for recurring deep vein thrombosis.[34]
## Stroke, ischemia and symptoms
Piracetam has been found to improve cognition after stroke, and reduce symptoms, such as aphasia[36]. It also improves cognition in cases of chronic ischemia.
[37]
[38]
## Dyspraxia and Dysgraphia
Due to its supposed effect on nerves and muscles it is sometimes prescribed as an aid to Muscle or dexterity training. There has not been a specific study as to whether it is beneficial in this aspect. Vinpocetine, another purported nootropic with which piracetam is indirectly synergesic, is confirmed to help with these conditons to a certain degree.
## Schizophrenia
Piracetam improves cognitive performance of schizophrenics as it does with non-schizophrenics, but does not improve or worsen the chronic schizophrenia disease state.[2]
# Dosage
Piracetam is usually supplied in 800 mg tablets or capsules. Some bulk or nutritional suppliers supply it in a powder form. The recommended dosage varies based on the indication, usually ranging from 1.6-9.6 grams daily (2-12 pills daily). Some people report faster results when taking 1-2 pills every hour for 4-6 hours or taking 4-8 pills at once for the first few days to notice an effect.
For blood coagulation, clotting, and vasospastic disorders such as Raynaud's phenomenon or deep vein thrombosis, the most effective treatment range is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.[33][12][34]
It has been studied up to 45 grams daily without major side effects.[citation needed]
It has no known LD-50 in humans when taken orally.[10]
# Contraindications
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute), hepatic (liver) impairment and to those under 16 years of age. It is also contraindicated in patients with cerebral haemorrhage and in those with hypersensitivity to piracetam, other pyrrolidone derivatives or any of the excipients.
# Special warnings and precautions for use
Due to the effect of piracetam on platelet aggregation, caution is recommended in patients with underlying disorders of haemostasis, major surgery or severe haemorrhage.
Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
As piracetam is almost exclusively excreted by the kidneys caution should be exercised in treating patients with known renal impairment. In renally impaired and elderly patients, an increase in terminal half-life is directly related to renal function as measured by creatinine clearance. Dosage adjustment is therefore required in those with mild to moderate renal impairment and elderly patients with diminished renal function.
# Side effects
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient."[39] A large-scale, 12-week trial of high-dose piracetam found no adverse effects occurred in the group taking piracetam as compared to the placebo group.[40] Many other studies have likewise found piracetam to be well-tolerated.[41][42][39]
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, and tremor - are occasionally reported.[43][44]. Such symptoms seem more likely reported in connection with caffeine consumption (coffee), or with monosodium glutamate (a common additive in many processed foods). Effects can be reduced with magnesium supplements. Headache from use of piracetam may be alleviated by coadministration of an acetylcholine biosynthetic precursor, or a drug with cholinergic effects, such as choline bitarate, choline citrate, lecithin, cyprodenate or centrophenoxine.[citation needed] | https://www.wikidoc.org/index.php/Piracetam | |
6eeeb7ea092cba558d94e4a610c7df8c2d5218cc | wikidoc | Piribedil | Piribedil
# Overview
Piribedil is a piperazine dopamine agonist; and marketed as TRIVASTAL Retard 50.
Trivastal retard 50 is also distributed as:
Trastal, Trivastal 50 retard, Trivastal 50mg LP, Trivastan ritardo and Pronoran.
- Official site
# Composition:
Piribedil 50 mg per tablet - sustained-release.
# Indications:
- Treatment of Parkinson's disease, either as monotherapy (without L-dopa) or in combination with L-dopa therapy, in the early stages as well as in the advanced stages.
- Treatment of pathological cognitive deficits in the elderly (impaired attention, memory, etc). Treatment of dizziness in the elderly.
- Treatment of Retinal ischemic manifestations. Adjuvant treatment in intermittent claudication due to peripheral occlusive arterial disease of the lower limbs (stage 2).
- (off label) anhedonia and treatment-resistant depression in unipolar and bipolar depressives
# Dosage:
In Parkinson's disease: administration of Trivastal retard 50 should be initiated with 1 tablet daily during the first week. Dosage should then be gradually increased every week until achieving the optimal therapeutic dose:
as monotherapy: 3 to 5 tablets in 3 to 5 divided doses daily.
In combination with L-dopa therapy:
1 to 3 tablets daily. In other indications: 1 tablet daily at the end of the main meal. In severe cases: 2 tablets daily as 2 divided doses.
Trivastal retard 50 is a nonergot dopamine agonist, selective for D2 and D3 dopamine receptors subtypes at the cerebral and at the peripheral level.
Cardiogenic shock. Acute phase of myocardial infarction.
# Adverse:
rare side effects: minor gastrointestinal disorders (nausea, vomiting, flatulence) in predisposed individuals, or when taken between meals. They may resolve with the following: individual dosage adjustment, and/or addition of domperidone. Orthostatic hypotension or drowsiness may occur, particularly in predisposed individuals (underlying condition or causative illness).
Dopaminergic antagonists.
# Overdosage:
At very high doses, Trivastal retard 50 has an emetic action on the CTZ (chemoreceptive trigger zone). Tablets will thus be rapidly rejected, which explains why no data are currently available concerning the risk of overdosage. | Piribedil
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Piribedil is a piperazine dopamine agonist; and marketed as TRIVASTAL Retard 50.
Trivastal retard 50 is also distributed as:
Trastal, Trivastal 50 retard, Trivastal 50mg LP, Trivastan ritardo and Pronoran.
- Official site
# Composition:
Piribedil 50 mg per tablet - sustained-release.
# Indications:
- Treatment of Parkinson's disease, either as monotherapy (without L-dopa) or in combination with L-dopa therapy, in the early stages as well as in the advanced stages.
- Treatment of pathological cognitive deficits in the elderly (impaired attention, memory, etc). Treatment of dizziness in the elderly.
- Treatment of Retinal ischemic manifestations. Adjuvant treatment in intermittent claudication due to peripheral occlusive arterial disease of the lower limbs (stage 2).
- (off label) anhedonia and treatment-resistant depression in unipolar and bipolar depressives
# Dosage:
In Parkinson's disease: administration of Trivastal retard 50 should be initiated with 1 tablet daily during the first week. Dosage should then be gradually increased every week until achieving the optimal therapeutic dose:
as monotherapy: 3 to 5 tablets in 3 to 5 divided doses daily.
In combination with L-dopa therapy:
1 to 3 tablets daily. In other indications: 1 tablet daily at the end of the main meal. In severe cases: 2 tablets daily as 2 divided doses.
Trivastal retard 50 is a nonergot dopamine agonist, selective for D2 and D3 dopamine receptors subtypes at the cerebral and at the peripheral level.
Cardiogenic shock. Acute phase of myocardial infarction.
# Adverse:
rare side effects: minor gastrointestinal disorders (nausea, vomiting, flatulence) in predisposed individuals, or when taken between meals. They may resolve with the following: individual dosage adjustment, and/or addition of domperidone. Orthostatic hypotension or drowsiness may occur, particularly in predisposed individuals (underlying condition or causative illness).
Dopaminergic antagonists.
# Overdosage:
At very high doses, Trivastal retard 50 has an emetic action on the CTZ (chemoreceptive trigger zone). Tablets will thus be rapidly rejected, which explains why no data are currently available concerning the risk of overdosage.
Template:Drug-stub
Template:Dopamine agonists | https://www.wikidoc.org/index.php/Piribedil | |
379113ff0f3a5dca1b5536a5e7104170c9b0034e | wikidoc | Pizotifen | Pizotifen
For patient information about Pizotifen, click here
# Overview
Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches.
# Mechanism
Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity.
# Side effects
Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it may cause nausea or dizziness. In rare cases, anxiety, aggression and depression may also occur. Rare side effects include confusion, stomach pain, vision changes, mood changes,and sexual dysfunction.
# Contraindications
Caution is required in patients having closed angle glaucoma and in patients with a predisposition to urinary retention as the drug exhibits a relatively small anticholinergic effect. Dose adjustment is required in patients having renal insufficiency. Hepatic injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment.Caution is advised in patients having a history of epilepsy.
Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decrease have been reported following abrupt cessation of pizotifen.
Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components, also Pizotifen is contraindicated in gastric outlet obstruction, pregnancy, angle-closure glaucoma and difficulty urinating.
# Uses
The main medical use for Pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propanolol, valproic acid and amitryptyline. While pizotifen is reasonably effective, its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective. It is not effective in relieving migraine attacks once in progress.
Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia. Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose in a similar manner to the closely related antihistamine/antiserotonin drug cyproheptadine.
# Dose
Typically adult does is 1.5mg at night or 500 micrograms 3 times daily, adjusted according to response. Max single does 3mg, max daily dose 4.5mg.
Child over 2 years and up, up to 1.5mg daily in divided dose; max single dose at night 1mg. | Pizotifen
Template:Pizotifen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]
For patient information about Pizotifen, click here
# Overview
Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches.[1]
# Mechanism
Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity.[2]
# Side effects
Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.[3] Occasionally it may cause nausea or dizziness. In rare cases, anxiety, aggression and depression may also occur. Rare side effects include confusion, stomach pain, vision changes, mood changes,and sexual dysfunction.
# Contraindications
Caution is required in patients having closed angle glaucoma and in patients with a predisposition to urinary retention as the drug exhibits a relatively small anticholinergic effect. Dose adjustment is required in patients having renal insufficiency. Hepatic injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment.Caution is advised in patients having a history of epilepsy.
Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decrease have been reported following abrupt cessation of pizotifen.[4]
Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components, also Pizotifen is contraindicated in gastric outlet obstruction, pregnancy, angle-closure glaucoma and difficulty urinating.[5]
# Uses
The main medical use for Pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propanolol, valproic acid and amitryptyline. While pizotifen is reasonably effective,[6] its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective.[7] It is not effective in relieving migraine attacks once in progress.
Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia.[8][9] Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose[10] in a similar manner to the closely related antihistamine/antiserotonin drug cyproheptadine.
# Dose
Typically adult does is 1.5mg at night or 500 micrograms 3 times daily, adjusted according to response. Max single does 3mg, max daily dose 4.5mg.
Child over 2 years and up, up to 1.5mg daily in divided dose; max single dose at night 1mg. | https://www.wikidoc.org/index.php/Pizotifen | |
00994a3f94a50dee8ca6b1df36befdbf9ff5d4f6 | wikidoc | Plectasin | Plectasin
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 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.
Plectasin is a new antibiotic found by Novozymes in the mushroom Pseudoplectania nigrella. Plectasin belongs to the antimicrobial peptide class called Defensins. Tests on mice have shown promising results that multiresistant bacteria have problems mutating resistance against Plectasin, however development and registration of a product are still 7 to 10 years off. | Plectasin
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Plectasin is a new antibiotic found by Novozymes in the mushroom Pseudoplectania nigrella. Plectasin belongs to the antimicrobial peptide class called Defensins. Tests on mice have shown promising results that multiresistant bacteria have problems mutating resistance against Plectasin, however development and registration of a product are still 7 to 10 years off.
# External links
- Novozymes, company press release on Plectasin
- bio.com, article on the findings
Template:SIB
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Plectasin | |
0af115f11c50e5348bb437b6e27a463807633806 | wikidoc | Podofilox | Podofilox
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Podofilox is an antimitotic agent that is FDA approved for the treatment of anogenital warts. Common adverse reactions include pruritus, superficial ulcer of skin, pain, burning sensation, Inflammatory disorder.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Anogenital warts
- Condylox Gel 0.5% is indicated for the topical treatment of anogenital warts (external genital warts and perianal warts). This product is not indicated in the treatment of mucous membrane warts.
- Dosing information:
- Condyloma acuminatum, External: apply 0.5% solution or gel TOPICALLY every 12 hours in the morning and evening for 3 days, then withhold for 4 days; repeat cycle up to 4 times.
- Condyloma acuminatum, perianal: apply 0.5% gel TOPICALLY for 3 days, then withhold for 4 days, repeat cycle up to 4 times
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Podofilox in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Podofilox in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Podofilox FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Podofilox in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Podofilox in pediatric patients.
# Contraindications
- Condylox Gel 0.5% is contraindicated for patients who develop hypersensitivity or intolerance to any components of the formulation.
# Warnings
- Correct diagnosis of the lesions to be treated is essential. See the Diagnosis subsection of the INDICATIONS AND USAGE section. Condylox Gel 0.5% is intended for cutaneous use only. Avoid contact with the eyes. If contact with the eyes occurs, patients should immediately flush the eyes with copious quantities of water and seek medical advice.
- Drug Product is Flammable.
- Keep Away From Open Flame.
PRECAUTIONS
General
- Data are not available on the safe and effective use of this product for treatment of warts occurring on mucous membranes of the genital area (including the urethra, rectum and vagina). The recommended method of application, frequency of application, and duration of usage should not be exceeded.
# Adverse Reactions
## Clinical Trials Experience
- In clinical trials with Condylox Gel 0.5%, the following local adverse reactions were reported during the treatment of anogenital warts. The severity of local adverse reactions were predominantly mild or moderate and did not increase during the treatment period. Severe reactions were most frequent within the first 2 weeks of treatment.
- Adverse Reaction Mild Moderate Severe
- Inflammation 32.2% 30.4% 9.3%
- Burning 37.1% 25.9% 11.5%
- Erosion 27.0% 20.8% 8.9%
- Pain 23.7% 20.4% 11.5%
- Itching 32.2% 16.0% 7.8%
- Bleeding 19.2% 3.0% 0.7%
- Other local adverse reactions reported included stinging (7%), and erythema (5%); less commonly reported local adverse events included desquamation, scabbing, discoloration, tenderness, dryness, crusting, fissures, soreness, ulceration, swelling/edema, tingling, rash, and blisters.
- The most common systemic adverse event reported during the clinical studies was headache (7%).
## Postmarketing Experience
There is limited information regarding Podofilox Postmarketing Experience in the drug label.
# Drug Interactions
There is limited information regarding Podofilox Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C: 0.5% podofilox solution was not teratogenic in the rabbit following topical application of up to 0.21 mg/kg (2.85 mg/m2, approximately 2 times the maximum human dose) once daily for 13 days. The scientific literature contains references that podofilox is embryotoxic in rats when administered intraperitoneally at a dose of 5 mg/kg (29.5 mg/m2, approximately 19 times the recommended maximum human dose.)9 Teratogenicity and embryotoxicity have not been studied with intravaginal application. Many antimitotic drug products are known to be embryotoxic. There are no adequate and well-controlled studies in pregnant women. Condylox Gel 0.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Podofilox in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Podofilox during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from podofilox, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
There is no FDA guidance on the use of Podofilox in geriatric settings.
### Gender
There is no FDA guidance on the use of Podofilox with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Podofilox with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Podofilox in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Podofilox in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Podofilox in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Podofilox in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- The prescriber should ensure that the patient is fully aware of the correct method of therapy and identify which specific warts should be treated.
- Apply twice daily for 3 consecutive days, then discontinue for 4 consecutive days. This one week cycle of treatment may be repeated until there is no visible wart tissue or for a maximum of four cycles. If there is incomplete response after four treatment cycles, discontinue treatment and consider alternative treatment. Safety and effectiveness of more than four treatment cycles has not been established. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption.
- Condylox Gel 0.5% should be applied to the warts with the applicator tip or finger. Application on the surrounding normal tissue should be minimized. Treatment should be limited to 10 cm2 or less of wart tissue and to no more than 0.5 g of the gel per day.
- Care should be taken to allow the gel to dry before allowing the return of opposing skin surfaces to their normal positions. Patients should be instructed to wash their hands thoroughly before and after each application.
### Monitoring
There is limited information regarding Podofilox Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Podofilox and IV administrations.
# Overdosage
- Topically applied podofilox may be absorbed systemically. Toxicity reported following systemic administration of podofilox in investigational use for cancer treatment included: nausea, vomiting, fever, diarrhea, bone marrow depression, and oral ulcers. Following 5 to 10 daily intravenous doses of 0.5 to 1 mg/kg/day, significant hematological toxicity occurred but was reversible.10 Other toxicities occurred at lower doses. Toxicity reported following systemic administration of podophyllum resin included: nausea, vomiting, fever, diarrhea, peripheral neuropathy, altered mental status, lethargy, coma, tachypnea, respiratory failure, leukocytosis, pancytosis, hematuria, renal failure and seizures.11 Treatment of topical overdosage should include washing the skin free of any remaining drug and symptomatic and supportive therapy.
# Pharmacology
## Mechanism of Action
- Treatment of anogenital warts with podofilox results in necrosis of visible wart tissue. The exact mechanism of action is unknown.
## Structure
- Podofilox is an antimitotic drug which can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (e.g. species of Juniperus and Podophyllum). Condylox Gel 0.5% is formulated for topical administration. Each gram of gel contains 5 mg of podofilox in a buffered alcoholic gel containing alcohol, glycerin, lactic acid, hydroxypropyl cellulose, sodium lactate, and butylated hydroxytoluene.
- Podofilox has a molecular weight of 414.4 daltons, and is soluble in alcohol and sparingly soluble in water. Its chemical name is -5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl) furonaphtho--1,3-dioxol-6(5aH)-one.
- Podofilox has the following structural formula:
## Pharmacodynamics
There is limited information regarding Podofilox Pharmacodynamics in the drug label.
## Pharmacokinetics
- In systemic absorption studies in 52 patients, topical application of 0.05 mL of an ethanolic solution containing 0.5% podofilox to external genitalia did not result in detectable serum levels. Applications of 0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application. The elimination half-life ranged from 1.0 to 4.5 hours. The drug was not found to accumulate after multiple treatments1.
## Nonclinical Toxicology
Carcinogenesis, Mutagenesis and Impairment of Fertility
- An 80-week carcinogenicity study in the mouse was performed using a 0.5% podofilox solution applied dermally at 0.04, 0.2 and 1.0 mg/kg/day. There were no differences between the podofilox treated mice at any dose level and vehicle control in the incidence of neoplasia. Published animal studies, in general, have not shown the drug substance, podofilox, to be carcinogenic.2,3,4,5,6 There are published reports that, in mouse studies, crude podophyllin resin (containing podofilox) applied topically to the cervix produced changes resembling carcinoma in situ.7 These changes were reversible at five weeks after cessation of treatment. In one reported experiment, epidermal carcinoma of the vagina and cervix was found in 1 out of 18 mice after 120 applications of podophyllin8 (the drug was applied twice weekly over a 15-month period).
- Podofilox was not mutagenic in the Ames plate reverse mutation assay at concentrations up to 5 mg/plate, with and without metabolic activation. No cell transformation related to potential oncogenicity was observed in BALB/3T3 cells after exposure to podofilox at concentrations up to 0.008 μg/mL, without metabolic activation and 12 μg/mL podofilox with metabolic activation. Results from the mouse micronucleus in vivo assay using podofilox 0.5% solution at doses up to 25 mg/kg (75 mg/m2), indicate that podofilox should be considered a potential clastogen (a chemical that induces disruption and breakage of chromosomes).
- Daily topical application of 0.5% podofilox solution at doses up to the equivalent of 0.2 mg/kg (1.18 mg/m2, approximately equivalent to the human daily dose) to rats throughout gametogenesis, mating, gestation, parturition and lactation for two generations demonstrated no impairment of fertility.
# Clinical Studies
- In the first multicenter clinical study in 326 patients with anogenital warts, Condylox Gel 0.5% and its vehicle were applied in a double-blind fashion to comparable patient groups. Of the 260 patients with efficacy data, 176 were treated with Condylox Gel 0.5%. Patients applied Condylox Gel 0.5% twice daily for three consecutive days followed by a 4 day “rest” period.
- At the end of 4 weeks, 38.4% of the patients had complete clearing of the wart tissue when treated with Condylox Gel 0.5%.
- In the second multicenter clinical trial in 108 evaluable patients with anogenital warts, Condylox (podofilox) Topical Solution 0.5% was compared with Condylox Gel 0.5% for efficacy. As in the first clinical trial, patients applied Condylox Gel 0.5% twice daily for three consecutive days followed by a four day “rest” period.
- Similar clearance rates were observed. At the end of 4 weeks, 25.6% of the patients had complete clearing of the wart tissue when treated with Condylox Gel 0.5%.
# How Supplied
- Condylox Gel 0.5% is supplied as 3.5 g of clear gel in aluminum tubes with an applicator tip. NDC 52544-045-13. Store at 20-25°C (68-77°F).
## Storage
- Avoid excessive heat. Do not freeze.
- Keep out of reach of children.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Information for Patients
- Patients using Condylox Gel 0.5% should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not intended to disclose all possible adverse or intended effects.
- This medication should be used only as directed by the health care provider. Patients should be instructed to wash their hands thoroughly before and after each application. It is for external use only. Avoid contact with the eyes.
- Patients should be advised not to use this medication for any disorder other than for which it was prescribed.
- Patients should report any signs of adverse reactions to the health care provider.
- If no improvement is observed after 4 weeks of treatment, discontinue the medication and consult the health care provider.
# Precautions with Alcohol
Alcohol-Podofilox interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Condylox
# Look-Alike Drug Names
There is limited information regarding Podofilox Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Podofilox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Podofilox is an antimitotic agent that is FDA approved for the treatment of anogenital warts. Common adverse reactions include pruritus, superficial ulcer of skin, pain, burning sensation, Inflammatory disorder.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Anogenital warts
- Condylox Gel 0.5% is indicated for the topical treatment of anogenital warts (external genital warts and perianal warts). This product is not indicated in the treatment of mucous membrane warts.
- Dosing information:
- Condyloma acuminatum, External: apply 0.5% solution or gel TOPICALLY every 12 hours in the morning and evening for 3 days, then withhold for 4 days; repeat cycle up to 4 times.
- Condyloma acuminatum, perianal: apply 0.5% gel TOPICALLY for 3 days, then withhold for 4 days, repeat cycle up to 4 times
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Podofilox in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Podofilox in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Podofilox FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Podofilox in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Podofilox in pediatric patients.
# Contraindications
- Condylox Gel 0.5% is contraindicated for patients who develop hypersensitivity or intolerance to any components of the formulation.
# Warnings
- Correct diagnosis of the lesions to be treated is essential. See the Diagnosis subsection of the INDICATIONS AND USAGE section. Condylox Gel 0.5% is intended for cutaneous use only. Avoid contact with the eyes. If contact with the eyes occurs, patients should immediately flush the eyes with copious quantities of water and seek medical advice.
- Drug Product is Flammable.
- Keep Away From Open Flame.
PRECAUTIONS
General
- Data are not available on the safe and effective use of this product for treatment of warts occurring on mucous membranes of the genital area (including the urethra, rectum and vagina). The recommended method of application, frequency of application, and duration of usage should not be exceeded.
# Adverse Reactions
## Clinical Trials Experience
- In clinical trials with Condylox Gel 0.5%, the following local adverse reactions were reported during the treatment of anogenital warts. The severity of local adverse reactions were predominantly mild or moderate and did not increase during the treatment period. Severe reactions were most frequent within the first 2 weeks of treatment.
- Adverse Reaction Mild Moderate Severe
- Inflammation 32.2% 30.4% 9.3%
- Burning 37.1% 25.9% 11.5%
- Erosion 27.0% 20.8% 8.9%
- Pain 23.7% 20.4% 11.5%
- Itching 32.2% 16.0% 7.8%
- Bleeding 19.2% 3.0% 0.7%
- Other local adverse reactions reported included stinging (7%), and erythema (5%); less commonly reported local adverse events included desquamation, scabbing, discoloration, tenderness, dryness, crusting, fissures, soreness, ulceration, swelling/edema, tingling, rash, and blisters.
- The most common systemic adverse event reported during the clinical studies was headache (7%).
## Postmarketing Experience
There is limited information regarding Podofilox Postmarketing Experience in the drug label.
# Drug Interactions
There is limited information regarding Podofilox Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C: 0.5% podofilox solution was not teratogenic in the rabbit following topical application of up to 0.21 mg/kg (2.85 mg/m2, approximately 2 times the maximum human dose) once daily for 13 days. The scientific literature contains references that podofilox is embryotoxic in rats when administered intraperitoneally at a dose of 5 mg/kg (29.5 mg/m2, approximately 19 times the recommended maximum human dose.)9 Teratogenicity and embryotoxicity have not been studied with intravaginal application. Many antimitotic drug products are known to be embryotoxic. There are no adequate and well-controlled studies in pregnant women. Condylox Gel 0.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Podofilox in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Podofilox during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from podofilox, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
There is no FDA guidance on the use of Podofilox in geriatric settings.
### Gender
There is no FDA guidance on the use of Podofilox with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Podofilox with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Podofilox in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Podofilox in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Podofilox in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Podofilox in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- The prescriber should ensure that the patient is fully aware of the correct method of therapy and identify which specific warts should be treated.
- Apply twice daily for 3 consecutive days, then discontinue for 4 consecutive days. This one week cycle of treatment may be repeated until there is no visible wart tissue or for a maximum of four cycles. If there is incomplete response after four treatment cycles, discontinue treatment and consider alternative treatment. Safety and effectiveness of more than four treatment cycles has not been established. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption.
- Condylox Gel 0.5% should be applied to the warts with the applicator tip or finger. Application on the surrounding normal tissue should be minimized. Treatment should be limited to 10 cm2 or less of wart tissue and to no more than 0.5 g of the gel per day.
- Care should be taken to allow the gel to dry before allowing the return of opposing skin surfaces to their normal positions. Patients should be instructed to wash their hands thoroughly before and after each application.
### Monitoring
There is limited information regarding Podofilox Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Podofilox and IV administrations.
# Overdosage
- Topically applied podofilox may be absorbed systemically. Toxicity reported following systemic administration of podofilox in investigational use for cancer treatment included: nausea, vomiting, fever, diarrhea, bone marrow depression, and oral ulcers. Following 5 to 10 daily intravenous doses of 0.5 to 1 mg/kg/day, significant hematological toxicity occurred but was reversible.10 Other toxicities occurred at lower doses. Toxicity reported following systemic administration of podophyllum resin included: nausea, vomiting, fever, diarrhea, peripheral neuropathy, altered mental status, lethargy, coma, tachypnea, respiratory failure, leukocytosis, pancytosis, hematuria, renal failure and seizures.11 Treatment of topical overdosage should include washing the skin free of any remaining drug and symptomatic and supportive therapy.
# Pharmacology
## Mechanism of Action
- Treatment of anogenital warts with podofilox results in necrosis of visible wart tissue. The exact mechanism of action is unknown.
## Structure
- Podofilox is an antimitotic drug which can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (e.g. species of Juniperus and Podophyllum). Condylox Gel 0.5% is formulated for topical administration. Each gram of gel contains 5 mg of podofilox in a buffered alcoholic gel containing alcohol, glycerin, lactic acid, hydroxypropyl cellulose, sodium lactate, and butylated hydroxytoluene.
- Podofilox has a molecular weight of 414.4 daltons, and is soluble in alcohol and sparingly soluble in water. Its chemical name is [5R,-(5α, 5aβ, 8aα, 9α]-5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl) furo[3',4':6,7]naphtho-[2,3,-d]-1,3-dioxol-6(5aH)-one.
- Podofilox has the following structural formula:
## Pharmacodynamics
There is limited information regarding Podofilox Pharmacodynamics in the drug label.
## Pharmacokinetics
- In systemic absorption studies in 52 patients, topical application of 0.05 mL of an ethanolic solution containing 0.5% podofilox to external genitalia did not result in detectable serum levels. Applications of 0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application. The elimination half-life ranged from 1.0 to 4.5 hours. The drug was not found to accumulate after multiple treatments1.
## Nonclinical Toxicology
Carcinogenesis, Mutagenesis and Impairment of Fertility
- An 80-week carcinogenicity study in the mouse was performed using a 0.5% podofilox solution applied dermally at 0.04, 0.2 and 1.0 mg/kg/day. There were no differences between the podofilox treated mice at any dose level and vehicle control in the incidence of neoplasia. Published animal studies, in general, have not shown the drug substance, podofilox, to be carcinogenic.2,3,4,5,6 There are published reports that, in mouse studies, crude podophyllin resin (containing podofilox) applied topically to the cervix produced changes resembling carcinoma in situ.7 These changes were reversible at five weeks after cessation of treatment. In one reported experiment, epidermal carcinoma of the vagina and cervix was found in 1 out of 18 mice after 120 applications of podophyllin8 (the drug was applied twice weekly over a 15-month period).
- Podofilox was not mutagenic in the Ames plate reverse mutation assay at concentrations up to 5 mg/plate, with and without metabolic activation. No cell transformation related to potential oncogenicity was observed in BALB/3T3 cells after exposure to podofilox at concentrations up to 0.008 μg/mL, without metabolic activation and 12 μg/mL podofilox with metabolic activation. Results from the mouse micronucleus in vivo assay using podofilox 0.5% solution at doses up to 25 mg/kg (75 mg/m2), indicate that podofilox should be considered a potential clastogen (a chemical that induces disruption and breakage of chromosomes).
- Daily topical application of 0.5% podofilox solution at doses up to the equivalent of 0.2 mg/kg (1.18 mg/m2, approximately equivalent to the human daily dose) to rats throughout gametogenesis, mating, gestation, parturition and lactation for two generations demonstrated no impairment of fertility.
# Clinical Studies
- In the first multicenter clinical study in 326 patients with anogenital warts, Condylox Gel 0.5% and its vehicle were applied in a double-blind fashion to comparable patient groups. Of the 260 patients with efficacy data, 176 were treated with Condylox Gel 0.5%. Patients applied Condylox Gel 0.5% twice daily for three consecutive days followed by a 4 day “rest” period.
- At the end of 4 weeks, 38.4% of the patients had complete clearing of the wart tissue when treated with Condylox Gel 0.5%.
- In the second multicenter clinical trial in 108 evaluable patients with anogenital warts, Condylox (podofilox) Topical Solution 0.5% was compared with Condylox Gel 0.5% for efficacy. As in the first clinical trial, patients applied Condylox Gel 0.5% twice daily for three consecutive days followed by a four day “rest” period.
- Similar clearance rates were observed. At the end of 4 weeks, 25.6% of the patients had complete clearing of the wart tissue when treated with Condylox Gel 0.5%.
# How Supplied
- Condylox Gel 0.5% is supplied as 3.5 g of clear gel in aluminum tubes with an applicator tip. NDC 52544-045-13. Store at 20-25°C (68-77°F). [See USP controlled room temperature.]
## Storage
- Avoid excessive heat. Do not freeze.
- Keep out of reach of children.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Information for Patients
- Patients using Condylox Gel 0.5% should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not intended to disclose all possible adverse or intended effects.
- This medication should be used only as directed by the health care provider. Patients should be instructed to wash their hands thoroughly before and after each application. It is for external use only. Avoid contact with the eyes.
- Patients should be advised not to use this medication for any disorder other than for which it was prescribed.
- Patients should report any signs of adverse reactions to the health care provider.
- If no improvement is observed after 4 weeks of treatment, discontinue the medication and consult the health care provider.
# Precautions with Alcohol
Alcohol-Podofilox interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Condylox
# Look-Alike Drug Names
There is limited information regarding Podofilox Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Podofilox | |
51fb0b295bd22b1950593e7c0b7a63a525c44478 | wikidoc | Polygraph | Polygraph
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A polygraph (from the Greek πολύς /po΄lis/ many and γράφειν /΄ɣrafin/ to write) (popularly referred to as a lie detector) is an instrument that measures and records several physiological responses such as blood pressure, pulse, respiration, breathing rhythms, body temperature and skin conductivity while the subject is asked and answers a series of questions, on the theory that false answers will produce distinctive measurements. The polygraph measures physiological changes caused by the sympathetic nervous system during questioning. Within the US federal government, a polygraph examination is also referred to as a psychophysiological detection of deception (PDD) examination.
Polygraphs are in some countries used as an interrogation tool with criminal suspects or candidates for sensitive public or private sector employment. The use and effectiveness of the polygraph is controversial, with the manner of its use and its validity subject to increasing criticism.
# History
The idea that lying produces physical side-effects has long been claimed. In West Africa persons suspected of a crime were made to pass a bird's egg to one another. If a person broke the egg, then he or she was considered guilty, based on the idea that their nervousness was to blame. In ancient China the suspect held a handful of rice in his or her mouth during a prosecutor's speech. Because salivation was believed to cease at times of emotional anxiety, the person was considered guilty if by the end of that speech the rice was dry.
Early devices for lie detection include an 1885 invention of Cesare Lombroso used to measure changes in blood pressure for police cases, a 1914 device by Vittorio Benussi used to measure breathing, and an abandoned project by American William Moulton Marston|William Marston which used blood pressure and galvanic skin response to examine German Prisoners Of War (POW).
A device recording both blood-pressure and galvanic skin response was invented in 1920 by Dr. John A. Larson of the University of California and first applied in law enforcement work by the Berkeley, California|Berkeley Police Department under its nationally renowned police chief August Vollmer. Further work on this device was done by Leonarde Keeler.
Makenzie wrote a second paper on the concept in 1915, when finishing his undergraduate studies. He entered Harvard Law School and graduated in 1918, re-publishing his earlier work in 1917. According to their son, Marston's wife, Elizabeth Holloway Marston, was also involved in the development of the systolic blood-pressure test: "According to Marston’s son, it was his mother Elizabeth, Marston’s wife, who suggested to him that 'When she got mad or excited, her blood pressure seemed to climb' (Lamb, 2001). Although Elizabeth is not listed as Marston’s collaborator in his early work, Lamb, Matte (1996), and others refer directly and indirectly to Elizabeth’s work on her husband’s deception research. She also appears in a picture taken in his polygraph laboratory in the 1920s (reproduced in Marston, 1938)." The comic book character, Wonder Woman by William Marston (and influenced by Elizabeth Marston ) carries a Lasso of Truth|magic lasso which was modelled upon the pneumograph (breathing monitor) test.
Marston was the self proclaimed “father of the polygraph” despite his predecessor's contributions.
Marston remained the device's primary advocate, lobbying for its use in the courts. In 1938 he published a book, The Lie Detector Test, wherein he documented the theory and use of the device. In 1938 he appeared in advertising by the Gillette company claiming that the polygraph showed Gillette razors were better than the competition.
# Testing procedure
Today, polygraph examiners use two types of instrumentation: analog and computerized. In the United States, most examiners now use computerized instrumentation.
A typical polygraph test starts with a pre-test interview to gain some preliminary information which will later be used for "Control Questions", or CQ. Then the tester will explain how the polygraph is supposed to work, emphasizing that it can detect lies and that it is important to answer truthfully. Then a "stim test" is often conducted: the subject is asked to deliberately lie and then the tester reports that he was able to detect this lie. Then the actual test starts. Some of the questions asked are "Irrelevant " or IR ("Is your name Lebron James?"), others are "probable-lie" Control Questions that most people will lie about ("Have you ever stolen money?") and the remainder are the "Relevant Questions ", or RQ, that the tester is really interested in. The different types of questions alternate. The test is passed if the physiological responses during the probable-lie control questions (CQ) are larger than those during the relevant questions (RQ). If this is not the case, the tester attempts to elicit admissions during a post-test interview, for example, "Your situation will only get worse if we don't clear this up".
Criticisms have been given regarding the validity of the administration of the Control Questions test (CQT). The CQT may be vulnerable to be conducted in an interrogation-like fashion. This kind of interrogation style would elicit a nervous response from innocent and guilty suspects alike. There are several other ways of administrating the questions.
An alternative is the Guilty Knowledge test (GKT), or the Concealed Information Test (CIT). The administration of this test is given to prevent potential errors that may arise from the questioning style. The test is usually conducted by a tester with no knowledge of the crime or circumstances in question. The administrator tests the participant on their knowledge of the crime that would not be known to an innocent person. For example: “Was the crime committed with a .45 or a 9 mm?” The questions are in multiple choice and the participant is rated on how they react to the correct answer. If they react strongly to the guilty information, then proponents of the test believe that it is likely that they know facts relevant to the case. This administration is considered more valid by supporters of the test because it contains many safeguards to avoid the risk of the administrator influencing the results.
# Reliability
There is little scientific evidence to support the reliability of polygraphs. Despite claims of 90% - 95% reliability, critics charge that rather than a "test", the method amounts to an inherently unstandardizable interrogation technique whose accuracy cannot be established. A 1997 survey of 421 psychologists estimated the test's average accuracy at about 61%, a little better than chance. Critics also argue that even given high estimates of the polygraph's accuracy a significant number of subjects (e.g. 10% given a 90% accuracy) will appear to be lying, and would unfairly suffer the consequences of "failing" the polygraph. In the 1998 Supreme Court of the United States|Supreme Court case, United States v. Scheffer, the majority stated that "There is simply no consensus that polygraph evidence is reliable" and "Unlike other expert witnesses who testify about factual matters outside the jurors' knowledge, such as the analysis of fingerprints, ballistics, or DNA found at a crime scene, a polygraph expert can supply the jury only with another opinion..." Also, in 2005 the 11th Circuit Court of Appeals stated that “polygraphy did not enjoy general acceptance from the scientific community”. Charles Honts, a psychology professor at Boise State University, states that polygraph interrogations give a high rate of false positives on innocent people. In 2001 William G. Iacono, Distinguished McKnight University Professor of Psychology and Neuroscience and Director, Clinical Science and Psychopathology Research Training Program at the University of Minnesota, published a paper titled “Forensic “Lie Detection": Procedures Without Scientific Basis” in the peer reviewed Journal of Forensic Psychology Practice. He concluded that
Although the CQT may be useful as an investigative aid and tool to induce confessions, it does not pass muster as a scientifically credible test. CQT theory is based on naive, implausible assumptions indicating (a) that it is biased against innocent individuals and (b) that it can be beaten simply by artificially augmenting responses to control questions. Although it is not possible to adequately assess the error rate of the CQT, both of these conclusions are supported by published research findings in the best social science journals (Honts et al., 1994; Horvath, 1977; Kleinmuntz & Szucko, 1984; Patrick & Iacono, 1991). Although defense attorneys often attempt to have the results of friendly CQTs admitted as evidence in court, there is no evidence supporting their validity and ample reason to doubt it. Members of scientific organizations who have the requisite background to evaluate the CQT are overwhelmingly skeptical of the claims made by polygraph proponents.
Polygraph tests have also been criticized for failing to trap known spying|spies such as double-agent Aldrich Ames, who passed two polygraph tests while spying for the Soviet Union. Other spies who passed the polygraph include Karl Koecher, Ana Montes|Ana Belen Montes, and Leandro Aragoncillo. Pseudoscience debunker Robert L. Park|Bob Park said, "The polygraph, in fact, has ruined careers, but never uncovered a single spy." Polygraph examination and background checks also failed to detect Nada Nadim Prouty, who was not a spy but was convicted for improperly obtaining US citizenship and using it to obtain a restricted position at the FBI.
Prolonged polygraph examinations are sometimes used as a tool by which confession (legal)|confessions are extracted from a defendant, as in the case of Richard Miller (agent)|Richard Miller, who was persuaded to confess largely by polygraph results combined with appeals from a religious leader.
# Countermeasures
Several countermeasures designed to pass polygraph tests have been described. Asked how he passed the polygraph test, Ames explained that he sought advice from his Soviet handler and received the simple instruction to: "Get a good night's sleep, and rest, and go into the test rested and relaxed. Be nice to the polygraph examiner, develop a rapport, and be cooperative and try to maintain your calm."
Other suggested countermeasures include for the subject to mentally record the control and relevant questions as the examiner reviews them prior to commencing the interrogation. Once the interrogation begins, the subject is then supposed to carefully control their breathing during the relevant questions, and to try to artificially increase their heart rate during the control questions, such as by thinking of something scary or exciting or by pricking themselves with a pointed object concealed somewhere on their body. In this way the results will not show a significant reaction to any of the relevant questions.
# 2003 National Academy of Sciences report
The accuracy of the polygraph has been contested almost since the introduction of the device. In 2003, the National Academy of Sciences (NAS) issued a report entitled “The Polygraph and Lie Detection”. The NAS found that the majority of polygraph research was " Unreliable, Unscientific and Biased" (quote). The NAS study identified 57 of the 80 odd research studies that the APA relies on, to come to their conclusions. These studies concluded that a polygraph test regarding a specific incident can discern the truth at “a level slightly greater than chance, yet short of perfection”. The report also concluded that this level of accuracy was overstated and the levels of accuracy shown in these studies "are almost certainly higher than actual polygraph accuracy of specific-incident testing in the field.”
When polygraphs are used as a screening tool (in national security matters and for law enforcement agencies for example) the level of accuracy drops to such a level that “Its accuracy in distinguishing actual or potential security violators from innocent test takers is insufficient to justify reliance on its use in employee security screening in federal agencies.” In fact, the NAS extrapolated that if the test were sensitive enough to detect 80% of spies (a level of accuracy which it did not assume), this would hardly be sufficient anyway. Let us take for example a hypothetical polygraph screening of a body of 10,000 employees among which are 10 spies. With an 80% success rate, the polygraph test would show that 8 spies and 1,998 non-spies fail the test. Thus, roughly 99.6 percent of positives (those failing the test) would be false positives. The NAS concluded that the polygraph "...may have some utility" but that there is "little basis for the expectation that a polygraph test could have extremely high accuracy."
The NAS conclusions paralleled those of the earlier United States Congress Office of Technology Assessment report "Scientific Validity of Polygraph Testing: A Research Review and Evaluation”.
# Admissibility of polygraphs in court
## United States
In 2007, polygraph testimony was admitted by stipulation in 19 states, and was subject to the discretion of the trial judge in federal court. The use of polygraph in court testimony remains controversial, although it is used extensively in post-conviction supervision, particularly of sex offenders. In Daubert v. Merrell Dow Pharmaceuticals (1993), the old Frye standard was lifted and all forensic evidence, including polygraph, had to meet the new Daubert standard in which "underlying reasoning or methodology is scientifically valid and properly can be applied to the facts at issue." While polygraph tests are commonly used in police investigations in the US, no defendant or witness can be forced to undergo the test. In United States v. Scheffer (1998), the Supreme Court of the United States|U.S. Supreme Court left it up to individual jurisdictions whether polygraph results could be admitted as evidence in court cases. Nevertheless, it is used extensively by prosecutors, defense attorneys, and Policing in the United States|law enforcement agencies. In the States of Massachusetts, Maryland, New Jersey, Delaware and Iowa it is illegal for any employer to order a polygraph either as conditions to gain employment, or if an employee has been suspected of wrongdoing. The Employee Polygraph Protection Act of 1988 (EPPA) generally prevents employers from using lie detector tests, either for pre-employment screening or during the course of employment, with certain exemptions.
In the United States, the State of New Mexico admits polygraph testing in front of Jury|juries under certain circumstances. In many other states, polygraph examiners are permitted to testify in front of judges in various types of Hearing (law)|hearings (Motion (legal)|Motion to Revoke Probation, Motion to Adjudicate Guilt).
In 2007, in Ohio v. Sharma, an Ohio trial court overruled the objections of a prosecutor and allowed a polygraph examiner to testify regarding a specific issue criminal examination. The court took the position that the prosecutors regularly used a polygraph examiner to conduct criminal tests against defendants, but only objected to the examiner's testimony when the results contradicted what they hoped to achieve. Dr. Louis Rovner, a polygraph expert from California, tested the defendant and testified as an expert witness both at a pretrial admissibility hearing and at trial. The defendant, who had been charged with sexual battery, was acquitted.
## Europe
In most Europe]]an jurisdictions, polygraphs are not considered reliable evidence and are not generally used by police forces. However, in any lawsuit, an involved party can order a psychologist to write an opinion based on polygraph results to substantiate the credibility of its claims. The party must bear the expense themselves, and the court weighs the opinion like any other opinion the party has ordered. Courts themselves do not order or pay for polygraph tests. In most cases, polygraph tests are voluntarily taken by a defendant in order to substantiate his or her claims.
## Canada
In Canada, the polygraph is regularly used as a forensic tool in the investigation of criminal acts and sometimes employed in the screening of employees for government organizations. In the 1987 decision of R. v. Béland, the Supreme Court of Canada rejected the use of polygraph results as evidence in court. This decision did not however affect the use of the polygraph in criminal investigations. The polygraph continues to be used as an investigative tool.
## Australia
The High Court of Australia has not yet considered the admissibility of polygraph evidence. However, the New South Wales District Court rejected the use of the device in a criminal trial. In Raymond George Murray 1982 7A Crim R48 Sinclair DCJ refused to admit polygraph evidence tending to support the defence. His Honour rejected the evidence because
- The veracity of the accused and the weight to be given to his evidence, and other witnesses called in the trial, was a matter for the jury.
- The polygraph "expert" sought to express an opinion as to ultimate facts in issue, which is peculiarly the province of the jury.
- The test purported to be expert evidence by the witness who was not qualified as an expert, he was merely an operator and assessor of a polygraph. The scientific premise upon which his assessment was based had not been proved in any Court in Australia.
- Devoid of any proved or accepted scientific basis, the evidence of the operator is hearsay which is inadmissible.
The Court cited, with approval, the Canadian case of Phillion v R 1978 1SCR 18.
## Israel
The High Court of Israel, in Civil Appeal 551/89 (Menora Insurance Vs. Jacob Sdovnik), ruled that as the polygraph has not been recognized as a reliable device, polygraph results are inadmissible as evidence in a civil trial. In other decisions, polygraph results were ruled inadmissible in criminal trials. However, some insurance companies attempt to include a clause in insurance contracts, in which the beneficiary agrees that polygraph results be admissible as evidence. In such cases, where the beneficiary has willingly agreed to such a clause, signed the contract, and took the test, the courts will honor the contract, and take the polygraph results into consideration. Interestingly, it is common practice for lawyers to advise people who signed such contracts to refuse to take the test. Depending on whether or not the beneficiary signed an agreements clause, and whether the test was already taken or not, such a refusal usually has no ill effects; At worst, the court will simply order the person to take the test as agreed. At best, the court will cancel the clause and release the person from taking the test, or rule the evidence inadmissible.
## India
Recently an Indian court adopted the brain electrical oscillations signature test as evidence to convict a woman, who was accused of murdering her fiance. It is the first time that the result of polygraph was used as evidence in court.
# Use with espionage and security clearances
In the American military and intelligence communities, polygraphs have been administered both as terms of qualifying for a security clearance and as part of a periodic reinvestigation to retain a clearance. There is no uniform standard for whether the polygraph is needed, as some methods of adjudication do not demand a successful polygraph test to earn a clearance. Other agencies, particularly certain military units, actually prohibit polygraph testing on their members.
It is difficult to precisely determine the effectiveness of polygraph results for the detection or deterrence of spying. Failure of a polygraph test could cause revocation of a security clearance, but it is inadmissible evidence in most federal courts and military courts martial. The polygraph is more often used as a deterrent to espionage rather than detection. One exception to this was the case of Harold James Nicholson, a CIA employee later convicted of spying for Russia. In 1995, Nicholson had undergone his periodic five year reinvestigation where he showed a strong probability of deception on questions regarding relationships with a foreign intelligence unit. This polygraph test later launched an investigation which resulted in his eventual arrest and conviction. In most cases, however, polygraphs are more of a tool to "scare straight" those who would consider espionage. Jonathan Pollard was advised by his Israeli handlers that he was to resign his job from American intelligence if he was ever told he was subject to a polygraph test. Likewise, John Anthony Walker was advised to by his handlers not to engage in espionage until he had been promoted to the highest position for which a polygraph test was not required, to refuse promotion to higher positions for which polygraph tests were required, and to retire when promotion was mandated. As part of his plea bargain agreement for his case of espionage against the Soviet Union, Robert Hanssen would be made to undergo a polygraph at any time as part of damage assessment. In Hanssen's 25-year career with the FBI, not once was he made to undergo a polygraph. He later said if he had been ordered; he may have thought twice about espionage.
Alternatively, the use of polygraph testing, where it causes desperation over dismissal for past dishonesty, may encourage spying. For example, Edward Lee Howard was dismissed from the CIA after during a polygraph screen, he truthfully answered a series of questions admitting to minor crimes such as petty theft and drug abuse. The CIA failed to see that the firing was an action that would logically anger Howard, and in retaliation for his perceived unjust punishment for minor offenses, he later sold his knowledge of CIA operations to the Soviet Union.
It is also worth noting that polygraph tests may not deter espionage. From 1945 to the present, at least six Americans had been committing espionage while they successfully passed polygraph tests. Two of the most notable cases of two men who created a false negative result with the polygraphs were Larry Wu-Tai Chin and Aldrich Ames.
In August 2008, the US Defense Intelligence Agency announced that it would subject each of its 5,700 prospective and current employees to a polygraph interrogation at least once annually.
# Hand-held lie detector for U.S. military
A hand-held lie detector is being deployed by the U.S. Defense Department, according to a report in 2008 by investigative reporter Bill Dedman of msnbc.com. The Preliminary Credibility Assessment Screening System, or PCASS, captures less physiological information than a polygraph, and uses an algorithm, not the judgement of a polygraph examiner, to render a decision whether it believes the person is being deceptive or not. The device will be used first in Afghanistan by U.S. Army troops. The law states that it could only legally be used on non-U.S. persons.
# Use with sex offenders
Sexual offenders are now routinely polygraphed in many states of the United States and it is often a mandatory condition of probation or parole. In Texas, a state appellate court has upheld the testing of sex offenders under community supervision and has also upheld written statements given by sex offenders if they have committed a further offense with new victims. These statements are then used when a motion is filed to revoke probation and the probationer may then be sentenced to prison for having violated his or her probation.
A significant number of Federal appeals courts have upheld polygraph testing for Federal probationers as well. The most recent decision was by the Second Circuit Court of Appeals regarding a New York sex offender.
The UK will soon allow compulsory polygraph tests for convicted sex offenders released on license.
# Polygraph in popular culture
Lie detection has a long history in mythology and fairy tales; the polygraph has allowed modern fiction to use a device more easily seen as scientific and plausible. Notable instances of polygraph usage include uses in crime and espionage themed television shows and some daytime television talk shows, cartoons and films. The most notable polygraph TV show is Lie Detector (TV series)|Lie Detector, which first aired in the 1950s created and hosted by Ralph Andrews. Then in the 1960s Ralph produced a series of specials hosted by Melvin Belli, then in the 1970s hosted by Jack Anderson. In 1998 TV producer Mark Phillips with his Mark Phillips Philms & Telephision put Lie Detector back on the air on the FOX Network -- on that program Dr. Ed Gelb with host Marcia Clark cleared Mark Fuhrman from the allegation that he "planted the bloody glove." Later Phillips produced Lie Detector as a series for PAX/ION -- some of the guests included Paula Jones, Reverend Paul Crouch accuser Lonny Ford, Ben Rowling, Jeff Gannon and Swift Boat Vet Steve Garner.
FOX has taken this one step further with their game show The Moment of Truth (US game show)|The Moment of Truth which pits people's honesty against their own sense of modesty, propriety, etc. Contestants are given a polygraph test administered by a polygraph expert in a pre-screening session answering over 50 questions. Later they must sit in front of a studio audience including their friends & family for the televised portion of the show. There they need only answer 21 answers truthfully "as determined by the polygraph" to win $500,000. The questions get more personal and/or more revealing as they advance. Most polygraph experts caution that the polygraph techniques used on Moment of Truth do not conform to any known or accepted methods of polygraphy.
Daytime talk shows, such as Maury Povich, frequently uses lie detectors in order to tell if someone is cheating on their significant other.
In the movie Ocean's 13, one of the characters beats a polygraph test by stepping on a tack when answering truthfully, which supposedly raises the polygraph's readings for the truthful answers so they equal to the deceptive ones.
In episode 109 of the USA popular science show Mythbusters, they attempted to fool the polygraph by using pain to try to increase the readings when answering truthfully (so the machine will supposedly interpret the truthful and non-truthful answers as the same.) They also attempted to fool the polygraph by thinking happy thoughts when lying and thinking stressful thoughts when telling the truth to try to confuse the machine. However, neither technique was successful for a number of reasons. Michael Martin correctly identified each guilty and innocent subject. The show also noted the widely held opinion that, when done properly, polygraphs are correct 80-99% of the time. | Polygraph
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Template:Otheruses4
A polygraph (from the Greek πολύς /po΄lis/ many and γράφειν /΄ɣrafin/ to write) (popularly referred to as a lie detector) is an instrument that measures and records several physiological responses such as blood pressure, pulse, respiration, breathing rhythms, body temperature and skin conductivity while the subject is asked and answers a series of questions, on the theory that false answers will produce distinctive measurements. The polygraph measures physiological changes caused by the sympathetic nervous system during questioning. Within the US federal government, a polygraph examination is also referred to as a psychophysiological detection of deception (PDD) examination.
Polygraphs are in some countries used as an interrogation tool with criminal suspects or candidates for sensitive public or private sector employment. The use and effectiveness of the polygraph is controversial, with the manner of its use and its validity subject to increasing criticism.
# History
The idea that lying produces physical side-effects has long been claimed. In West Africa persons suspected of a crime were made to pass a bird's egg to one another.[citation needed] If a person broke the egg, then he or she was considered guilty, based on the idea that their nervousness was to blame. In ancient China the suspect held a handful of rice in his or her mouth during a prosecutor's speech.[citation needed] Because salivation was believed to cease at times of emotional anxiety, the person was considered guilty if by the end of that speech the rice was dry.
Early devices for lie detection include an 1885 invention of Cesare Lombroso used to measure changes in blood pressure for police cases, a 1914 device by Vittorio Benussi used to measure breathing, and an abandoned project by American William Moulton Marston|William Marston which used blood pressure and galvanic skin response to examine German Prisoners Of War (POW).[1]
A device recording both blood-pressure and galvanic skin response was invented in 1920 by Dr. John A. Larson of the University of California and first applied in law enforcement work by the Berkeley, California|Berkeley Police Department under its nationally renowned police chief August Vollmer. Further work on this device was done by Leonarde Keeler.[2]
Makenzie wrote a second paper on the concept in 1915, when finishing his undergraduate studies. He entered Harvard Law School and graduated in 1918, re-publishing his earlier work in 1917.[3] According to their son, Marston's wife, Elizabeth Holloway Marston, was also involved in the development of the systolic blood-pressure test: "According to Marston’s son, it was his mother Elizabeth, Marston’s wife, who suggested to him that 'When she got mad or excited, her blood pressure seemed to climb' (Lamb, 2001). Although Elizabeth is not listed as Marston’s collaborator in his early work, Lamb, Matte (1996), and others refer directly and indirectly to Elizabeth’s work on her husband’s deception research. She also appears in a picture taken in his polygraph laboratory in the 1920s (reproduced in Marston, 1938)."[4][5] The comic book character, Wonder Woman by William Marston (and influenced by Elizabeth Marston[6][7] ) carries a Lasso of Truth|magic lasso which was modelled upon the pneumograph (breathing monitor) test.[8][6]
Marston was the self proclaimed “father of the polygraph” despite his predecessor's contributions.
Marston remained the device's primary advocate, lobbying for its use in the courts. In 1938 he published a book, The Lie Detector Test, wherein he documented the theory and use of the device.[9] In 1938 he appeared in advertising by the Gillette company claiming that the polygraph showed Gillette razors were better than the competition.[10][11][12]
# Testing procedure
Template:Globalise
Today, polygraph examiners use two types of instrumentation: analog and computerized. In the United States, most examiners now use computerized instrumentation.
A typical polygraph test starts with a pre-test interview to gain some preliminary information which will later be used for "Control Questions", or CQ. Then the tester will explain how the polygraph is supposed to work, emphasizing that it can detect lies and that it is important to answer truthfully. Then a "stim test" is often conducted: the subject is asked to deliberately lie and then the tester reports that he was able to detect this lie. Then the actual test starts. Some of the questions asked are "Irrelevant " or IR ("Is your name Lebron James?"), others are "probable-lie" Control Questions that most people will lie about ("Have you ever stolen money?") and the remainder are the "Relevant Questions ", or RQ, that the tester is really interested in. The different types of questions alternate. The test is passed if the physiological responses during the probable-lie control questions (CQ) are larger than those during the relevant questions (RQ). If this is not the case, the tester attempts to elicit admissions during a post-test interview, for example, "Your situation will only get worse if we don't clear this up".[13][14]
Criticisms have been given regarding the validity of the administration of the Control Questions test (CQT). The CQT may be vulnerable to be conducted in an interrogation-like fashion. This kind of interrogation style would elicit a nervous response from innocent and guilty suspects alike. There are several other ways of administrating the questions.
An alternative is the Guilty Knowledge test (GKT), or the Concealed Information Test (CIT). The administration of this test is given to prevent potential errors that may arise from the questioning style. The test is usually conducted by a tester with no knowledge of the crime or circumstances in question. The administrator tests the participant on their knowledge of the crime that would not be known to an innocent person. For example: “Was the crime committed with a .45 or a 9 mm?” The questions are in multiple choice and the participant is rated on how they react to the correct answer. If they react strongly to the guilty information, then proponents of the test believe that it is likely that they know facts relevant to the case. This administration is considered more valid by supporters of the test because it contains many safeguards to avoid the risk of the administrator influencing the results. [15]
# Reliability
There is little scientific evidence to support the reliability of polygraphs.[16][17] Despite claims of 90% - 95% reliability, critics charge that rather than a "test", the method amounts to an inherently unstandardizable interrogation technique whose accuracy cannot be established. A 1997 survey of 421 psychologists estimated the test's average accuracy at about 61%, a little better than chance.[18] Critics also argue that even given high estimates of the polygraph's accuracy a significant number of subjects (e.g. 10% given a 90% accuracy) will appear to be lying, and would unfairly suffer the consequences of "failing" the polygraph. In the 1998 Supreme Court of the United States|Supreme Court case, United States v. Scheffer, the majority stated that "There is simply no consensus that polygraph evidence is reliable" and "Unlike other expert witnesses who testify about factual matters outside the jurors' knowledge, such as the analysis of fingerprints, ballistics, or DNA found at a crime scene, a polygraph expert can supply the jury only with another opinion..."[19] Also, in 2005 the 11th Circuit Court of Appeals stated that “polygraphy did not enjoy general acceptance from the scientific community”.[20] Charles Honts, a psychology professor at Boise State University, states that polygraph interrogations give a high rate of false positives on innocent people.[21] In 2001 William G. Iacono, Distinguished McKnight University Professor of Psychology and Neuroscience and Director, Clinical Science and Psychopathology Research Training Program at the University of Minnesota, published a paper titled “Forensic “Lie Detection": Procedures Without Scientific Basis” in the peer reviewed Journal of Forensic Psychology Practice. He concluded that
Although the CQT [Control Question Test] may be useful as an investigative aid and tool to induce confessions, it does not pass muster as a scientifically credible test. CQT theory is based on naive, implausible assumptions indicating (a) that it is biased against innocent individuals and (b) that it can be beaten simply by artificially augmenting responses to control questions. Although it is not possible to adequately assess the error rate of the CQT, both of these conclusions are supported by published research findings in the best social science journals (Honts et al., 1994; Horvath, 1977; Kleinmuntz & Szucko, 1984; Patrick & Iacono, 1991). Although defense attorneys often attempt to have the results of friendly CQTs admitted as evidence in court, there is no evidence supporting their validity and ample reason to doubt it. Members of scientific organizations who have the requisite background to evaluate the CQT are overwhelmingly skeptical of the claims made by polygraph proponents.
[22]
Polygraph tests have also been criticized for failing to trap known spying|spies such as double-agent Aldrich Ames, who passed two polygraph tests while spying for the Soviet Union.[21][23] Other spies who passed the polygraph include Karl Koecher,[24] Ana Montes|Ana Belen Montes,[25] and Leandro Aragoncillo.[26] Pseudoscience debunker Robert L. Park|Bob Park said, "The polygraph, in fact, has ruined careers, but never uncovered a single spy."[27] Polygraph examination and background checks also failed to detect Nada Nadim Prouty, who was not a spy but was convicted for improperly obtaining US citizenship and using it to obtain a restricted position at the FBI.[28]
Prolonged polygraph examinations are sometimes used as a tool by which confession (legal)|confessions are extracted from a defendant, as in the case of Richard Miller (agent)|Richard Miller, who was persuaded to confess largely by polygraph results combined with appeals from a religious leader.[29]
# Countermeasures
Several countermeasures designed to pass polygraph tests have been described. Asked how he passed the polygraph test, Ames explained that he sought advice from his Soviet handler and received the simple instruction to: "Get a good night's sleep, and rest, and go into the test rested and relaxed. Be nice to the polygraph examiner, develop a rapport, and be cooperative and try to maintain your calm."[30]
Other suggested countermeasures include for the subject to mentally record the control and relevant questions as the examiner reviews them prior to commencing the interrogation. Once the interrogation begins, the subject is then supposed to carefully control their breathing during the relevant questions, and to try to artificially increase their heart rate during the control questions, such as by thinking of something scary or exciting or by pricking themselves with a pointed object concealed somewhere on their body. In this way the results will not show a significant reaction to any of the relevant questions.[31][32]
# 2003 National Academy of Sciences report
The accuracy of the polygraph has been contested almost since the introduction of the device. In 2003, the National Academy of Sciences (NAS) issued a report entitled “The Polygraph and Lie Detection”. The NAS found that the majority of polygraph research was " Unreliable, Unscientific and Biased" (quote). The NAS study identified 57 of the 80 odd research studies that the APA relies on, to come to their conclusions. These studies concluded that a polygraph test regarding a specific incident can discern the truth at “a level slightly greater than chance, yet short of perfection”. The report also concluded that this level of accuracy was overstated and the levels of accuracy shown in these studies "are almost certainly higher than actual polygraph accuracy of specific-incident testing in the field.”[33]
When polygraphs are used as a screening tool (in national security matters and for law enforcement agencies for example) the level of accuracy drops to such a level that “Its accuracy in distinguishing actual or potential security violators from innocent test takers is insufficient to justify reliance on its use in employee security screening in federal agencies.” In fact, the NAS extrapolated that if the test were sensitive enough to detect 80% of spies (a level of accuracy which it did not assume), this would hardly be sufficient anyway. Let us take for example a hypothetical polygraph screening of a body of 10,000 employees among which are 10 spies. With an 80% success rate, the polygraph test would show that 8 spies and 1,998 non-spies fail the test. Thus, roughly 99.6 percent of positives (those failing the test) would be false positives. The NAS concluded that the polygraph "...may have some utility"[33] but that there is "little basis for the expectation that a polygraph test could have extremely high accuracy."[34]
The NAS conclusions paralleled those of the earlier United States Congress Office of Technology Assessment report "Scientific Validity of Polygraph Testing: A Research Review and Evaluation”.[35]
# Admissibility of polygraphs in court
## United States
In 2007, polygraph testimony was admitted by stipulation in 19 states, and was subject to the discretion of the trial judge in federal court. The use of polygraph in court testimony remains controversial, although it is used extensively in post-conviction supervision, particularly of sex offenders. In Daubert v. Merrell Dow Pharmaceuticals (1993),[36] the old Frye standard was lifted and all forensic evidence, including polygraph, had to meet the new Daubert standard in which "underlying reasoning or methodology is scientifically valid and properly can be applied to the facts at issue." While polygraph tests are commonly used in police investigations in the US, no defendant or witness can be forced to undergo the test. In United States v. Scheffer (1998),[37] the Supreme Court of the United States|U.S. Supreme Court left it up to individual jurisdictions whether polygraph results could be admitted as evidence in court cases. Nevertheless, it is used extensively by prosecutors, defense attorneys, and Policing in the United States|law enforcement agencies. In the States of Massachusetts, Maryland, New Jersey, Delaware and Iowa it is illegal for any employer to order a polygraph either as conditions to gain employment, or if an employee has been suspected of wrongdoing. The Employee Polygraph Protection Act of 1988 (EPPA) generally prevents employers from using lie detector tests, either for pre-employment screening or during the course of employment, with certain exemptions.[38]
In the United States, the State of New Mexico admits polygraph testing in front of Jury|juries under certain circumstances. In many other states, polygraph examiners are permitted to testify in front of judges in various types of Hearing (law)|hearings (Motion (legal)|Motion to Revoke Probation, Motion to Adjudicate Guilt).
In 2007, in Ohio v. Sharma, an Ohio trial court overruled the objections of a prosecutor and allowed a polygraph examiner to testify regarding a specific issue criminal examination. The court took the position that the prosecutors regularly used a polygraph examiner to conduct criminal tests against defendants, but only objected to the examiner's testimony when the results contradicted what they hoped to achieve.[39] Dr. Louis Rovner[8], a polygraph expert from California, tested the defendant and testified as an expert witness both at a pretrial admissibility hearing and at trial. The defendant, who had been charged with sexual battery, was acquitted.[40]
## Europe
In most Europe]]an jurisdictions, polygraphs are not considered reliable evidence and are not generally used by police forces. However, in any lawsuit, an involved party can order a psychologist to write an opinion based on polygraph results to substantiate the credibility of its claims. The party must bear the expense themselves, and the court weighs the opinion like any other opinion the party has ordered. Courts themselves do not order or pay for polygraph tests. In most cases, polygraph tests are voluntarily taken by a defendant in order to substantiate his or her claims.
## Canada
In Canada, the polygraph is regularly used as a forensic tool in the investigation of criminal acts and sometimes employed in the screening of employees for government organizations. In the 1987 decision of R. v. Béland, the Supreme Court of Canada rejected the use of polygraph results as evidence in court. This decision did not however affect the use of the polygraph in criminal investigations. The polygraph continues to be used as an investigative tool.
## Australia
The High Court of Australia has not yet considered the admissibility of polygraph evidence. However, the New South Wales District Court rejected the use of the device in a criminal trial. In Raymond George Murray 1982 7A Crim R48 Sinclair DCJ refused to admit polygraph evidence tending to support the defence. His Honour rejected the evidence because
- The veracity of the accused and the weight to be given to his evidence, and other witnesses called in the trial, was a matter for the jury.
- The polygraph "expert" sought to express an opinion as to ultimate facts in issue, which is peculiarly the province of the jury.
- The test purported to be expert evidence by the witness who was not qualified as an expert, he was merely an operator and assessor of a polygraph. The scientific premise upon which his assessment was based had not been proved in any Court in Australia.
- Devoid of any proved or accepted scientific basis, the evidence of the operator is hearsay which is inadmissible.
The Court cited, with approval, the Canadian case of Phillion v R 1978 1SCR 18.
## Israel
The High Court of Israel, in Civil Appeal 551/89 (Menora Insurance Vs. Jacob Sdovnik), ruled that as the polygraph has not been recognized as a reliable device, polygraph results are inadmissible as evidence in a civil trial. In other decisions, polygraph results were ruled inadmissible in criminal trials. However, some insurance companies attempt to include a clause in insurance contracts, in which the beneficiary agrees that polygraph results be admissible as evidence. In such cases, where the beneficiary has willingly agreed to such a clause, signed the contract, and took the test, the courts will honor the contract, and take the polygraph results into consideration. Interestingly, it is common practice for lawyers to advise people who signed such contracts to refuse to take the test. Depending on whether or not the beneficiary signed an agreements clause, and whether the test was already taken or not, such a refusal usually has no ill effects; At worst, the court will simply order the person to take the test as agreed. At best, the court will cancel the clause and release the person from taking the test, or rule the evidence inadmissible.
## India
Recently an Indian court adopted the brain electrical oscillations signature test as evidence to convict a woman, who was accused of murdering her fiance. It is the first time that the result of polygraph was used as evidence in court.[41]
# Use with espionage and security clearances
Template:Globalise
In the American military and intelligence communities, polygraphs have been administered both as terms of qualifying for a security clearance and as part of a periodic reinvestigation to retain a clearance. There is no uniform standard for whether the polygraph is needed, as some methods of adjudication do not demand a successful polygraph test to earn a clearance. Other agencies, particularly certain military units, actually prohibit polygraph testing on their members.
It is difficult to precisely determine the effectiveness of polygraph results for the detection or deterrence of spying. Failure of a polygraph test could cause revocation of a security clearance, but it is inadmissible evidence in most federal courts and military courts martial. The polygraph is more often used as a deterrent to espionage rather than detection. One exception to this was the case of Harold James Nicholson, a CIA employee later convicted of spying for Russia. In 1995, Nicholson had undergone his periodic five year reinvestigation where he showed a strong probability of deception on questions regarding relationships with a foreign intelligence unit. This polygraph test later launched an investigation which resulted in his eventual arrest and conviction. In most cases, however, polygraphs are more of a tool to "scare straight" those who would consider espionage. Jonathan Pollard was advised by his Israeli handlers that he was to resign his job from American intelligence if he was ever told he was subject to a polygraph test. Likewise, John Anthony Walker was advised to by his handlers not to engage in espionage until he had been promoted to the highest position for which a polygraph test was not required, to refuse promotion to higher positions for which polygraph tests were required, and to retire when promotion was mandated.[42] As part of his plea bargain agreement for his case of espionage against the Soviet Union, Robert Hanssen would be made to undergo a polygraph at any time as part of damage assessment. In Hanssen's 25-year career with the FBI, not once was he made to undergo a polygraph. He later said if he had been ordered; he may have thought twice about espionage.
Alternatively, the use of polygraph testing, where it causes desperation over dismissal for past dishonesty, may encourage spying. For example, Edward Lee Howard was dismissed from the CIA after during a polygraph screen, he truthfully answered a series of questions admitting to minor crimes such as petty theft and drug abuse. The CIA failed to see that the firing was an action that would logically anger Howard, and in retaliation for his perceived unjust punishment for minor offenses, he later sold his knowledge of CIA operations to the Soviet Union.[43]
It is also worth noting that polygraph tests may not deter espionage. From 1945 to the present, at least six Americans had been committing espionage while they successfully passed polygraph tests. Two of the most notable cases of two men who created a false negative result with the polygraphs were Larry Wu-Tai Chin and Aldrich Ames.
In August 2008, the US Defense Intelligence Agency announced that it would subject each of its 5,700 prospective and current employees to a polygraph interrogation at least once annually.[21]
# Hand-held lie detector for U.S. military
A hand-held lie detector is being deployed by the U.S. Defense Department, according to a report in 2008 by investigative reporter Bill Dedman of msnbc.com. The Preliminary Credibility Assessment Screening System, or PCASS, captures less physiological information than a polygraph, and uses an algorithm, not the judgement of a polygraph examiner, to render a decision whether it believes the person is being deceptive or not. The device will be used first in Afghanistan by U.S. Army troops. The law states that it could only legally be used on non-U.S. persons. [44]
# Use with sex offenders
Sexual offenders are now routinely polygraphed in many states of the United States and it is often a mandatory condition of probation or parole. In Texas, a state appellate court has upheld the testing of sex offenders under community supervision and has also upheld written statements given by sex offenders if they have committed a further offense with new victims. These statements are then used when a motion is filed to revoke probation and the probationer may then be sentenced to prison for having violated his or her probation.
A significant number of Federal appeals courts have upheld polygraph testing for Federal probationers as well. The most recent decision was by the Second Circuit Court of Appeals regarding a New York sex offender.
The UK will soon allow compulsory polygraph tests for convicted sex offenders released on license.[45][46]
# Polygraph in popular culture
Lie detection has a long history in mythology and fairy tales; the polygraph has allowed modern fiction to use a device more easily seen as scientific and plausible. Notable instances of polygraph usage include uses in crime and espionage themed television shows and some daytime television talk shows, cartoons and films. The most notable polygraph TV show is Lie Detector (TV series)|Lie Detector, which first aired in the 1950s created and hosted by Ralph Andrews. Then in the 1960s Ralph produced a series of specials hosted by Melvin Belli, then in the 1970s hosted by Jack Anderson. In 1998 TV producer Mark Phillips with his Mark Phillips Philms & Telephision put Lie Detector back on the air on the FOX Network -- on that program Dr. Ed Gelb with host Marcia Clark cleared Mark Fuhrman from the allegation that he "planted the bloody glove." Later Phillips produced Lie Detector as a series for PAX/ION -- some of the guests included Paula Jones, Reverend Paul Crouch accuser Lonny Ford, Ben Rowling, Jeff Gannon and Swift Boat Vet Steve Garner.
FOX has taken this one step further with their game show The Moment of Truth (US game show)|The Moment of Truth which pits people's honesty against their own sense of modesty, propriety, etc. Contestants are given a polygraph test administered by a polygraph expert in a pre-screening session answering over 50 questions. Later they must sit in front of a studio audience including their friends & family for the televised portion of the show. There they need only answer 21 answers truthfully "as determined by the polygraph" to win $500,000. The questions get more personal and/or more revealing as they advance. Most polygraph experts caution that the polygraph techniques used on Moment of Truth do not conform to any known or accepted methods of polygraphy.[citation needed]
Daytime talk shows, such as Maury Povich, frequently uses lie detectors in order to tell if someone is cheating on their significant other.
In the movie Ocean's 13, one of the characters beats a polygraph test by stepping on a tack when answering truthfully, which supposedly raises the polygraph's readings for the truthful answers so they equal to the deceptive ones.
In episode 109 of the USA popular science show Mythbusters, they attempted to fool the polygraph by using pain to try to increase the readings when answering truthfully (so the machine will supposedly interpret the truthful and non-truthful answers as the same.) They also attempted to fool the polygraph by thinking happy thoughts when lying and thinking stressful thoughts when telling the truth to try to confuse the machine. However, neither technique was successful for a number of reasons. Michael Martin correctly identified each guilty and innocent subject. The show also noted the widely held opinion that, when done properly, polygraphs are correct 80-99% of the time.[47] | https://www.wikidoc.org/index.php/Polygraph | |
3e83ef45c50006e68190d5fad18b028c1d8b0698 | wikidoc | Polyimide | Polyimide
Polyimide (sometimes abbreviated PI) is a polymer of imide monomers. The structure of imide is as shown below.
There are two general types of polyimides. One type, so-called linear polyimides, are made by combining imides into long chains. Aromatic heterocyclic polyimides are the other usual kind, where R′ and R″ are two carbon atoms of an aromatic ring. Examples of polyimide films include Apical, Kapton and Kaptrex. Polyimide parts and shapes include Meldin, Vespel and Plavis. Polyimides have been in mass production since 1955.
Polyimide is often used in the electronics industry for flexible cables and as an insulating film on magnet wire. For example, in a laptop computer, the cable that connects the main logic board to the display (which must flex every time the laptop is opened or closed) is often a polyimide base with copper conductors. The semiconductor industry uses polyimide as a high-temperature adhesive.
# Notes
- ↑ Deformation temperature at 10kN needle load, source: A.K. vam der Vegt & L.E. Govaert, Polymeren,van keten tot kunstof, ISBN 90-407-2388-5
See also: Polyamide
de:Polyimid
id:Poliimid | Polyimide
Polyimide (sometimes abbreviated PI) is a polymer of imide monomers. The structure of imide is as shown below.
There are two general types of polyimides. One type, so-called linear polyimides, are made by combining imides into long chains. Aromatic heterocyclic polyimides are the other usual kind, where R′ and R″ are two carbon atoms of an aromatic ring. Examples of polyimide films include Apical, Kapton and Kaptrex. Polyimide parts and shapes include Meldin, Vespel and Plavis. Polyimides have been in mass production since 1955.
Polyimide is often used in the electronics industry for flexible cables and as an insulating film on magnet wire. For example, in a laptop computer, the cable that connects the main logic board to the display (which must flex every time the laptop is opened or closed) is often a polyimide base with copper conductors. The semiconductor industry uses polyimide as a high-temperature adhesive.
# Notes
- ↑ Deformation temperature at 10kN needle load, source: A.K. vam der Vegt & L.E. Govaert, Polymeren,van keten tot kunstof, ISBN 90-407-2388-5
See also: Polyamide
Template:Polymer-stub
de:Polyimid
id:Poliimid | https://www.wikidoc.org/index.php/Polyimide | |
9ed14719dba05b3b574fb83bc3f808d6b73650b3 | wikidoc | Polymyxin | Polymyxin
Polymyxins are cationic detergent antibiotics, with a general structure of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. Polymyxins have a bactericidal effect on Gram-negative bacilli, especially on Pseudomonas andcoliform organisms. Polymyxin antibiotics are highly neurotoxic and nephrotoxic, and very poorly absorbed from the gastrointestinal tract. Polymyxins also have antifungal activity.
Well known examples:
- Colistin
- Polymyxin B
- Surfactin
Polymyxin acts as an antibiotic by damaging the cytoplasmic membrane of bacteria.
Also polymyxins biological source is Bacillius polymyxa.
Polymyxins are antibiotics, with a general structure consisting of a cyclic
peptide with a long hydrophobic tail. They disrupt the structure of the
bacterial cell membrane by interacting with its phospholipids. They are
produced by nonribosomal peptide synthetase systems in Gram-positive bacteria such as Paenibacillus polymyxa and are
selectively toxic for Gram-negative bacteria due to their specificity for
the lipopolysaccharide molecule that exists within many Gram-negative outer membranes.
Polymyxins B and E (also known as colistin) are used in the
treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently.
Polymyxin M is also known as "mattacin".
# Mechanism of action
After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative
bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic
tail is important in causing membrane damage, suggesting a detergent-like
mode of action.
Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide,
which still binds to LPS but no longer kills the bacterial cell. However, it
still detectably increases the permeability of the bacterial cell wall to other
antibiotics, indicating that it still causes some degree of membrane
disorganization.
Gram-negative bacteria can develop resistance to polymyxins through various
modifications of the LPS structure that inhibit the binding of polymyxins to
LPS.
# Clinical use
Polymyxin antibiotics are relatively neurotoxic and nephrotoxic and are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multidrug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.
Polymyxins are not absorbed from the gastrointestinal tract, and, therefore, another route of administration must be chosen, e.g., parenteral (often intravenously) or by inhalation (unless perhaps
the target is bacteria in the gastrointestinal tract).
Polymyxins have less effect on Gram positive organisms, and are sometimes combined with other agents (as with Trimethoprim/polymyxin) to broaden the effective spectrum.
# Use in biomedical research
Polymyxins are used to neutralize or absorb LPS, which contaminates samples that are intended for use in, e.g., immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and, therefore, distort experimental results.
By increasing permeability of the bacterial membrane system, polymyxin is also used in clinical work to increase release of secreted toxins, such as Shiga toxin from Escherichia coli. | Polymyxin
Polymyxins are cationic detergent antibiotics, with a general structure of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. Polymyxins have a bactericidal effect on Gram-negative bacilli, especially on Pseudomonas andcoliform organisms. Polymyxin antibiotics are highly neurotoxic and nephrotoxic, and very poorly absorbed from the gastrointestinal tract. Polymyxins also have antifungal activity.
Well known examples:
- Colistin
- Polymyxin B
- Surfactin
Polymyxin acts as an antibiotic by damaging the cytoplasmic membrane of bacteria.
Also polymyxins biological source is Bacillius polymyxa.
Polymyxins are antibiotics,[1] with a general structure consisting of a cyclic
peptide with a long hydrophobic tail. They disrupt the structure of the
bacterial cell membrane by interacting with its phospholipids. They are
produced by nonribosomal peptide synthetase systems in Gram-positive bacteria such as Paenibacillus polymyxa[2] and are
selectively toxic for Gram-negative bacteria due to their specificity for
the lipopolysaccharide molecule that exists within many Gram-negative outer membranes.
Polymyxins B and E (also known as colistin) are used in the
treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently.[3]
Polymyxin M is also known as "mattacin".[4]
# Mechanism of action
After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative
bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic
tail is important in causing membrane damage, suggesting a detergent-like
mode of action.
Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide,
which still binds to LPS but no longer kills the bacterial cell. However, it
still detectably increases the permeability of the bacterial cell wall to other
antibiotics, indicating that it still causes some degree of membrane
disorganization.
Gram-negative bacteria can develop resistance to polymyxins through various
modifications of the LPS structure that inhibit the binding of polymyxins to
LPS.[5]
# Clinical use
Polymyxin antibiotics are relatively neurotoxic and nephrotoxic[6] and are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multidrug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.
Polymyxins are not absorbed from the gastrointestinal tract, and, therefore, another route of administration must be chosen, e.g., parenteral (often intravenously) or by inhalation (unless perhaps
the target is bacteria in the gastrointestinal tract).
Polymyxins have less effect on Gram positive organisms, and are sometimes combined with other agents (as with Trimethoprim/polymyxin) to broaden the effective spectrum.
# Use in biomedical research
Polymyxins are used to neutralize or absorb LPS, which contaminates samples that are intended for use in, e.g., immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and, therefore, distort experimental results.
By increasing permeability of the bacterial membrane system, polymyxin is also used in clinical work to increase release of secreted toxins, such as Shiga toxin from Escherichia coli.[7] | https://www.wikidoc.org/index.php/Polymyxin | |
a6534708800ed055e6a740161ccceebe0fb9bd1d | wikidoc | Polywater | Polywater
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
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Polywater was a hypothetical polymerized form of water that was the subject of much scientific controversy during the late 1960s. It was later found to be illusory, and today is used as an example of pathological science.
# Background
The Soviet physicist Nikolai Fedyakin, working at a small government research lab in Kostroma, Russia, had performed measurements on the properties of water that had been condensed in, or repeatedly forced through, narrow quartz capillary tubes. Some of these experiments resulted in what was seemingly a new form of water with a higher boiling point, lower freezing point, and much higher viscosity than ordinary water, about that of a syrup.
Boris Derjaguin, director of the laboratory for surface physics at the Institute for Physical Chemistry in Moscow, heard about Fedyakin's experiments. He improved on the method to produce the new water, and though he still produced very small quantities of this mysterious material, he did so substantially faster than Fedyakin did. Investigations of the material properties showed a substantially lower freezing point of −40 °C or less, a boiling point of 150 °C or greater, a density of approx. 1.1 to 1.2 g/cm³, and increased expansion with increasing temperature. The results were published in Soviet science journals, and short summaries were published in Chemical Abstracts in English, but Western scientists took no notice of the work.
In 1966, Derjaguin travelled to England for the "Discussions of the Faraday Society" in Nottingham. There he presented the work again, and this time English scientists took note of what he referred to as anomalous water. English scientists then started researching the effect as well, and by 1968 it was also under study in the United States.
A scientific furor followed. Some experimentalists were able to reproduce Derjaguin's findings, while others failed. Several theories were advanced to explain the phenomenon. Some proposed that it was the cause for increasing resistance on trans-Atlantic phone cables, while others predicted that if polywater were to contact ordinary water, it would convert that water into polywater, echoing the doomsday scenario in Kurt Vonnegut's novel Cat's Cradle.
During this time several people questioned the authenticity of what had come to be known in the West as polywater. The main concern was contamination of the water, but the papers went to great lengths to note the care taken to avoid this. However, Denis Rousseau of Bell Labs undertook to experiment with his own sweat after playing a handball game at the lab, and found it had identical properties. He then published a paper suggesting that polywater was nothing more than water with small amounts of biological impurities.
Another wave of research followed, this time more tightly controlled. Invariably the polywater could no longer be made. Chemical analysis invariably found that samples of polywater were contaminated with other substances (explaining the changes in melting and boiling points), and examination of polywater via electron microscopy showed that it also contained small particles of various solids from silicon to phospholipids, explaining its greater viscosity.
When the experiments that had produced polywater were repeated with thoroughly cleaned glassware, the anomalous properties of the resulting water vanished, and even the scientists who had originally advanced the case for polywater agreed that it did not exist. This took a few years longer in the Soviet Union, where scientists still clung to the idea.
Denis Rousseau used polywater as a classic example of pathological science, and has since written on other examples as well.
# In fiction
Polywater made appearances in the Star Trek science fiction universe, first appearing in the original series episode "The Naked Time" and then in The Next Generation episode "The Naked Now".
In its Star Trek appearances, polywater formed under certain extreme gravimetric conditions - such as the breakup of a planet or the collapse of a red supergiant star into a white dwarf. When introduced into the systems of humanoids, polywater intoxication could occur if the polywater acquired carbon from the body, acting on the brain in ways similar to extreme alcohol intoxication. It could also interact with Soong type androids with positronic brains, having affected Data during the polywater contamination of 2364. This polywater intoxication was known within the series as the Psi 2000 virus (in truth, not strictly a virus), named after the planet where it was first discovered.
The story "Polywater Doodle" by Howard L. Myers appeared in the February, 1971 issue of Analog Science Fiction/Science Fact. | Polywater
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Polywater was a hypothetical polymerized form of water that was the subject of much scientific controversy during the late 1960s. It was later found to be illusory, and today is used as an example of pathological science.
# Background
The Soviet physicist Nikolai Fedyakin, working at a small government research lab in Kostroma, Russia, had performed measurements on the properties of water that had been condensed in, or repeatedly forced through, narrow quartz capillary tubes. Some of these experiments resulted in what was seemingly a new form of water with a higher boiling point, lower freezing point, and much higher viscosity than ordinary water, about that of a syrup.
Boris Derjaguin, director of the laboratory for surface physics at the Institute for Physical Chemistry in Moscow, heard about Fedyakin's experiments. He improved on the method to produce the new water, and though he still produced very small quantities of this mysterious material, he did so substantially faster than Fedyakin did. Investigations of the material properties showed a substantially lower freezing point of −40 °C or less, a boiling point of 150 °C or greater, a density of approx. 1.1 to 1.2 g/cm³, and increased expansion with increasing temperature. The results were published in Soviet science journals, and short summaries were published in Chemical Abstracts in English, but Western scientists took no notice of the work.
In 1966, Derjaguin travelled to England for the "Discussions of the Faraday Society" in Nottingham. There he presented the work again, and this time English scientists took note of what he referred to as anomalous water. English scientists then started researching the effect as well, and by 1968 it was also under study in the United States.
A scientific furor followed. Some experimentalists were able to reproduce Derjaguin's findings, while others failed. Several theories were advanced to explain the phenomenon. Some proposed that it was the cause for increasing resistance on trans-Atlantic phone cables, while others predicted that if polywater were to contact ordinary water, it would convert that water into polywater, echoing the doomsday scenario in Kurt Vonnegut's novel Cat's Cradle.
During this time several people questioned the authenticity of what had come to be known in the West as polywater. The main concern was contamination of the water, but the papers went to great lengths to note the care taken to avoid this. However, Denis Rousseau of Bell Labs undertook to experiment with his own sweat after playing a handball game at the lab, and found it had identical properties. He then published a paper suggesting that polywater was nothing more than water with small amounts of biological impurities.
Another wave of research followed, this time more tightly controlled. Invariably the polywater could no longer be made. Chemical analysis invariably found that samples of polywater were contaminated with other substances (explaining the changes in melting and boiling points), and examination of polywater via electron microscopy showed that it also contained small particles of various solids from silicon to phospholipids, explaining its greater viscosity.
When the experiments that had produced polywater were repeated with thoroughly cleaned glassware, the anomalous properties of the resulting water vanished, and even the scientists who had originally advanced the case for polywater agreed that it did not exist. This took a few years longer in the Soviet Union, where scientists still clung to the idea.
Denis Rousseau used polywater as a classic example of pathological science, and has since written on other examples as well.[1]
# In fiction
Polywater made appearances in the Star Trek science fiction universe, first appearing in the original series episode "The Naked Time" and then in The Next Generation episode "The Naked Now".
In its Star Trek appearances, polywater formed under certain extreme gravimetric conditions - such as the breakup of a planet or the collapse of a red supergiant star into a white dwarf. When introduced into the systems of humanoids, polywater intoxication could occur if the polywater acquired carbon from the body, acting on the brain in ways similar to extreme alcohol intoxication. It could also interact with Soong type androids with positronic brains, having affected Data during the polywater contamination of 2364. This polywater intoxication was known within the series as the Psi 2000 virus (in truth, not strictly a virus), named after the planet where it was first discovered.
The story "Polywater Doodle" by Howard L. Myers appeared in the February, 1971 issue of Analog Science Fiction/Science Fact. | https://www.wikidoc.org/index.php/Polywater | |
968fd4510607aafb650fa28477f89e06b52d05e3 | wikidoc | Pomovirus | Pomovirus
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# Overview
The Pomovirus is a genus of a virus with no family. Virions are non-enveloped, elongated and rod-shaped with a length of 100-300 nm and a width of 18-20 nm with helical spirals on both ends. The genome is a single piece of non-segmented linear, positive-sense, single-stranded RNA. The name of the genus is derived from its type species, Potato mop-top virus, giving rise to Pomovirus..
Species in this genus include:
- Beet soil-borne virus
- Beet virus Q
- Broad bean necrosis virus
- Potato mop-top virus | Pomovirus
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# Overview
The Pomovirus is a genus of a virus with no family. Virions are non-enveloped, elongated and rod-shaped with a length of 100-300 nm and a width of 18-20 nm with helical spirals on both ends. The genome is a single piece of non-segmented linear, positive-sense, single-stranded RNA. The name of the genus is derived from its type species, Potato mop-top virus, giving rise to Pomovirus.[1].
Species in this genus include:
- Beet soil-borne virus
- Beet virus Q
- Broad bean necrosis virus
- Potato mop-top virus | https://www.wikidoc.org/index.php/Pomovirus | |
142834616278f78abc164f609efa091d455ddd45 | wikidoc | Poppy tea | Poppy tea
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# Overview
Poppy tea is a narcotic analgesic tea which is brewed from the dried parts of the Papaver somniferum plant. It has been consumed for its psychoactive effects for as long as the poppy has been cultivated. It is depicted both in Asian literature and Western literature, such as in opium dens. In some places, preparation of tea may be preferred to opium as the latex of the plant (itself the primary component of opium) is illegal. In the Netherlands, all parts of the Papaver Somniferum after harvesting(except for the seeds) are illegal by law, as they are List I drugs of the Opium Law. Because of use for decorative purposes, the trade in, and possession of dried Papaver Somniferum is not actively prosecuted. Trade in, or possession of dried Papaper Somniferum with the intention of drug use can be prosecuted, although this is very unlikely. For this reason, it's an alternative to pharmaceutical opioids, which are highly regulated in the Netherlands, while dried Papaver Somniferum is easily obtainable as it's commonly available for decorative use. In the United States it is legal to purchase poppy seeds, dried pods, and in some cases to grow the Papaver somniferum variety of poppies, but intentionally using a legal purchase (such as seeds) to concentrate any usable opioid product is illegal.
Poppy tea contains two groups of alkaloids: phenanthrenes (including morphine and codeine) and benzylisoquinolines (including papaverine). Of these, morphine is the most prevalent comprising 8%-14% of the total. Its effects derive from the fact that it binds to and activates mu opioid receptors in the brain, spinal cord, stomach and intestine.
# Preparation and consumption
The tea may be prepared from either the seed pods or the seeds themselves. Dried poppy pods are first crushed up into a fine straw like substance for efficient extraction. When reduced to small pieces they form poppy straw, which is steeped in hot water that has been slightly acidified with vinegar or citric acid. After steeping for a few minutes, the mixture is strained and the brown liquid is set aside for consumption.
When the tea is drunk, its effects begin after about 30 minutes, lasting up to 8 hours. It is intensely bitter and some users add other flavorings to the tea. Grapefruit juice may also inhibit liver enzyme activation, thus increasing the strength and duration of the opiate effects.
The tea is also sometimes evaporated over a very low heat to make a thick, concentrated liquid or a dry powder, and some users put this material into gel caps to allow for dosage to be measured more carefully.
Although oral administration is the most common, dried poppy tea can also be snorted or smoked. However, many users report unpleasant side effects from these methods because of the non-active and potentially irritating substances which are present in addition to the alkaloids. Dried poppy tea is not the same as opium, as the former is made from the whole plant while the latter is made from exuded latex alone. Some users bypass the tea stage and simply add poppy straw to a food such as yogurt. This method partially masks the taste but may lead to more gastric discomfort than consuming tea or dried tea.
The pods may also be used in the green (undried) state to make tea. It has often been written that the tea may only be procured from the dried pods. This is not an accurate statement, as the green pods are as viable for the production of an excellent tea as much as the dried pods. The advantage of dried pods is more crucial in the production of large quantities of pure opium from whole pods. This is due to the fact that it is easier to grind the dried pods into a smaller mass that is easier to work with in a large scale production. In contrast, the green pods tend to "gum up" and, thus, are not easily reduced into the small particles attained by grinding dried pods into a powder from which one may extract the maximum amount of the active alkaloids per pod.
To make a tea from the green pods all that is necessary is a blender, hot water, stove and sauce pan. It is crucial to blend the green pods into a fine mash in the blender, so that the maximum amount of alkaloids can be extracted. Then the mash should be heated over medium heat with three pods for every 8 oz. of water. This proportion may vary in relation to the strength of the poppy pods or an individuals tolerance to the drug, but is effective in most cases. Never allow the mash to boil, as this may destroy the alkaloids necessary to make a potent tea. Lastly, mix the heated mash with lemon and honey and steep for 15 minutes. The resulting beverage will yield immense pleasure and/or pain relief.
# Effects
Effects vary widely depending on dosage (amount of poppy straw used, alkaloid content of poppies and the quality of extraction), on individual sensitivity and on any opiate tolerance which has built up. In varying degrees, the tea's contents are the base from which all opiates (natural, semi-synthetic & synthetic) are derived from. The user can expect a warming sensation of the skin and body during onset. Since many of the opioid receptors are located in the spinal chord (CNC) as well as in the the digestional tract, the user describes the ability tofeel the intestinal tract with the sensation of lightness, and pleasure. An elevated mood change follows, along with a state of extreme euphoria and well being. Pupils tend to constrict, and the face, neck, and outer extremeties flush. Since opioids are known to release histamine, the user becomes itchy, towards the time the liver starts to metabolize the alkaloids.
# Side effects and tolerance
Side effects increase with dosage and include sleepiness, mild stomachache, lethargy, itching, slowed breathing and nausea. Nausea can be attributed to the presence of noscapine and is more common in first-time or inexperienced users. At high doses, the side effects are dangerous and can cause death through cessation of breathing or choking on vomit.
As with any opiate, frequent use results in tolerance and dependence. Chemical dependency builds up after one to two weeks of daily usage. Frequent use followed by abrupt abstinence gives rise to withdrawal symptoms including leg and abdominal cramps, vomit, diarrhea, headache, insomnia, cravings and anxiety. Physical symptoms of withdrawal usually fade after 4-10 days but cravings and psychological dependence may continue for longer.
# Overdose
It is relatively easy to overdose with poppy tea as the recreational dose is not greatly below the dose at which side effects become unpleasant or dangerous. Experienced users take a modest initial dose followed by small amounts over an extended period of time in order to titrate up to the desired level.
A case of fatal overdose in 2003 has been reported on a website authored by the victim's parents. The site alleges that a sample of poppy seed tea was sent for laboratory analysis. This victim is reported to have used 3.5 lbs of poppy seeds in his tea preparation as on several previous occasions. The concentration of morphine in the tea was shown to be around 250 μg/ml and the amount of morphine which had been consumed by the individual was around 500 mg. This is about five times the lethal oral dose for an individual without opiate tolerance. ABC News reported on the incident in January 2008. | Poppy tea
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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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.
# Overview
Poppy tea is a narcotic analgesic tea which is brewed from the dried parts of the Papaver somniferum plant. It has been consumed for its psychoactive effects for as long as the poppy has been cultivated. It is depicted both in Asian literature and Western literature, such as in opium dens. In some places, preparation of tea may be preferred to opium as the latex of the plant (itself the primary component of opium) is illegal. In the Netherlands, all parts of the Papaver Somniferum after harvesting(except for the seeds) are illegal by law, as they are List I drugs of the Opium Law. Because of use for decorative purposes, the trade in, and possession of dried Papaver Somniferum is not actively prosecuted. Trade in, or possession of dried Papaper Somniferum with the intention of drug use can be prosecuted, although this is very unlikely. For this reason, it's an alternative to pharmaceutical opioids, which are highly regulated in the Netherlands, while dried Papaver Somniferum is easily obtainable as it's commonly available for decorative use. In the United States it is legal to purchase poppy seeds, dried pods, and in some cases to grow the Papaver somniferum variety of poppies, but intentionally using a legal purchase (such as seeds) to concentrate any usable opioid product is illegal.
Poppy tea contains two groups of alkaloids: phenanthrenes (including morphine and codeine) and benzylisoquinolines (including papaverine). Of these, morphine is the most prevalent comprising 8%-14% of the total. Its effects derive from the fact that it binds to and activates mu opioid receptors in the brain, spinal cord, stomach and intestine.
# Preparation and consumption
The tea may be prepared from either the seed pods or the seeds themselves. Dried poppy pods are first crushed up into a fine straw like substance for efficient extraction. When reduced to small pieces they form poppy straw, which is steeped in hot water that has been slightly acidified with vinegar or citric acid. After steeping for a few minutes, the mixture is strained and the brown liquid is set aside for consumption.
When the tea is drunk, its effects begin after about 30 minutes, lasting up to 8 hours. It is intensely bitter and some users add other flavorings to the tea. Grapefruit juice may also inhibit liver enzyme activation, thus increasing the strength and duration of the opiate effects.
The tea is also sometimes evaporated over a very low heat to make a thick, concentrated liquid or a dry powder, and some users put this material into gel caps to allow for dosage to be measured more carefully.
Although oral administration is the most common, dried poppy tea can also be snorted or smoked. However, many users report unpleasant side effects from these methods because of the non-active and potentially irritating substances which are present in addition to the alkaloids. Dried poppy tea is not the same as opium, as the former is made from the whole plant while the latter is made from exuded latex alone. Some users bypass the tea stage and simply add poppy straw to a food such as yogurt. This method partially masks the taste but may lead to more gastric discomfort than consuming tea or dried tea.
The pods may also be used in the green (undried) state to make tea. It has often been written that the tea may only be procured from the dried pods. This is not an accurate statement, as the green pods are as viable for the production of an excellent tea as much as the dried pods. The advantage of dried pods is more crucial in the production of large quantities of pure opium from whole pods. This is due to the fact that it is easier to grind the dried pods into a smaller mass that is easier to work with in a large scale production. In contrast, the green pods tend to "gum up" and, thus, are not easily reduced into the small particles attained by grinding dried pods into a powder from which one may extract the maximum amount of the active alkaloids per pod.
To make a tea from the green pods all that is necessary is a blender, hot water, stove and sauce pan. It is crucial to blend the green pods into a fine mash in the blender, so that the maximum amount of alkaloids can be extracted. Then the mash should be heated over medium heat with three pods for every 8 oz. of water. This proportion may vary in relation to the strength of the poppy pods or an individuals tolerance to the drug, but is effective in most cases. Never allow the mash to boil, as this may destroy the alkaloids necessary to make a potent tea. Lastly, mix the heated mash with lemon and honey and steep for 15 minutes. The resulting beverage will yield immense pleasure and/or pain relief.
# Effects
Effects vary widely depending on dosage (amount of poppy straw used, alkaloid content of poppies and the quality of extraction), on individual sensitivity and on any opiate tolerance which has built up. In varying degrees, the tea's contents are the base from which all opiates (natural, semi-synthetic & synthetic) are derived from. The user can expect a warming sensation of the skin and body during onset. Since many of the opioid receptors are located in the spinal chord (CNC) as well as in the the digestional tract, the user describes the ability tofeel the intestinal tract with the sensation of lightness, and pleasure. An elevated mood change follows, along with a state of extreme euphoria and well being. Pupils tend to constrict, and the face, neck, and outer extremeties flush. Since opioids are known to release histamine, the user becomes itchy, towards the time the liver starts to metabolize the alkaloids.
# Side effects and tolerance
Side effects increase with dosage and include sleepiness, mild stomachache, lethargy, itching, slowed breathing and nausea. Nausea can be attributed to the presence of noscapine and is more common in first-time or inexperienced users. At high doses, the side effects are dangerous and can cause death through cessation of breathing or choking on vomit.
As with any opiate, frequent use results in tolerance and dependence. Chemical dependency builds up after one to two weeks of daily usage. Frequent use followed by abrupt abstinence gives rise to withdrawal symptoms including leg and abdominal cramps, vomit, diarrhea, headache, insomnia, cravings and anxiety. Physical symptoms of withdrawal usually fade after 4-10 days but cravings and psychological dependence may continue for longer.
# Overdose
It is relatively easy to overdose with poppy tea as the recreational dose is not greatly below the dose at which side effects become unpleasant or dangerous. Experienced users take a modest initial dose followed by small amounts over an extended period of time in order to titrate up to the desired level.
A case of fatal overdose in 2003 has been reported on a website authored by the victim's parents. The site alleges that a sample of poppy seed tea was sent for laboratory analysis. This victim is reported to have used 3.5 lbs of poppy seeds in his tea preparation as on several previous occasions. The concentration of morphine in the tea was shown to be around 250 μg/ml and the amount of morphine which had been consumed by the individual was around 500 mg.[1] This is about five times the lethal oral dose for an individual without opiate tolerance.[2] ABC News reported on the incident in January 2008.[3] | https://www.wikidoc.org/index.php/Poppy_tea | |
d0eb8b7e8bef0572cda6e6ff8bf3244bc4445738 | wikidoc | Porphyrin | Porphyrin
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# Overview
A porphyrin is a heterocyclic macrocycle derived from four pyrrole-like subunits interconnected via their α carbon atoms via methine bridges (=CH-). The macrocycle, therefore, is a highly conjugated system, and is consequently deeply coloured—the name porphyrin comes from a Greek word for purple. The macrocycle has 22 pi electrons. The parent porphyrin is porphine, and substituted porphines are called porphyrins. Many porphyrins occur in nature, such as in green leaves and red blood cells, and in bio-inspired synthetic catalysts and devices.
# Complexes of porphyrins and related molecules
Porphyrins bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+, resides in the central N4 cavity formed by the loss of two protons. Most metals can be inserted. A schematic equation for these syntheses is shown:
A porphyrin in which no metal is inserted in its cavity is sometimes called a free base. Some iron-containing porphyrins are called hemes; and heme-containing proteins, or hemoproteins, are found extensively in Nature. Hemoglobin and myoglobin are two O2-binding proteins that contain iron porphyrins.
Related to porphyrins are several other heterocycles, including corrins, chlorins, bacteriochlorophylls, and corphins. Chlorins (2,3-dihydroporphyrin) are more reduced, that contain more hydrogen, than porphyrins, featuring a pyrroline subunit. This structure occurs in chlorophyll. Replacement of two of the four pyrrolic subunits with pyrrolinic subunits results in either a bacteriochlorin (as found in some photosynthetic bacteria) or an isobacteriochlorin, depending on the relative positions of the reduced rings. Some porphyrin derivatives follow Hückel's rule, but most do not.
# Laboratory synthesis
One of the more common syntheses for porphyrins is based on work by Paul Rothemund. His techniques underpin more modern syntheses such as those described by Alder and Longo. The synthesis of simple porphyrins such as meso-tetraphenylporphyrin is also commonly done in university teaching labs.
In this method, porphyrins are assembled from pyrrole and substituted aldehydes. Acidic conditions are essential; formic acid, acetic acid, and propionic acid are typical reaction solvents, or p-toluenesulfonic acid can be used with a non-acidic solvent. Lewis acids such as boron trifluoride etherate and ytterbium triflate have also been known to catalyse porphyrin formation. A large amount of side product is formed and is removed, usually by chromatography.
# Biosynthesis
The "committed step" for porphyrin biosynthesis is the formation of D-aminolevulinic acid (dALA) by the reaction of the amino acid glycine and succinyl-CoA, from the citric acid cycle. Two molecules of dALA combine to give porphobilinogen (PBG), which contains a pyrrole ring. Four PBGs are then combined through deamination into hydroxymethyl bilane (HMB), which is hydrolysed to form the circular tetrapyrrole uroporphyrinogen III. This molecule undergoes a number of further modifications. Intermediates are used in different species to form particular substances, but, in humans, the main end-product protoporphyrin IX is combined with iron to form heme. Bile pigments are the breakdown products of heme.
The following scheme summarizes the biosynthesis of porphyrins, with references by EC number and the OMIM database. The porphyria associated with the deficiency of each enzyme is also shown:
# Applications
Although natural porphyin complexes are essential for life, synthetic porphyrins and their complexes have limited utility. Complexes of meso-tetraphenylporphyrin, e.g. the iron-(III) chloride complex (TPPFeCl) catalyse a variety of reactions in organic chemistry, but none are of practical value. Porphyrin-based compounds are of interest in molecular electronics and supramolecular building blocks. Phthalocyanines, which are structurally related to porphyrins, are used in commerce as dyes and catalysts.
Synthetic porphyrin dyes that are incorporated in the design of solar cells are the subject of ongoing research. See Dye-sensitized solar cells.
# Supramolecular chemistry
Porphyrins are often used to construct structures in supramolecular chemistry. These systems take advantage of the Lewis acidity of the metal, typically zinc. An example of a host-guest complex that was constructed from a macrocycle composed of four porphyrins. A guest-free base porphyrin is bound to the center by coordination with its four pyridine sustituents. | Porphyrin
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A porphyrin is a heterocyclic macrocycle derived from four pyrrole-like subunits interconnected via their α carbon atoms via methine bridges (=CH-). The macrocycle, therefore, is a highly conjugated system, and is consequently deeply coloured—the name porphyrin comes from a Greek word for purple. The macrocycle has 22 pi electrons. The parent porphyrin is porphine, and substituted porphines are called porphyrins. Many porphyrins occur in nature, such as in green leaves and red blood cells, and in bio-inspired synthetic catalysts and devices.
# Complexes of porphyrins and related molecules
Porphyrins bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+, resides in the central N4 cavity formed by the loss of two protons. Most metals can be inserted. A schematic equation for these syntheses is shown:
A porphyrin in which no metal is inserted in its cavity is sometimes called a free base. Some iron-containing porphyrins are called hemes; and heme-containing proteins, or hemoproteins, are found extensively in Nature. Hemoglobin and myoglobin are two O2-binding proteins that contain iron porphyrins.
Related to porphyrins are several other heterocycles, including corrins, chlorins, bacteriochlorophylls, and corphins. Chlorins (2,3-dihydroporphyrin) are more reduced, that contain more hydrogen, than porphyrins, featuring a pyrroline subunit. This structure occurs in chlorophyll. Replacement of two of the four pyrrolic subunits with pyrrolinic subunits results in either a bacteriochlorin (as found in some photosynthetic bacteria) or an isobacteriochlorin, depending on the relative positions of the reduced rings. Some porphyrin derivatives follow Hückel's rule, but most do not.
# Laboratory synthesis
One of the more common syntheses for porphyrins is based on work by Paul Rothemund.[1][2] His techniques underpin more modern syntheses such as those described by Alder and Longo.[3] The synthesis of simple porphyrins such as meso-tetraphenylporphyrin is also commonly done in university teaching labs.[4]
In this method, porphyrins are assembled from pyrrole and substituted aldehydes. Acidic conditions are essential; formic acid, acetic acid, and propionic acid are typical reaction solvents, or p-toluenesulfonic acid can be used with a non-acidic solvent. Lewis acids such as boron trifluoride etherate and ytterbium triflate have also been known to catalyse porphyrin formation. A large amount of side product is formed and is removed, usually by chromatography.
# Biosynthesis
The "committed step" for porphyrin biosynthesis is the formation of D-aminolevulinic acid (dALA) by the reaction of the amino acid glycine and succinyl-CoA, from the citric acid cycle. Two molecules of dALA combine to give porphobilinogen (PBG), which contains a pyrrole ring. Four PBGs are then combined through deamination into hydroxymethyl bilane (HMB), which is hydrolysed to form the circular tetrapyrrole uroporphyrinogen III. This molecule undergoes a number of further modifications. Intermediates are used in different species to form particular substances, but, in humans, the main end-product protoporphyrin IX is combined with iron to form heme. Bile pigments are the breakdown products of heme.
The following scheme summarizes the biosynthesis of porphyrins, with references by EC number and the OMIM database. The porphyria associated with the deficiency of each enzyme is also shown:
# Applications
Although natural porphyin complexes are essential for life, synthetic porphyrins and their complexes have limited utility. Complexes of meso-tetraphenylporphyrin, e.g. the iron-(III) chloride complex (TPPFeCl) catalyse a variety of reactions in organic chemistry, but none are of practical value. Porphyrin-based compounds are of interest in molecular electronics and supramolecular building blocks. Phthalocyanines, which are structurally related to porphyrins, are used in commerce as dyes and catalysts.
Synthetic porphyrin dyes that are incorporated in the design of solar cells are the subject of ongoing research. See Dye-sensitized solar cells.
# Supramolecular chemistry
Porphyrins are often used to construct structures in supramolecular chemistry. These systems take advantage of the Lewis acidity of the metal, typically zinc. An example of a host-guest complex that was constructed from a macrocycle composed of four porphyrins.[5] A guest-free base porphyrin is bound to the center by coordination with its four pyridine sustituents. | https://www.wikidoc.org/index.php/Porphyrin | |
c1655e19b963127719f801aaab180c638a91d6e2 | wikidoc | Postnatal | Postnatal
# Background
Postnatal (Latin for 'after birth') is the period beginning immediately after the birth of a child and extending for about six weeks. The period is also known as postpartum period and, less commonly, puerperium.
Biologically, it is the time after birth, a time in which the mother's body, including hormone levels and uterus size, return to prepregnancy conditions. Lochia is post-partum vaginal discharge, containing blood, mucus, and placental tissue.
During the first stages of this period, the newborn also starts his or her adaptation to extrauterine life, the most significant physiological transition until death.
In scientific literature the term is commonly abbreviated to PX. So that 'day P5' should be read as 'the fifth day after birth'.
# Woman care
A woman in the Western world who is delivering in a hospital may leave the hospital as early as 6 hours postpartum, though the average for spontaneous vaginal delivery (SVD) is 1-2 days, and the average caesarean section postnatal stay is 3-4 days.
During this time bleeding, bowel and bladder function, and baby care are monitored.
## Physical
The mother is assessed for tears, and is sutured if necessary. Also, she may suffer from constipation or hemorrhoids, both of which would be managed. The bladder is also assessed for infection, retention and any problems in the muscles.
The major focus of postpartum care is ensuring that the woman is healthy and capable of taking care of her newborn, equipped with all the information she needs about breastfeeding, reproductive health and contraception, and the imminent life adjustment.
Some medical conditions may occur postnatally, such as Sheehan Syndrome.
## Psychological
Postnatal depression ("Baby blues") is very common, with approximately 50% of women suffering from it, potentially as early as 24 hours postpartum. It is usually limited in duration, lasting 36 to 48 hours. Apart from empathy and support from caregivers and family, treatment is not required. Approximately 10-20% of women will suffer the symptoms of major depression, and should be treated accordingly. Postpartum depression may be the response to the hormonal changes and life adjustment the woman goes through immediately after childbirth.
Postnatal Psychosis (also known as puerperal psychosis), is a more severe form of mental illness than postpartum depression.
Care provided by a Postpartum Doula will support the mother, assist with breastfeeding and baby care which enhances her confidence, helping to lessen her chances of developing postpartum depression or other postpartum mood disorders. | Postnatal
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Background
Postnatal (Latin for 'after birth') is the period beginning immediately after the birth of a child and extending for about six weeks. The period is also known as postpartum period and, less commonly, puerperium.
Biologically, it is the time after birth, a time in which the mother's body, including hormone levels and uterus size, return to prepregnancy conditions. Lochia is post-partum vaginal discharge, containing blood, mucus, and placental tissue.
During the first stages of this period, the newborn also starts his or her adaptation to extrauterine life, the most significant physiological transition until death.
In scientific literature the term is commonly abbreviated to PX. So that 'day P5' should be read as 'the fifth day after birth'.
# Woman care
A woman in the Western world who is delivering in a hospital may leave the hospital as early as 6 hours postpartum, though the average for spontaneous vaginal delivery (SVD) is 1-2 days, and the average caesarean section postnatal stay is 3-4 days.
During this time bleeding, bowel and bladder function, and baby care are monitored.
## Physical
The mother is assessed for tears, and is sutured if necessary. Also, she may suffer from constipation or hemorrhoids, both of which would be managed. The bladder is also assessed for infection, retention and any problems in the muscles.
The major focus of postpartum care is ensuring that the woman is healthy and capable of taking care of her newborn, equipped with all the information she needs about breastfeeding, reproductive health and contraception, and the imminent life adjustment.
Some medical conditions may occur postnatally, such as Sheehan Syndrome.
## Psychological
Postnatal depression ("Baby blues") is very common, with approximately 50% of women suffering from it, potentially as early as 24 hours postpartum. It is usually limited in duration, lasting 36 to 48 hours. Apart from empathy and support from caregivers and family, treatment is not required. Approximately 10-20% of women will suffer the symptoms of major depression, and should be treated accordingly. Postpartum depression may be the response to the hormonal changes and life adjustment the woman goes through immediately after childbirth.
Postnatal Psychosis (also known as puerperal psychosis), is a more severe form of mental illness than postpartum depression.
Care provided by a Postpartum Doula will support the mother, assist with breastfeeding and baby care which enhances her confidence, helping to lessen her chances of developing postpartum depression or other postpartum mood disorders. | https://www.wikidoc.org/index.php/Post-partum | |
bb25f2730cff11671b4a3a767f77dfdd2ad67236 | wikidoc | Pouchitis | Pouchitis
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Pouchitis is inflammation of the ileal pouch, which is created in the management of patients with ulcerative colitis, indeterminate colitis, or, rarely, other colitides.
Patients with pouchitis typically present with bloody diarrhea, urgency in passing stools, or discomfort while passing stools. Rarely, pain can occur with pouchitis.
Endoscopy in patients with pouchitis usually reveals erythematous pouch mucosa, loss of pseudocolonic vaculature or other architecture, and friability of the mucosa. Biopsies show evidence of inflammatory cells or red blood cells in the lamina propria.
Pouchitis is usually treated with antibiotics, and specifically usually with ciprofloxacin and metronidazole. In refractory cases, probiotics such as VSL-3 and Bio-K+ may be useful. | Pouchitis
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Pouchitis is inflammation of the ileal pouch, which is created in the management of patients with ulcerative colitis, indeterminate colitis, or, rarely, other colitides.[1][2]
Patients with pouchitis typically present with bloody diarrhea, urgency in passing stools, or discomfort while passing stools. Rarely, pain can occur with pouchitis.
Endoscopy in patients with pouchitis usually reveals erythematous pouch mucosa, loss of pseudocolonic vaculature or other architecture, and friability of the mucosa. Biopsies show evidence of inflammatory cells or red blood cells in the lamina propria.
Pouchitis is usually treated with antibiotics, and specifically usually with ciprofloxacin and metronidazole. In refractory cases, probiotics such as VSL-3 and Bio-K+ may be useful.[3] | https://www.wikidoc.org/index.php/Pouchitis | |
efe99d7f0bc3b1f207cda9ed500d6479e061a732 | wikidoc | Pox party | Pox party
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A pox party is a party held by parents for the purpose of infecting their children with childhood diseases, here chicken pox virus. Similar ideas have applied to other diseases eg Measles but are now strongly discouraged by doctors and health services. The reasoning behind this now largely historical practice is that guests are exposed to the varicella virus and contract the disease, developing strong and persistent immunity at an age before disaster is likely, from Chickenpox or Rubella particularly.
Since 1995 Chickenpox immunisation has been routine in the U.S. and parts of Canada, but not the UK. (See Chickenpox
Efficacy: The vaccine adequately immunises 70-90% of recipients, attenuating symptoms in those who do later contract the disease.
Children have a milder course of the disease than adults, for whom the disease can often be fatal. (See Chickenpox)
# Literary References
In The Astonishing Life of Octavian Nothing, Volume 1: The Pox Party by M.T. Anderson, the second part of the book describes a pox party outside of Boston in 1775, where all those previously uninfected by smallpox are inoculated by variolation, or by inserting pustules from former victims into a cut in the skin. Of the thirty-nine people so treated, three later die.
# Principal Complications of (Wild) Chickenpox
see also Chickenpox#complications
- Death or neurological damage: 0.002% of infected children.
- Shingles - a recrudescence of virus dormant in a nerve ganglion, with eruption in the distribution of that nerve, pain and commonly scarring. A proportion of people will retain the wild virus, of whom a proportion will develop shingles. The vaccine virus is not reported to do this. | Pox party
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
A pox party is a party held by parents for the purpose of infecting their children with childhood diseases, here chicken pox virus. Similar ideas have applied to other diseases eg Measles but are now strongly discouraged by doctors and health services. The reasoning behind this now largely historical practice is that guests are exposed to the varicella virus and contract the disease, developing strong and persistent immunity at an age before disaster is likely, from Chickenpox or Rubella particularly.
Since 1995 Chickenpox immunisation has been routine in the U.S. and parts of Canada, but not the UK. (See Chickenpox
Efficacy: The vaccine adequately immunises 70-90% of recipients, attenuating symptoms in those who do later contract the disease.
Children have a milder course of the disease than adults, for whom the disease can often be fatal. (See Chickenpox)
# Literary References
In The Astonishing Life of Octavian Nothing, Volume 1: The Pox Party by M.T. Anderson, the second part of the book describes a pox party outside of Boston in 1775, where all those previously uninfected by smallpox are inoculated by variolation, or by inserting pustules from former victims into a cut in the skin. Of the thirty-nine people so treated, three later die.
# Principal Complications of (Wild) Chickenpox
see also Chickenpox#complications
- Death or neurological damage: 0.002% of infected children.
- Shingles - a recrudescence of virus dormant in a nerve ganglion, with eruption in the distribution of that nerve, pain and commonly scarring. A proportion of people will retain the wild virus, of whom a proportion will develop shingles. The vaccine virus is not reported to do this.
# External links
- The return of the measles party
- Playing chicken: Some parents want children to catch chicken pox
Template:Vaccines
Template:SIB
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Pox_party | |
b2650eb0824df6ea8911ddc1b25b9961f484d465 | wikidoc | Practolol | Practolol
# Overview
Practolol (Eraldin, Dalzic, Praktol, Cardiol, Pralon, Cordialina, Eraldina, Teranol) is a selective beta blocker that has been used in the emergency treatment of cardiac arrhythmias. Practolol is no longer used as it is highly toxic despite the similarity of its chemical formula to propranolol. After its introduction, keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients. (British Medical Journal, March 15, 1975)
# Side Effects
Side effects are similar to those of other beta blockers, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia.
Furthermore, chronic use of practolol may cause oculomucocutaneous syndrome, a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes, otitis and sclerosing serositis. This syndrome has not been observed with other such beta blockers.
# Ban
This drug has been withdrawn from the market in India due to Oculomucocutaneous Syndrome. | Practolol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Practolol (Eraldin, Dalzic, Praktol, Cardiol, Pralon, Cordialina, Eraldina, Teranol) is a selective beta blocker that has been used in the emergency treatment of cardiac arrhythmias. Practolol is no longer used as it is highly toxic despite the similarity of its chemical formula to propranolol. After its introduction, keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients. (British Medical Journal, March 15, 1975)
# Side Effects
Side effects are similar to those of other beta blockers, such as bronchoconstriction, cardiac failure, cold extremities, fatigue and depression, hypoglycaemia.[1]
Furthermore, chronic use of practolol may cause oculomucocutaneous syndrome,[1] a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes, otitis and sclerosing serositis. This syndrome has not been observed with other such beta blockers.[2]
# Ban
This drug has been withdrawn from the market in India due to Oculomucocutaneous Syndrome.[3]
# External Links
- Guinea Pig study from 1975
- Liver effect study from 1981
- Study of uses during surgery
- Molecular structure
- Template:DiseasesDB | https://www.wikidoc.org/index.php/Practolol | |
84d5ef1d9fb6138b741e689602f89b8a3633984f | wikidoc | Pramoxine | Pramoxine
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Pramoxine is a local anesthetic that is FDA approved for the treatment of for the temporary relief of itching associated with minor skin irritations. Common adverse reactions include contact dermatitis, eczema.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- For the temporary relief of itching associated with minor skin irritations
- To open, squeeze cap tightly and turn pump counter-clockwise.
- Adults and children 2 years of age and older:
- apply to affected area not more than 3 to 4 times daily.
- Children under 2 years of age: consult a doctor.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pramoxine in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pramoxine in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Pramoxine in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pramoxine in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pramoxine in pediatric patients.
# Contraindications
There is limited information regarding Pramoxine Contraindications in the drug label.
# Warnings
- For external use only
- When using this product
- avoid contact with the eyes.
- Stop use and ask a doctor if
- condition worsens
- symptoms persist for more than 7 days or clear up and occur again within a few days.
- Caution -- Do not use in the eyes or nose. Not for prolonged use. Do not apply to large areas of the body. If redness, irritation, swelling, or pain persists or increases, discontinue use unless directed by a physician.
- Keep out of reach of children.
- If swallowed, get medical help or contact a Poison Control Center right away.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Pramoxine in the drug label.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Pramoxine in the drug label.
# Drug Interactions
There is limited information regarding Pramoxine Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
There is no FDA guidance on usage of Pramoxine in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pramoxine in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Pramoxine during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Pramoxine with respect to nursing mothers.
### Pediatric Use
There is no FDA guidance on the use of Pramoxine with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Pramoxine with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Pramoxine with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Pramoxine with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Pramoxine in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Pramoxine in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pramoxine in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Pramoxine in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Topical
### Monitoring
There is limited information regarding Monitoring of Pramoxine in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Pramoxine in the drug label.
# Overdosage
There is limited information regarding Chronic Overdose of Pramoxine in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Pramoxine Mechanism of Action in the drug label.
## Structure
There is limited information regarding Pramoxine Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Pramoxine in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Pramoxine in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Pramoxine in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Pramoxine in the drug label.
# How Supplied
There is limited information regarding Pramoxine How Supplied in the drug label.
## Storage
There is limited information regarding Pramoxine Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Pramoxine in the drug label.
# Precautions with Alcohol
- Alcohol-Pramoxine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Curasore
- Prax
- Proctofoam-NS
- Tronolane
- Sarna Sensitive
- Proctofoam
- PramoxGel
# Look-Alike Drug Names
There is limited information regarding Pramoxine Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Pramoxine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Pramoxine is a local anesthetic that is FDA approved for the treatment of for the temporary relief of itching associated with minor skin irritations. Common adverse reactions include contact dermatitis, eczema.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- For the temporary relief of itching associated with minor skin irritations
- To open, squeeze cap tightly and turn pump counter-clockwise.
- Adults and children 2 years of age and older:
- apply to affected area not more than 3 to 4 times daily.
- Children under 2 years of age: consult a doctor.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pramoxine in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pramoxine in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Pramoxine in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pramoxine in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pramoxine in pediatric patients.
# Contraindications
There is limited information regarding Pramoxine Contraindications in the drug label.
# Warnings
- For external use only
- When using this product
- avoid contact with the eyes.
- Stop use and ask a doctor if
- condition worsens
- symptoms persist for more than 7 days or clear up and occur again within a few days.
- Caution -- Do not use in the eyes or nose. Not for prolonged use. Do not apply to large areas of the body. If redness, irritation, swelling, or pain persists or increases, discontinue use unless directed by a physician.
- Keep out of reach of children.
- If swallowed, get medical help or contact a Poison Control Center right away.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Pramoxine in the drug label.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Pramoxine in the drug label.
# Drug Interactions
There is limited information regarding Pramoxine Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
There is no FDA guidance on usage of Pramoxine in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pramoxine in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Pramoxine during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Pramoxine with respect to nursing mothers.
### Pediatric Use
There is no FDA guidance on the use of Pramoxine with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Pramoxine with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Pramoxine with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Pramoxine with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Pramoxine in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Pramoxine in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pramoxine in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Pramoxine in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Topical
### Monitoring
There is limited information regarding Monitoring of Pramoxine in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Pramoxine in the drug label.
# Overdosage
There is limited information regarding Chronic Overdose of Pramoxine in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Pramoxine Mechanism of Action in the drug label.
## Structure
There is limited information regarding Pramoxine Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Pramoxine in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Pramoxine in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Pramoxine in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Pramoxine in the drug label.
# How Supplied
There is limited information regarding Pramoxine How Supplied in the drug label.
## Storage
There is limited information regarding Pramoxine Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Pramoxine in the drug label.
# Precautions with Alcohol
- Alcohol-Pramoxine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Curasore
- Prax
- Proctofoam-NS
- Tronolane
- Sarna Sensitive
- Proctofoam
- PramoxGel
# Look-Alike Drug Names
There is limited information regarding Pramoxine Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Pramoxine | |
d12f35db5698ebb32d80f8180afb6af9bd6779cd | wikidoc | Pre-labor | Pre-labor
# Overview
Pre-labor, also called "Prodromal Labor" is the early signs before labor starts. It is the body's preparation for real labour.
Prodromal Labor has been misnamed as “false-labor”. Prodromal labor begins much as traditional labor but does not progress to the birth of the baby. Not everyone feels this stage of labor, though it does always occur. However, this does not mean that every woman will experience every symptom. The term is used to describe a cluster of physical changes that may place in a pregnant woman before she goes into real labor, such as an increase in blood volume (sometimes resulting in oedema), braxton hicks contractions, the presence of colostrum in the breasts, and the dislodging of the mucous plug that has sealed the cervix during the pregnancy.
The term "false labor" is sometimes used to describe a cluster of Braxton Hicks contractions that are mistaken for real labor. | Pre-labor
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pre-labor, also called "Prodromal Labor" is the early signs before labor starts. It is the body's preparation for real labour.
Prodromal Labor has been misnamed as “false-labor”. Prodromal labor begins much as traditional labor but does not progress to the birth of the baby. Not everyone feels this stage of labor, though it does always occur. However, this does not mean that every woman will experience every symptom. The term is used to describe a cluster of physical changes that may place in a pregnant woman before she goes into real labor, such as an increase in blood volume (sometimes resulting in oedema), braxton hicks contractions, the presence of colostrum in the breasts, and the dislodging of the mucous plug that has sealed the cervix during the pregnancy.
The term "false labor" is sometimes used to describe a cluster of Braxton Hicks contractions that are mistaken for real labor.
Template:SIB
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Pre-labor | |
520a5db7082e0bfab32bf570a0a0510dcd5ebaa3 | wikidoc | Precocial | Precocial
In Biology, the term precocial refers to species in which the young are relatively mature and mobile from the moment of birth or hatching. The opposite developmental strategy is called "altricial", where the young are born helpless. Extremely precocial species may be called "superprecocial". These three categories form a continuum, without distinct gaps between them. Precocial species are normally nidifugous, meaning that they leave the nest shortly after birth.
The span between precocial and altricial species is particularly broad in birds. Precocial birds, including many ground-nesting species, have offspring that are born with well-ossified skeletons, with good sight, and covered with feathers. Very precocial birds can be ready to leave the nest in a short period of time following hatching (e.g. 24 hours). Many precocial chicks are not independent in thermoregulation (the ability to regulate their own body temperatures), and they depend on the attending parent(s) to brood them with body heat for a short period of time. Precocial birds find their own food, sometimes with help or instruction from the parents. Examples of precocial birds include the domestic chicken, many species of ducks and geese, and rails and crakes. The most extreme, superprecocial birds are the megapodes, where the newly-hatched chicks dig themselves out of the nest mound without parental assistance, and fly on the first day after hatching.
Precociality is also found in many other animal groups. Familiar examples of precocial mammals are most ungulates, the guinea pig, and most species of hare. This last example demonstrates that precociality is not a particularly conservative characteristic, in the evolutionary sense, since the closely related rabbit is highly altricial.
Precocial species typically have a longer gestation or incubation period than related altricial species, and smaller litters or clutches, since each offspring has to be brought to a relatively advanced (and large) state before birth or hatching.
The phenomenon of imprinting studied by Konrad Lorenz is characteristic of precocial birds.
# Etymology
The word "precocial" is derived from the same root as precocious, implying in both cases early maturity.
# Phylogeny
Precociality is thought to be ancestral in birds. Thus, altricial birds tend to be found in the most derived groups. There is some evidence for precociality in Protobirds (Elzanowski, 1995.) and Troodontids (Varricchio et al. 2002). | Precocial
In Biology, the term precocial refers to species in which the young are relatively mature and mobile from the moment of birth or hatching. The opposite developmental strategy is called "altricial", where the young are born helpless. Extremely precocial species may be called "superprecocial". These three categories form a continuum, without distinct gaps between them. Precocial species are normally nidifugous, meaning that they leave the nest shortly after birth.
The span between precocial and altricial species is particularly broad in birds. Precocial birds, including many ground-nesting species, have offspring that are born with well-ossified skeletons, with good sight, and covered with feathers. Very precocial birds can be ready to leave the nest in a short period of time following hatching (e.g. 24 hours). Many precocial chicks are not independent in thermoregulation (the ability to regulate their own body temperatures), and they depend on the attending parent(s) to brood them with body heat for a short period of time. Precocial birds find their own food, sometimes with help or instruction from the parents. Examples of precocial birds include the domestic chicken, many species of ducks and geese, and rails and crakes. The most extreme, superprecocial birds are the megapodes, where the newly-hatched chicks dig themselves out of the nest mound without parental assistance, and fly on the first day after hatching.
Precociality is also found in many other animal groups. Familiar examples of precocial mammals are most ungulates, the guinea pig, and most species of hare. This last example demonstrates that precociality is not a particularly conservative characteristic, in the evolutionary sense, since the closely related rabbit is highly altricial.
Precocial species typically have a longer gestation or incubation period than related altricial species, and smaller litters or clutches, since each offspring has to be brought to a relatively advanced (and large) state before birth or hatching.
The phenomenon of imprinting studied by Konrad Lorenz is characteristic of precocial birds.
# Etymology
The word "precocial" is derived from the same root as precocious, implying in both cases early maturity.[1]
# Phylogeny
Precociality is thought to be ancestral in birds. Thus, altricial birds tend to be found in the most derived groups. There is some evidence for precociality in Protobirds (Elzanowski, 1995.) and Troodontids (Varricchio et al. 2002). | https://www.wikidoc.org/index.php/Precocial | |
c047b6d0ecc553869ae188f36e6299a44dcac509 | wikidoc | Predation | Predation
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In ecology, predation describes a biological interaction where a predator organism feeds on another living organism or organisms known as prey. Predators may or may not kill their prey prior to feeding on them, but the act of predation always results in the (ecologically significant) death of the prey. The other main category of consumption is detritivory, the consumption of dead organic material (detritus). It can at times be difficult to separate the two feeding behaviors, for example where parasitic species prey on a host organism and then lay their eggs on it for their offspring to feed on its decaying corpse. The key characteristic of predation however is the predator's direct impact on the prey population. On the other hand, detritivores simply eat what is available and have no direct impact on the 'donor' organism(s).
# Classification of predators
The unifying theme in all classifications of predation is the predator lowering the fitness of its prey, or put another way, it reduces its prey's chances of survival, reproduction, or both. Ways of classifying predation surveyed here include grouping by trophic level or diet, by specialization, and by the nature of their interaction with prey.
## Functional classification
Classification of predators by the extent to which they feed on and interact with their prey is one way ecologists may wish to categorize the different types of predation. Instead of focusing on what they eat, this system classifies predators by the way in which they eat, and the general nature of the interaction between predator and prey species. Two factors are considered here: How close the predator and prey are physically (in the latter two cases the term prey may be replaced with host). Additionally, whether or not the prey are directly killed by the predator is considered, with the first and last cases involving certain death.
### True predation
A true predator is one which kills and eats another organism. Whereas other types of predator all harm their prey in some way, this form results in their instant death. Predators may hunt actively for prey, or sit and wait for prey to approach within striking distance, as in ambush predators. Some predators kill large prey and dismember or chew it prior to eating it, such as a jaguar, while others may eat their (usually much smaller) prey whole, as does a bottlenose dolphin or any snake. In some cases the prey organism may die in the mouth or digestive system of the predator. Baleen whales, for example, eat millions of microscopic plankton at once, the prey being broken down well after entering the whale. Seed predation is another form of true predation, as seeds represent potential organisms. Predators of this classification need not eat prey entirely, for example some predators cannot digest bones, while others can. Some may merely eat only part of an organism, as in grazing (see below), but still consistently cause its direct death.
### Grazing
Grazing organisms may also kill their prey species, but this is seldom the case. While some herbivores like zooplankton live on unicellular phytoplankton and have no choice but to kill their prey, many only eat a small part of the plant. Grazing livestock may pull some grass out at the roots, but most is simply grazed upon, allowing the plant to regrow once again. Kelp is frequently grazed in subtidal kelp forests, but regrows at the base of the blade continuously to cope with browsing pressure. Animals may also be 'grazed' upon; female mosquitos land on hosts briefly to gain sufficient proteins for the development of their offspring. Starfish may be grazed on, being capable of regenerating lost arms.
### Parasitism
Parasites can at times be difficult to distinguish from grazers. Their feeding behavior is similar in many ways, however they are noted for their close association with their host species. While a grazing species such as an elephant may travel many kilometers in a single day, grazing on many plants in the process, parasites form very close associations with their hosts, usually having only one or at most a few in their lifetime. This close living arrangement may be described by the term symbiosis, 'living together,' but unlike mutualism the association significantly reduces the fitness of the host. Parasitic organisms range from the macroscopic mistletoe, a parasitic plant, to microscopic internal parasites such as cholera. Some species however have more loose associations with their hosts. Lepidoptera (butterfly and moth) larvae may feed parasitically on only a single plant, or they may graze on several nearby plants. It is therefore wise to treat this classification system as a continuum rather than four isolated forms.
### Parasitoidism
Parasitoids are organisms living in or on their host and feeding directly upon it, eventually leading to its death. They are much like parasites in their close symbiotic relationship with their host or hosts. Like the previous two classifications parasitoid predators do not kill their hosts instantly. However, unlike parasites, they are very similar to true predators in that the fate of their prey is quite inevitably death. A well known example of a parasitoids are the ichneumon wasps, solitary insects living a free life as an adult, then laying eggs on or in another species such as a caterpillar. Its larva(e) feed on the growing host causing it little harm at first, but soon devouring the internal organs until finally destroying the nervous system resulting in prey death. By this stage the young wasp(s) are developed sufficiently to move to the next stage in their life cycle. Though limited mainly to the insect order Hymenoptera, parasitoids make up as much as 10% of all insect species.
## Degree of specialization
Among predators there is a large degree of specialization. Many predators specialize in hunting only one species of prey. Others are more opportunistic and will kill and eat almost anything (examples: humans, leopards, and dogs). The specialists are usually particularly well suited to capturing their preferred prey. The prey in turn, are often equally suited to escape that predator. This is called an evolutionary arms race and tends to keep the populations of both species in equilibrium. Some predators specialize in certain classes of prey, not just single species. Almost all will switch to other prey (with varying degrees of success) when the preferred target is extremely scarce, and they may also resort to scavenging or a herbivorous diet if possible.
## Trophic level
Predators are often another organism's prey, and likewise prey are often predators. Though blue jays prey on insects, they may in turn be prey for snakes, which may themselves be the prey of hawks. One way of classifying predators is by trophic level. Organisms which feed on autotrophs, the producers of the trophic pyramid, are known as herbivores or primary consumers; those that feed on heterotrophs such as animals are known as secondary consumers. Secondary consumers are a type of carnivore, but there are also tertiary consumers eating these carnivores, quartary consumers eating them, and so forth. Because only a fraction of energy is passed on to the next level, this hierarchy of predation must end somewhere, and very seldom goes higher than five or six levels. A predator at the top of any food chain (that is, one that is preyed upon by no organism) is called an apex predator; examples include the orca, tiger, and crocodile and even omnivorous humans. An apex predator in one environment may not retain this position if introduced to another habitat, such as dogs among crocodilians.
The problem with this system of classification is that many organisms eat from multiple levels of the food chain. A carnivore may eat both secondary and tertiary consumers, and its prey may itself be difficult to classify for similar reasons. Organisms showing both carnivory and herbivory are known as omnivores. Even supposedly strict herbivores may supplement their diet with meat. Carnivorous plants would be very difficult to fit into this classification, producing their own food but also digesting anything that they may trap. Organisms which eat detritivores would also be difficult to classify by such a scheme.
## Predation as competition
An alternative view offered by Richard Dawkins is of predation is a form of competition: the genes of both the predator and prey are competing for the body (or 'survival machine') of the prey organism. This is best understood in the context of the gene centered view of evolution.
# Ecological role
Predators may increase the biodiversity of communities by preventing a single species from becoming dominant. Such predators are known as keystone species, may have a profound influence on the balance of organisms in a particular ecosystem. Introduction or removal of this predator, or changes in its population density, can have drastic cascading effects on the equilibrium of many other populations in the ecosystem. For example, grazers of a grassland may prevent a single dominant species from taking over.
# Adaptations and behavior
The act of predation can be broken down into a maximum of four stages: Detection of prey, attack, capture and finally consumption. The relationship between predator and prey is one which is typically beneficial to the predator, and detrimental to the prey species. Sometimes, however, predation has indirect benefits to the prey species, though the individuals preyed upon themselves do not benefit. This means that, at each applicable stage, predator and prey species are in an evolutionary arms race maximize their respective abilities to obtain food or avoid being eaten. This interaction has resulted in a vast array of adaptations in both groups.
## General
One adaptation helping both predators and prey avoid detection is camouflage, a form of crypsis where species have an appearance which helps them blend into the background. Camouflage consists of not only color, but also shape and pattern. The background upon which the organism is seen can be both its environment (e.g. the praying mantis to the right resembling dead leaves) other organisms (e.g. zebras' stripes blend in with each other in a herd, making it difficult for lions to focus on a single target). The more convincing camouflage is, the more likely it is that the organism will go unseen.
Mimicry is a related phenomenon where an organism has a similar appearance to another species. One such example is the drone fly, which looks a lot like a bee, yet is completely harmless as it cannot sting at all. Another example of batesian mimicry is the io moth, (Automeris io), which has markings on its wings which resemble an owl's eyes. When an insectivorous predator disturbs the moth, it reveals its hind wings, temporarily startling the predator and giving it time to escape. Predators may also use mimicry to lure their prey, however. Female fireflies of the genus Photuris, for example, copy the light signals of other species, thereby attracting male fireflies which are then captured and eaten.
## Predator
While successful predation results in a gain of energy, hunting invariably involves energetic costs as well. When hunger is not an issue, most predators will generally not seek to attack prey since the costs outweigh the benefits. For instance, a large predatory fish like a shark that is well fed in an aquarium will typically ignore the smaller fish swimming around it (while the prey fish take advantage of the fact that the apex predator is apparently uninterested). Surplus killing represents a deviation from this type of behaviour. The treatment of consumption in terms of cost-benefit analysis is known as optimal foraging theory, and has been quite successful in the study of animal behavior. Costs and benefits are generally considered in energy gain per unit time, though other factors are also important, such as essential nutrients that have no caloric value but are necessary for survival and health.
Size-selective predation involves predators preferring prey of a certain size. Large prey may prove troublesome for a predator, while small prey might prove hard to find and in any case provide less of a reward. This has led to a correlation between the size of predators and their prey. Size may also act as a refuge for large prey, for example adult elephants are generally safe from predation by lions, but juveniles are vulnerable.
It has been observed that well-fed predator animals in a lax captivity (for instance, pet or farm animals) will usually differentiate between putative prey animals who are familiar co-inhabitants in the same human area from wild ones outside the area. This interaction can range from peaceful coexistence to close companionship; motivation to ignore the predatory instinct may result from mutual advantage or fear of reprisal from human masters who have made clear that harming co-inhabitants will not be tolerated. Pet cats and pet mice, for example, may live together in the same human residence without incident as companions. Pet cats and pet dogs under human mastership often depend on each other for warmth, companionship, and even protection, particularly in rural areas.
## Anti-predator adaptations
Antipredator adaptations have evolved in prey populations due to the selective pressures of predation over long periods of time.
### Mobbing behavior
Mobbing behavior occurs when a species turns the tables on their predator by cooperatively attacking or harassing it. This is most frequently seen in birds, though it is also known to occur in other social animals. For example, nesting gull colonies are widely seen to attack intruders, including humans. Costs of mobbing behavior include the risk of engaging with predators, as well as energy expended in the process; mockingbirds can effectively force a cat or dog to seek something less troublesome. One mockingbird might fly in front of the cat or dog, enticing it to lunge, while another pecks at the cat or dog from behind. While mobbing has evolved independently in many species, it only tends to be present in those whose young are frequently preyed on, especially birds. It may compliment cryptic behavior in the offspring themselves, such as camouflage and hiding. Mobbing calls may be made prior to or during engagement in harassment.
Mobbing behavior has functions beyond driving the predator away. Mobbing draws attention to the predator, making stealth attacks impossible. Mobbing also plays a critical role in the identification of predators and inter-generational learning about predator identification. Reintroduction of species is often unsuccessful because the established population lacks this cultural knowledge of how to identify local predators. Scientists are exploring ways to train populations to identify and respond to predators before releasing them into the wild.
Mobbing can be an interspecies activity: it is common for birds to respond to mobbing calls of a different species. Many birds will show up at the sight of mobbing and watch and call, but not participate. It should also be noted that some species can be on both ends of a mobbing attack; Crows are frequently mobbed by smaller songbirds, as they prey on eggs and young from these birds' nests, but these same crows will cooperate with smaller birds to drive away Hawks or larger mammalian predators. On occasion, birds will mob animals that pose no threat.
Black-headed Gulls are one species which aggressively engages intruding predators, such as Carrion Crows. Experiments on this species by Hans Kruuk involved placing hen eggs at intervals from a nesting colony, and recording the percentage of successful predation events as well as the probability of the crow being subjected to mobbing. The results showed decreasing mobbing with increased distance from the nest, which was correlated with increased predation success. Mobbing may function by reducing the predator's ability to locate nests, as predators cannot focus on locating eggs while they are under direct attack.
### Advertising unprofitability
Once a predator has detected its prey, one would expect it to pursue it. However, it is not always profitable for the predator to do so. Consider the example of a Thomson's Gazelle being spotted by a predator. Giving chase to prey requires a sacrifice in energy. If, however, there is some way the prey species can convey the information that it is unprofitable, energy will be saved by both organisms. Thomson's Gazelles are hunted by species such as lions and cheetahs. When they see the predator approach, they may start to run away, but then slow down and stot. Stotting describes a behavior involving jumping into the air with the legs kept straight and stiff, and the white rear fully visible. Obviously this behavior is maladaptive if they hope to outrun the predator, so it must serve some other purpose. Although other hypotheses have been put forward, evidence supports the proposition that they stot to signal an unprofitable chase. For example, cheetahs abandon more hunts when the gazelle stots, and in the event they do give chase, they are far less likely to make a kill.
Aposematism, where organisms are brightly colored as a warning to predators, is the antithesis of camouflage. Some organisms pose a threat to their predators - for example they may be poisonous, or able to harm them physically. Aposematic coloring involves bright, easily recognizable and unique colors and patterns. Upon being harmed (e.g. stung) by their prey, the appearance of such an organism will be remembered as something to avoid.
# Population dynamics
It is fairly clear that predators tend to lower the survival and fecundity of their prey, but on a higher level of organization, populations of predator and prey species also interact. It is obvious that predators depend on prey for survival, and this is reflected in predator populations being affected by changes in prey populations. It is not so obvious, however, that predators affect prey populations. Eating a prey organism may simply make room for another if the prey population is approaching its carrying capacity.
The population dynamics of predator-prey interactions can be modelled using the Lotka-Volterra equations. These provide a mathematical model for the cycling of predator and prey populations.
# Humans and predation
## In conservation
Predators are an important consideration in matters relating to conservation. Introduced predators may prove too much for populations which have not coevolved with them, leading to possible extinction. This will depend largely on how well the prey species can adapt to the new species, and whether or not the predator can turn to alternative food sources when prey populations fall to minimal levels. If a predator can use an alternative prey instead, it may shift its diet towards that species in a behavior known as functional response, while still eating the last remaining prey organisms. On the other hand the prey species may be able to survive if the predator has no alternative prey - in this case its population will necessarily crash following the decline in prey, allowing some small proportion of prey to survive. Introduction of an alternative prey may well lead to the extinction of prey, as this constraint is removed.
Predators are often the species endangered themselves. Competition for prey from other species could prove the end of a predator - if their ecological niche overlaps completely with that of another the competitive exclusion principle requires only one can survive. Loss of prey species may lead to coextinction of their predator. In addition, because predators are found in higher trophic levels, they are less abundant and much more vulnerable to extinction.
## Biological pest control
Predators may be put to use in conservation efforts to control introduced species. Although the aim in this situation is to remove the introduced species entirely, keeping its abundance down is often the only possibility. Predators from its natural range may be introduced to control populations, though in some cases this has little effect, and may even cause unforeseen problems. Besides their use in conservation biology, predators are also important for controlling pests in agriculture. Natural predators are an environmentally friendly and sustainable way of reducing damage to crops, and are one alternative to the use of chemical agents such as pesticides. | Predation
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
In ecology, predation describes a biological interaction where a predator organism feeds on another living organism or organisms known as prey.[1] Predators may or may not kill their prey prior to feeding on them, but the act of predation always results in the (ecologically significant) death of the prey[2]. The other main category of consumption is detritivory, the consumption of dead organic material (detritus). It can at times be difficult to separate the two feeding behaviors[1], for example where parasitic species prey on a host organism and then lay their eggs on it for their offspring to feed on its decaying corpse. The key characteristic of predation however is the predator's direct impact on the prey population. On the other hand, detritivores simply eat what is available and have no direct impact on the 'donor' organism(s).
# Classification of predators
The unifying theme in all classifications of predation is the predator lowering the fitness of its prey, or put another way, it reduces its prey's chances of survival, reproduction, or both. Ways of classifying predation surveyed here include grouping by trophic level or diet, by specialization, and by the nature of their interaction with prey.
## Functional classification
Classification of predators by the extent to which they feed on and interact with their prey is one way ecologists may wish to categorize the different types of predation. Instead of focusing on what they eat, this system classifies predators by the way in which they eat, and the general nature of the interaction between predator and prey species. Two factors are considered here: How close the predator and prey are physically (in the latter two cases the term prey may be replaced with host). Additionally, whether or not the prey are directly killed by the predator is considered, with the first and last cases involving certain death.
### True predation
A true predator is one which kills and eats another organism. Whereas other types of predator all harm their prey in some way, this form results in their instant death. Predators may hunt actively for prey, or sit and wait for prey to approach within striking distance, as in ambush predators. Some predators kill large prey and dismember or chew it prior to eating it, such as a jaguar, while others may eat their (usually much smaller) prey whole, as does a bottlenose dolphin or any snake. In some cases the prey organism may die in the mouth or digestive system of the predator. Baleen whales, for example, eat millions of microscopic plankton at once, the prey being broken down well after entering the whale. Seed predation is another form of true predation, as seeds represent potential organisms. Predators of this classification need not eat prey entirely, for example some predators cannot digest bones, while others can. Some may merely eat only part of an organism, as in grazing (see below), but still consistently cause its direct death.
### Grazing
Grazing organisms may also kill their prey species, but this is seldom the case. While some herbivores like zooplankton live on unicellular phytoplankton and have no choice but to kill their prey, many only eat a small part of the plant. Grazing livestock may pull some grass out at the roots, but most is simply grazed upon, allowing the plant to regrow once again. Kelp is frequently grazed in subtidal kelp forests, but regrows at the base of the blade continuously to cope with browsing pressure. Animals may also be 'grazed' upon; female mosquitos land on hosts briefly to gain sufficient proteins for the development of their offspring. Starfish may be grazed on, being capable of regenerating lost arms.
### Parasitism
Parasites can at times be difficult to distinguish from grazers. Their feeding behavior is similar in many ways, however they are noted for their close association with their host species. While a grazing species such as an elephant may travel many kilometers in a single day, grazing on many plants in the process, parasites form very close associations with their hosts, usually having only one or at most a few in their lifetime. This close living arrangement may be described by the term symbiosis, 'living together,' but unlike mutualism the association significantly reduces the fitness of the host. Parasitic organisms range from the macroscopic mistletoe, a parasitic plant, to microscopic internal parasites such as cholera. Some species however have more loose associations with their hosts. Lepidoptera (butterfly and moth) larvae may feed parasitically on only a single plant, or they may graze on several nearby plants. It is therefore wise to treat this classification system as a continuum rather than four isolated forms.
### Parasitoidism
Parasitoids are organisms living in or on their host and feeding directly upon it, eventually leading to its death. They are much like parasites in their close symbiotic relationship with their host or hosts. Like the previous two classifications parasitoid predators do not kill their hosts instantly. However, unlike parasites, they are very similar to true predators in that the fate of their prey is quite inevitably death. A well known example of a parasitoids are the ichneumon wasps, solitary insects living a free life as an adult, then laying eggs on or in another species such as a caterpillar. Its larva(e) feed on the growing host causing it little harm at first, but soon devouring the internal organs until finally destroying the nervous system resulting in prey death. By this stage the young wasp(s) are developed sufficiently to move to the next stage in their life cycle. Though limited mainly to the insect order Hymenoptera, parasitoids make up as much as 10% of all insect species.[3]
## Degree of specialization
Among predators there is a large degree of specialization. Many predators specialize in hunting only one species of prey. Others are more opportunistic and will kill and eat almost anything (examples: humans, leopards, and dogs). The specialists are usually particularly well suited to capturing their preferred prey. The prey in turn, are often equally suited to escape that predator. This is called an evolutionary arms race and tends to keep the populations of both species in equilibrium. Some predators specialize in certain classes of prey, not just single species. Almost all will switch to other prey (with varying degrees of success) when the preferred target is extremely scarce, and they may also resort to scavenging or a herbivorous diet if possible.[4]
## Trophic level
Predators are often another organism's prey, and likewise prey are often predators. Though blue jays prey on insects, they may in turn be prey for snakes, which may themselves be the prey of hawks. One way of classifying predators is by trophic level. Organisms which feed on autotrophs, the producers of the trophic pyramid, are known as herbivores or primary consumers; those that feed on heterotrophs such as animals are known as secondary consumers. Secondary consumers are a type of carnivore, but there are also tertiary consumers eating these carnivores, quartary consumers eating them, and so forth. Because only a fraction of energy is passed on to the next level, this hierarchy of predation must end somewhere, and very seldom goes higher than five or six levels. A predator at the top of any food chain (that is, one that is preyed upon by no organism) is called an apex predator; examples include the orca, tiger, and crocodile and even omnivorous humans. An apex predator in one environment may not retain this position if introduced to another habitat, such as dogs among crocodilians.
The problem with this system of classification is that many organisms eat from multiple levels of the food chain. A carnivore may eat both secondary and tertiary consumers, and its prey may itself be difficult to classify for similar reasons. Organisms showing both carnivory and herbivory are known as omnivores. Even supposedly strict herbivores may supplement their diet with meat. Carnivorous plants would be very difficult to fit into this classification, producing their own food but also digesting anything that they may trap. Organisms which eat detritivores would also be difficult to classify by such a scheme.
## Predation as competition
An alternative view offered by Richard Dawkins is of predation is a form of competition: the genes of both the predator and prey are competing for the body (or 'survival machine') of the prey organism.[5] This is best understood in the context of the gene centered view of evolution.
# Ecological role
Predators may increase the biodiversity of communities by preventing a single species from becoming dominant. Such predators are known as keystone species, may have a profound influence on the balance of organisms in a particular ecosystem. Introduction or removal of this predator, or changes in its population density, can have drastic cascading effects on the equilibrium of many other populations in the ecosystem. For example, grazers of a grassland may prevent a single dominant species from taking over.[6]
# Adaptations and behavior
The act of predation can be broken down into a maximum of four stages: Detection of prey, attack, capture and finally consumption.[7] The relationship between predator and prey is one which is typically beneficial to the predator, and detrimental to the prey species. Sometimes, however, predation has indirect benefits to the prey species,[8] though the individuals preyed upon themselves do not benefit.[9] This means that, at each applicable stage, predator and prey species are in an evolutionary arms race maximize their respective abilities to obtain food or avoid being eaten. This interaction has resulted in a vast array of adaptations in both groups.
## General
One adaptation helping both predators and prey avoid detection is camouflage, a form of crypsis where species have an appearance which helps them blend into the background. Camouflage consists of not only color, but also shape and pattern. The background upon which the organism is seen can be both its environment (e.g. the praying mantis to the right resembling dead leaves) other organisms (e.g. zebras' stripes blend in with each other in a herd, making it difficult for lions to focus on a single target). The more convincing camouflage is, the more likely it is that the organism will go unseen.
Mimicry is a related phenomenon where an organism has a similar appearance to another species. One such example is the drone fly, which looks a lot like a bee, yet is completely harmless as it cannot sting at all. Another example of batesian mimicry is the io moth, (Automeris io), which has markings on its wings which resemble an owl's eyes. When an insectivorous predator disturbs the moth, it reveals its hind wings, temporarily startling the predator and giving it time to escape. Predators may also use mimicry to lure their prey, however. Female fireflies of the genus Photuris, for example, copy the light signals of other species, thereby attracting male fireflies which are then captured and eaten.[10]
## Predator
While successful predation results in a gain of energy, hunting invariably involves energetic costs as well. When hunger is not an issue, most predators will generally not seek to attack prey since the costs outweigh the benefits. For instance, a large predatory fish like a shark that is well fed in an aquarium will typically ignore the smaller fish swimming around it (while the prey fish take advantage of the fact that the apex predator is apparently uninterested). Surplus killing represents a deviation from this type of behaviour. The treatment of consumption in terms of cost-benefit analysis is known as optimal foraging theory, and has been quite successful in the study of animal behavior. Costs and benefits are generally considered in energy gain per unit time, though other factors are also important, such as essential nutrients that have no caloric value but are necessary for survival and health.
Size-selective predation involves predators preferring prey of a certain size. Large prey may prove troublesome for a predator, while small prey might prove hard to find and in any case provide less of a reward. This has led to a correlation between the size of predators and their prey.[11] Size may also act as a refuge for large prey, for example adult elephants are generally safe from predation by lions, but juveniles are vulnerable.[11]
It has been observed that well-fed predator animals in a lax captivity (for instance, pet or farm animals) will usually differentiate between putative prey animals who are familiar co-inhabitants in the same human area from wild ones outside the area. This interaction can range from peaceful coexistence to close companionship; motivation to ignore the predatory instinct may result from mutual advantage or fear of reprisal from human masters who have made clear that harming co-inhabitants will not be tolerated. Pet cats and pet mice, for example, may live together in the same human residence without incident as companions. Pet cats and pet dogs under human mastership often depend on each other for warmth, companionship, and even protection, particularly in rural areas.
## Anti-predator adaptations
Antipredator adaptations have evolved in prey populations due to the selective pressures of predation over long periods of time.
### Mobbing behavior
Mobbing behavior occurs when a species turns the tables on their predator by cooperatively attacking or harassing it. This is most frequently seen in birds, though it is also known to occur in other social animals. For example, nesting gull colonies are widely seen to attack intruders, including humans. Costs of mobbing behavior include the risk of engaging with predators, as well as energy expended in the process; mockingbirds can effectively force a cat or dog to seek something less troublesome. One mockingbird might fly in front of the cat or dog, enticing it to lunge, while another pecks at the cat or dog from behind. While mobbing has evolved independently in many species, it only tends to be present in those whose young are frequently preyed on, especially birds. It may compliment cryptic behavior in the offspring themselves, such as camouflage and hiding. Mobbing calls may be made prior to or during engagement in harassment.
Mobbing behavior has functions beyond driving the predator away. Mobbing draws attention to the predator, making stealth attacks impossible. Mobbing also plays a critical role in the identification of predators and inter-generational learning about predator identification. Reintroduction of species is often unsuccessful because the established population lacks this cultural knowledge of how to identify local predators. Scientists are exploring ways to train populations to identify and respond to predators before releasing them into the wild. [12]
Mobbing can be an interspecies activity: it is common for birds to respond to mobbing calls of a different species. Many birds will show up at the sight of mobbing and watch and call, but not participate. It should also be noted that some species can be on both ends of a mobbing attack; Crows are frequently mobbed by smaller songbirds, as they prey on eggs and young from these birds' nests, but these same crows will cooperate with smaller birds to drive away Hawks or larger mammalian predators. On occasion, birds will mob animals that pose no threat.
Black-headed Gulls are one species which aggressively engages intruding predators, such as Carrion Crows. Experiments on this species by Hans Kruuk involved placing hen eggs at intervals from a nesting colony, and recording the percentage of successful predation events as well as the probability of the crow being subjected to mobbing.[13] The results showed decreasing mobbing with increased distance from the nest, which was correlated with increased predation success. Mobbing may function by reducing the predator's ability to locate nests, as predators cannot focus on locating eggs while they are under direct attack.
### Advertising unprofitability
Once a predator has detected its prey, one would expect it to pursue it. However, it is not always profitable for the predator to do so. Consider the example of a Thomson's Gazelle being spotted by a predator. Giving chase to prey requires a sacrifice in energy. If, however, there is some way the prey species can convey the information that it is unprofitable, energy will be saved by both organisms. Thomson's Gazelles are hunted by species such as lions and cheetahs. When they see the predator approach, they may start to run away, but then slow down and stot. Stotting describes a behavior involving jumping into the air with the legs kept straight and stiff, and the white rear fully visible. Obviously this behavior is maladaptive if they hope to outrun the predator, so it must serve some other purpose. Although other hypotheses have been put forward, evidence supports the proposition that they stot to signal an unprofitable chase. For example, cheetahs abandon more hunts when the gazelle stots, and in the event they do give chase, they are far less likely to make a kill.[14]
Aposematism, where organisms are brightly colored as a warning to predators, is the antithesis of camouflage. Some organisms pose a threat to their predators - for example they may be poisonous, or able to harm them physically. Aposematic coloring involves bright, easily recognizable and unique colors and patterns. Upon being harmed (e.g. stung) by their prey, the appearance of such an organism will be remembered as something to avoid.
# Population dynamics
It is fairly clear that predators tend to lower the survival and fecundity of their prey, but on a higher level of organization, populations of predator and prey species also interact. It is obvious that predators depend on prey for survival, and this is reflected in predator populations being affected by changes in prey populations. It is not so obvious, however, that predators affect prey populations. Eating a prey organism may simply make room for another if the prey population is approaching its carrying capacity.
The population dynamics of predator-prey interactions can be modelled using the Lotka-Volterra equations. These provide a mathematical model for the cycling of predator and prey populations.
# Humans and predation
## In conservation
Predators are an important consideration in matters relating to conservation. Introduced predators may prove too much for populations which have not coevolved with them, leading to possible extinction. This will depend largely on how well the prey species can adapt to the new species, and whether or not the predator can turn to alternative food sources when prey populations fall to minimal levels. If a predator can use an alternative prey instead, it may shift its diet towards that species in a behavior known as functional response, while still eating the last remaining prey organisms. On the other hand the prey species may be able to survive if the predator has no alternative prey - in this case its population will necessarily crash following the decline in prey, allowing some small proportion of prey to survive. Introduction of an alternative prey may well lead to the extinction of prey, as this constraint is removed.
Predators are often the species endangered themselves. Competition for prey from other species could prove the end of a predator - if their ecological niche overlaps completely with that of another the competitive exclusion principle requires only one can survive. Loss of prey species may lead to coextinction of their predator. In addition, because predators are found in higher trophic levels, they are less abundant and much more vulnerable to extinction.
## Biological pest control
Predators may be put to use in conservation efforts to control introduced species. Although the aim in this situation is to remove the introduced species entirely, keeping its abundance down is often the only possibility. Predators from its natural range may be introduced to control populations, though in some cases this has little effect, and may even cause unforeseen problems. Besides their use in conservation biology, predators are also important for controlling pests in agriculture. Natural predators are an environmentally friendly and sustainable way of reducing damage to crops, and are one alternative to the use of chemical agents such as pesticides. | https://www.wikidoc.org/index.php/Predation | |
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Prepodyne is an iodophoric surgical scrub soap usually consisting of a povidone-iodine and detergent solution. It is used for antisepsis of the hands and forearms prior to performing surgery.
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26d2bb7307383c07061d3a15c67c868e91e3256a | wikidoc | Primidone | Primidone
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Primidone is an anticonvulsant that is FDA approved for the treatment of epilepsy. Common adverse reactions include ataxia, vertigo.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Epilepsy, Adjunct or monotherapy
- Primidone tablets, USP, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.
- Dosing Information
- The usual oral primidone maintenance dose for adults is 250 milligrams 3 or 4 times daily. When initiating primidone therapy, the drug should be started at 100 to 125 milligrams at bedtime for 3 days, 100 to 125 milligrams twice daily for days 4 to 6, 100 to 125 milligrams 3 times daily for days 7 to 9, and finally a maintenance dose of 250 milligrams 3 times daily.
- Primidone doses greater than 2 grams/day are not recommended.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Primidone in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Primidone in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- CHILDREN UNDER 8 YEARS:
- To start primidone therapy in children under 8 years of age, 50 milligrams can be given at bedtime for the first three days. For days 4 through 6, the dose is 50 milligrams twice a day. For days 7 through 9, the dose is 100 milligrams twice a day. The dose from day 10 until maintenance is reached is 125 milligrams to 250 milligrams three times a day, or 10 to 25 milligrams/kilogram/day in divided doses.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
- CHILDREN OVER 8 YEARS:
- The usual oral primidone maintenance dose for children 8 years of age and older is 250 milligrams 3 or 4 times daily. When initiating primidone therapy, the drug should be started at 100 to 125 milligrams at bedtime for 3 days, 100 to 125 milligrams twice daily for days 4 to 6, 100 to 125 milligrams 3 times daily for days 7 to 9, and finally a maintenance dose of 250 milligrams 3 times daily.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
- WITHDRAWAL SCHEDULE:
- Withdrawal of anticonvulsant medication in children free of seizures for 2 to 4 years appears to be safe, with the majority of children remaining free of seizures after medication withdrawal. In a prospective study, anticonvulsant medications were discontinued in 88 epileptic children who had not had a seizure for 2 to 4 years. Anticonvulsants were withdrawn gradually over 2 to 3 months. The type of seizure, age at onset and EEG characteristics were considered important in predicting the outcome of anticonvulsant withdrawal. The EEG obtained prior to withdrawal of the anticonvulsant was a useful predictor, with a normal EEG associated with good outcome. A poor outcome was associated with specific abnormalities such as slowing, spikes, and focality. A favorable prognosis was also demonstrated for patients with a history of complex partial seizures that had been controlled for two years on medication. Patients with a history of atypical febrile seizures had a poor prognosis. A better prognosis was observed in patients with a younger age at the onset of seizure activity; however, this was only significant if EEG slowing was present. These data indicate that withdrawal of anticonvulsants in children who have been seizure free for 2 years is relatively safe, and it is possible to predict outcome reasonably well on the basis of EEG, type of seizure and age of onset of seizures.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Primidone in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Primidone in pediatric patients.
# Contraindications
- Primidone, USP is contraindicated in:
- patients with porphyria and
- who are hypersensitive to phenobarbital.
# Warnings
- The abrupt withdrawal of antiepileptic medication may precipitate status epilepticus. The therapeutic efficacy of a dosage regimen takes several weeks before it can be assessed.
- Suicidal Behavior and Ideation
- Antiepileptic drugs (AEDs), including Primidone, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
- The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
- The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.
- The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
- Anyone considering prescribing primidone or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
- Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
- Usage in Pregnancy
- To provide information regarding the effects of in utero exposure to primidone, physicians are advised to recommend that pregnant patients taking Primidone enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website
- The effects of primidone in human pregnancy and nursing infants are unknown.
- Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.
- The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause-and-effect relationship.
- There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans, the possibility also exists that other factors leading to birth defects, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorders are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
- The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. Pregnant women under anticonvulsant therapy should receive prophylactic vitamin K1 therapy for one month prior to, and during, delivery.
### Precautions
- The total daily dosage should not exceed 2 g. Since primidone therapy generally extends over prolonged periods, a complete blood count and a sequential multiple analysis-12 (SMA-12) test should be made every six months.
- In Nursing Mothers
- There is evidence that in mothers treated with primidone, the drug appears in the milk in substantial quantities. Since tests for the presence of primidone in biological fluids are too complex to be carried out in the average clinical laboratory, it is suggested that the presence of undue somnolence and drowsiness in nursing newborns of primidone-treated mothers be taken as an indication that nursing should be discontinued.
# Adverse Reactions
## Clinical Trials Experience
- The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions. Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistent or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to primidone and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.
## Postmarketing Experience
- There is limited information regarding Postmarketing Experience of Primidone in the drug label.
# Drug Interactions
There is limited information regarding Primidone Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
- There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Primidone in women who are pregnant.
### Labor and Delivery
- There is no FDA guidance on use of Primidone during labor and delivery.
### Nursing Mothers
- There is no FDA guidance on the use of Primidone with respect to nursing mothers.
### Pediatric Use
- There is no FDA guidance on the use of Primidone with respect to pediatric patients.
### Geriatic Use
- There is no FDA guidance on the use of Primidone with respect to geriatric patients.
### Gender
- There is no FDA guidance on the use of Primidone with respect to specific gender populations.
### Race
- There is no FDA guidance on the use of Primidone with respect to specific racial populations.
### Renal Impairment
- There is no FDA guidance on the use of Primidone in patients with renal impairment.
### Hepatic Impairment
- There is no FDA guidance on the use of Primidone in patients with hepatic impairment.
### Females of Reproductive Potential and Males
- There is no FDA guidance on the use of Primidone in women of reproductive potentials and males.
### Immunocompromised Patients
- There is no FDA guidance one the use of Primidone in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Adult Dosage
- Patients 8 years of age and older who have received no previous treatment may be started on primidone according to the following regimen using either 50 mg or scored 250 mg primidone tablets, USP:
- Days 1 to 3: 100 to 125 mg at bedtime.
- Days 4 to 6: 100 to 125 mg b.i.d.
- Days 7 to 9: 100 to 125 mg t.i.d.
- Day 10 to maintenance: 250 mg t.i.d.
- For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg primidone tablets, USP daily in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.
- Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone, USP may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone, USP is between 5 to 12 mcg/mL.
- In Patients Already Receiving Other Anticonvulsants
- Primidone tablets, USP should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with primidone tablets, USP alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.
- Pediatric Dosage
- For children under 8 years of age, the following regimen may be used:
- Days 1 to 3: 50 mg at bedtime.
- Days 4 to 6: 50 mg b.i.d.
- Days 7 to 9: 100 mg b.i.d.
- Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.
- For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or 10 to 25 mg/kg/day in divided doses.
### Monitoring
- There is limited information regarding Monitoring of Primidone in the drug label.
# IV Compatibility
- There is limited information regarding IV Compatibility of Primidone in the drug label.
# Overdosage
- There is limited information regarding Chronic Overdose of Primidone in the drug label.
# Pharmacology
## Mechanism of Action
## Structure
- Primidone, USP is a white, crystalline, highly stable substance, M.P. 279-284° C. It is poorly soluble in water (60 mg per 100 mL at 37° C) and in most organic solvents. It possesses no acidic properties, in contrast to its barbiturate analog.
- Chemical name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H)-pyrimidinedione. Structural formula:
- Primidone tablets, USP 50 mg and 250 mg tablets contain the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, methyl cellulose, microcrystalline cellulose, sodium lauryl sulfate, sodium starch glycolate.
## Pharmacodynamics
- There is limited information regarding Pharmacodynamics of Primidone in the drug label.
## Pharmacokinetics
- There is limited information regarding Pharmacokinetics of Primidone in the drug label.
## Nonclinical Toxicology
- There is limited information regarding Nonclinical Toxicology of Primidone in the drug label.
# Clinical Studies
- There is limited information regarding Clinical Studies of Primidone in the drug label.
# How Supplied
- Primidone Tablets USP 50 mg are supplied as white, round, flat faced tablets, debossed
- AN above 44 on one side and cut-bisected on the other side.
- NDC 50268-686-15 10 Tablets per card, 5 cards per carton
- Primidone Tablets USP 250 mg are supplied as white, round, flat faced tablets, debossed
- AN bisect 545 on one side and plain on the other side.
- NDC 50268-687-15 10 Tablets per card, 5 cards per carton
## Storage
- Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
- KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN.
- Dispensed in a blister punch material for Institutional Use Only.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Information for Patients
- Suicidal Thinking and Behavior - Patients, their caregivers, and families should be counseled that AEDs, including Mysoline, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
- Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see Usage in Pregnancy section).
- Please refer to the Primidone Medication Guide for more information.
# Precautions with Alcohol
- Alcohol-Primidone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Mysoline
# Look-Alike Drug Names
- A® — B®
# Drug Shortage Status
# Price | Primidone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Primidone is an anticonvulsant that is FDA approved for the treatment of epilepsy. Common adverse reactions include ataxia, vertigo.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Epilepsy, Adjunct or monotherapy
- Primidone tablets, USP, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.
- Dosing Information
- The usual oral primidone maintenance dose for adults is 250 milligrams 3 or 4 times daily. When initiating primidone therapy, the drug should be started at 100 to 125 milligrams at bedtime for 3 days, 100 to 125 milligrams twice daily for days 4 to 6, 100 to 125 milligrams 3 times daily for days 7 to 9, and finally a maintenance dose of 250 milligrams 3 times daily.
- Primidone doses greater than 2 grams/day are not recommended.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Primidone in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Primidone in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- CHILDREN UNDER 8 YEARS:
- To start primidone therapy in children under 8 years of age, 50 milligrams can be given at bedtime for the first three days. For days 4 through 6, the dose is 50 milligrams twice a day. For days 7 through 9, the dose is 100 milligrams twice a day. The dose from day 10 until maintenance is reached is 125 milligrams to 250 milligrams three times a day, or 10 to 25 milligrams/kilogram/day in divided doses.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
- CHILDREN OVER 8 YEARS:
- The usual oral primidone maintenance dose for children 8 years of age and older is 250 milligrams 3 or 4 times daily. When initiating primidone therapy, the drug should be started at 100 to 125 milligrams at bedtime for 3 days, 100 to 125 milligrams twice daily for days 4 to 6, 100 to 125 milligrams 3 times daily for days 7 to 9, and finally a maintenance dose of 250 milligrams 3 times daily.
- When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while the dosage of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks.
- WITHDRAWAL SCHEDULE:
- Withdrawal of anticonvulsant medication in children free of seizures for 2 to 4 years appears to be safe, with the majority of children remaining free of seizures after medication withdrawal. In a prospective study, anticonvulsant medications were discontinued in 88 epileptic children who had not had a seizure for 2 to 4 years. Anticonvulsants were withdrawn gradually over 2 to 3 months. The type of seizure, age at onset and EEG characteristics were considered important in predicting the outcome of anticonvulsant withdrawal. The EEG obtained prior to withdrawal of the anticonvulsant was a useful predictor, with a normal EEG associated with good outcome. A poor outcome was associated with specific abnormalities such as slowing, spikes, and focality. A favorable prognosis was also demonstrated for patients with a history of complex partial seizures that had been controlled for two years on medication. Patients with a history of atypical febrile seizures had a poor prognosis. A better prognosis was observed in patients with a younger age at the onset of seizure activity; however, this was only significant if EEG slowing was present. These data indicate that withdrawal of anticonvulsants in children who have been seizure free for 2 years is relatively safe, and it is possible to predict outcome reasonably well on the basis of EEG, type of seizure and age of onset of seizures.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Primidone in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Primidone in pediatric patients.
# Contraindications
- Primidone, USP is contraindicated in:
- patients with porphyria and
- who are hypersensitive to phenobarbital.
# Warnings
- The abrupt withdrawal of antiepileptic medication may precipitate status epilepticus. The therapeutic efficacy of a dosage regimen takes several weeks before it can be assessed.
- Suicidal Behavior and Ideation
- Antiepileptic drugs (AEDs), including Primidone, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
- The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
- The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.
- The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
- Anyone considering prescribing primidone or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
- Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
- Usage in Pregnancy
- To provide information regarding the effects of in utero exposure to primidone, physicians are advised to recommend that pregnant patients taking Primidone enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website
- http://www.aedpregnancyregistry.org/.
- The effects of primidone in human pregnancy and nursing infants are unknown.
- Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.
- The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause-and-effect relationship.
- There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans, the possibility also exists that other factors leading to birth defects, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorders are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
- The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. Pregnant women under anticonvulsant therapy should receive prophylactic vitamin K1 therapy for one month prior to, and during, delivery.
### Precautions
- The total daily dosage should not exceed 2 g. Since primidone therapy generally extends over prolonged periods, a complete blood count and a sequential multiple analysis-12 (SMA-12) test should be made every six months.
- In Nursing Mothers
- There is evidence that in mothers treated with primidone, the drug appears in the milk in substantial quantities. Since tests for the presence of primidone in biological fluids are too complex to be carried out in the average clinical laboratory, it is suggested that the presence of undue somnolence and drowsiness in nursing newborns of primidone-treated mothers be taken as an indication that nursing should be discontinued.
# Adverse Reactions
## Clinical Trials Experience
- The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions. Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistent or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to primidone and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.
## Postmarketing Experience
- There is limited information regarding Postmarketing Experience of Primidone in the drug label.
# Drug Interactions
There is limited information regarding Primidone Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
- There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Primidone in women who are pregnant.
### Labor and Delivery
- There is no FDA guidance on use of Primidone during labor and delivery.
### Nursing Mothers
- There is no FDA guidance on the use of Primidone with respect to nursing mothers.
### Pediatric Use
- There is no FDA guidance on the use of Primidone with respect to pediatric patients.
### Geriatic Use
- There is no FDA guidance on the use of Primidone with respect to geriatric patients.
### Gender
- There is no FDA guidance on the use of Primidone with respect to specific gender populations.
### Race
- There is no FDA guidance on the use of Primidone with respect to specific racial populations.
### Renal Impairment
- There is no FDA guidance on the use of Primidone in patients with renal impairment.
### Hepatic Impairment
- There is no FDA guidance on the use of Primidone in patients with hepatic impairment.
### Females of Reproductive Potential and Males
- There is no FDA guidance on the use of Primidone in women of reproductive potentials and males.
### Immunocompromised Patients
- There is no FDA guidance one the use of Primidone in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Adult Dosage
- Patients 8 years of age and older who have received no previous treatment may be started on primidone according to the following regimen using either 50 mg or scored 250 mg primidone tablets, USP:
- Days 1 to 3: 100 to 125 mg at bedtime.
- Days 4 to 6: 100 to 125 mg b.i.d.
- Days 7 to 9: 100 to 125 mg t.i.d.
- Day 10 to maintenance: 250 mg t.i.d.
- For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg primidone tablets, USP daily in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.
- Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone, USP may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone, USP is between 5 to 12 mcg/mL.
- In Patients Already Receiving Other Anticonvulsants
- Primidone tablets, USP should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with primidone tablets, USP alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.
- Pediatric Dosage
- For children under 8 years of age, the following regimen may be used:
- Days 1 to 3: 50 mg at bedtime.
- Days 4 to 6: 50 mg b.i.d.
- Days 7 to 9: 100 mg b.i.d.
- Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.
- For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or 10 to 25 mg/kg/day in divided doses.
### Monitoring
- There is limited information regarding Monitoring of Primidone in the drug label.
# IV Compatibility
- There is limited information regarding IV Compatibility of Primidone in the drug label.
# Overdosage
- There is limited information regarding Chronic Overdose of Primidone in the drug label.
# Pharmacology
## Mechanism of Action
-
## Structure
- Primidone, USP is a white, crystalline, highly stable substance, M.P. 279-284° C. It is poorly soluble in water (60 mg per 100 mL at 37° C) and in most organic solvents. It possesses no acidic properties, in contrast to its barbiturate analog.
- Chemical name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H)-pyrimidinedione. Structural formula:
- Primidone tablets, USP 50 mg and 250 mg tablets contain the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, methyl cellulose, microcrystalline cellulose, sodium lauryl sulfate, sodium starch glycolate.
## Pharmacodynamics
- There is limited information regarding Pharmacodynamics of Primidone in the drug label.
## Pharmacokinetics
- There is limited information regarding Pharmacokinetics of Primidone in the drug label.
## Nonclinical Toxicology
- There is limited information regarding Nonclinical Toxicology of Primidone in the drug label.
# Clinical Studies
- There is limited information regarding Clinical Studies of Primidone in the drug label.
# How Supplied
- Primidone Tablets USP 50 mg are supplied as white, round, flat faced tablets, debossed
- AN above 44 on one side and cut-bisected on the other side.
- NDC 50268-686-15 10 Tablets per card, 5 cards per carton
- Primidone Tablets USP 250 mg are supplied as white, round, flat faced tablets, debossed
- AN bisect 545 on one side and plain on the other side.
- NDC 50268-687-15 10 Tablets per card, 5 cards per carton
## Storage
- Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
- [See USP Controlled Room Temperature].
- KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN.
- Dispensed in a blister punch material for Institutional Use Only.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Information for Patients
- Suicidal Thinking and Behavior - Patients, their caregivers, and families should be counseled that AEDs, including Mysoline, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
- Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see Usage in Pregnancy section).
- Please refer to the Primidone Medication Guide for more information.
# Precautions with Alcohol
- Alcohol-Primidone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Mysoline
# Look-Alike Drug Names
- A® — B®[1]
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Primidone | |
54e112708c3d25714bcd4ca57c6568e5b2539fe9 | wikidoc | Progabide | Progabide
# Overview
Progabide (INN) (trade name Gabrene, Sanofi-Aventis) is an analog and prodrug of gamma-aminobutyric acid used in the treatment of epilepsy. It has agonistic activity at the GABAA, GABAB, and GABAρ receptors.
# Uses
Progabide is approved in France for either monotherapy or adjunctive use in the treatment of epilepsy—specifically, generalized tonic-clonic, myoclonic, partial, and Lennox-Gastaut syndrome seizures—in both children and adults.
Progabide has been investigated for many diseases besides epilepsy, including Parkinson's disease, schizophrenia, clinical depression, anxiety disorder and spasticity with various levels of success.
In 1987, Bartolini and colleagues reported progabide's actions on dopamine to be contradictory, decreasing dopamine release, dopamine receptor density and postsynaptic receptor responsivity to dopamine while reducing striatal cholinergic activity so as to increase dopaminergic effects. Bartholini and colleagues concluded that it was this that caused Parkinson's patients in human clinical trials to either see an improvement in their Parkinson's with a worsening of L-dopa dyskinesia or an improvement in dyskinesia but with sometimes aggravated Parkinson's symptoms. The cholinergic effect takes only a single injection to achieve in rats; when given with haloperidol, the development of tolerance to haloperidol's cataleptic effects did not develop. It was hoped that this would be effective for tardive dyskinesia. However, Soares, Rathbone and Deeks wrote in the 2004 issue of The Cochrane Database of Systematic Reviews that "Any possible benefits are likely to be outweighed by the adverse effects associated with their use."
In addition to being tested for antipsychotic-induced tardive dyskinesia, progabide was itself tested as an antipsychotic; as early as 1979, it was obvious that it was ineffective for psychosis. While progabide may have been devoid of antipsychotic effects, it did have the effect in schizoaffective and hebephrenic patients of improving environmental responsiveness and social interactions.
# Synthesis | Progabide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Progabide (INN) (trade name Gabrene, Sanofi-Aventis) is an analog and prodrug of gamma-aminobutyric acid used in the treatment of epilepsy. It has agonistic activity at the GABAA, GABAB, and GABAρ receptors.
# Uses
Progabide is approved in France for either monotherapy or adjunctive use in the treatment of epilepsy—specifically, generalized tonic-clonic, myoclonic, partial, and Lennox-Gastaut syndrome seizures—in both children and adults.
Progabide has been investigated for many diseases besides epilepsy, including Parkinson's disease, schizophrenia, clinical depression, anxiety disorder and spasticity with various levels of success.
In 1987, Bartolini and colleagues reported progabide's actions on dopamine to be contradictory, decreasing dopamine release, dopamine receptor density and postsynaptic receptor responsivity to dopamine while reducing striatal cholinergic activity so as to increase dopaminergic effects.[1] Bartholini and colleagues concluded that it was this that caused Parkinson's patients in human clinical trials to either see an improvement in their Parkinson's with a worsening of L-dopa dyskinesia or an improvement in dyskinesia but with sometimes aggravated Parkinson's symptoms.[1] The cholinergic effect takes only a single injection to achieve in rats; when given with haloperidol, the development of tolerance to haloperidol's cataleptic effects did not develop.[2] It was hoped that this would be effective for tardive dyskinesia. However, Soares, Rathbone and Deeks wrote in the 2004 issue of The Cochrane Database of Systematic Reviews that "Any possible benefits are likely to be outweighed by the adverse effects associated with their [GABAergic agents'] use."[3]
In addition to being tested for antipsychotic-induced tardive dyskinesia, progabide was itself tested as an antipsychotic; as early as 1979, it was obvious that it was ineffective for psychosis.[4] While progabide may have been devoid of antipsychotic effects, it did have the effect in schizoaffective and hebephrenic patients of improving environmental responsiveness and social interactions.[5]
# Synthesis | https://www.wikidoc.org/index.php/Progabide | |
1ca00ed009667fd793a6a7f6cc8300a575874c68 | wikidoc | Progestin | Progestin
A progestin is a synthetic progestogen that has some biological activity similar to progesterone.
The two most frequent uses of progestins are for hormonal contraception (either alone or with an estrogen), and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy. Progestins are also used to treat secondary amenorrhea, dysfunctional uterine bleeding and endometriosis,
and as palliative treatment of endometrial cancer, renal cell carcinoma, breast cancer, and prostate cancer. High dose megestrol acetate is used to treat anorexia, cachexia and AIDS-related wasting.
Progesterone (or sometimes the progestin dydrogesterone or 17α-hydroxyprogesterone caproate) is used for luteal support in IVF protocols, questionably for treatment of
recurrent pregnancy loss, and for prevention of preterm birth in pregnant women with a history of at least one spontaneous preterm birth.
# History
The recognition of progesterone's ability to suppress ovulation during pregnancy spawned a search for a similar hormone that could bypass the problems associated with administering progesterone (low bioavailability when administered orally and local irritation and pain when continually administered parentally) and, at the same time, serve the purpose of controlling ovulation. The many synthetic hormones that resulted are known as progestins.
The first orally active progestin, ethisterone (pregneninolone, 17α-ethynyltestosterone), the 17α-ethynyl analog of testosterone, synthesized in 1938 by Hans Herloff Inhoffen, Willy Logemann, Walter Hohlweg and Arthur Serini at Schering AG in Berlin, was marketed in Germany in 1939 as Proluton C and by Schering in the U.S. in 1945 as Pranone
A more potent orally active progestin, norethisterone (norethindrone, 19-nor-17α-ethynyltestosterone), the 19-nor analog of ethisterone, synthesized in 1951 by Carl Djerassi, Luis Miramontes, and George Rosenkranz at Syntex in Mexico City, was marketed by Parke-Davis in the U.S. in 1957 as Norlutin, and was used as the progestin in some of the first oral contraceptives (Ortho-Novum, Norinyl, etc.) in the early 1960s.
Norethynodrel, an isomer of norethisterone, was synthesized in 1952 by Frank B. Colton at Searle in Skokie, Illinois and used as the progestin in Enovid, marketed in the U.S. in 1957 and approved as the first oral contraceptive in 1960.
# Examples
Some examples of progestins that have been used in hormonal contraceptives are norethynodrel (Enovid), norethindrone (many brand names, most notably Ortho-Novum and Ovcon) norgestimate (Ortho Tricyclen, Ortho-Cyclen), norgestrel, levonorgestrel (Alesse, Trivora-28), medroxyprogesterone (Provera, Depo-Provera) and desogestrel.
# Methods of progestin-based contraception
It has been found that the most effective method of contraception was with a combination of estrogen and progestin. This can be done in a monophasic, biphasic, or in a triphasic manner. In the monophasic method, both an estrogen and a progestin are administered for 20 or 21 days and stopped for a 7 or 8 day period that includes the 5 day menstrual period. Sometimes, a 28 day regimen is used that includes 6 or 7 inert tablets. Newer biphasic and triphasic methods are now used to more closely simulate the normal menstrual cycle. Yet another method is to administer a small dose of progestin only (no estrogen) in order to decrease certain risks associated with administering estrogen, but a major side effect is irregular bleeding that is usually observed during the first 18 months of such therapy.
# See Also
List of steroid abbreviations | Progestin
A progestin is a synthetic progestogen that has some biological activity similar to progesterone.
The two most frequent uses of progestins are for hormonal contraception (either alone or with an estrogen), and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy. Progestins are also used to treat secondary amenorrhea, dysfunctional uterine bleeding and endometriosis,
and as palliative treatment of endometrial cancer, renal cell carcinoma, breast cancer, and prostate cancer. High dose megestrol acetate is used to treat anorexia, cachexia and AIDS-related wasting.
Progesterone (or sometimes the progestin dydrogesterone or 17α-hydroxyprogesterone caproate) is used for luteal support in IVF protocols, questionably for treatment of
recurrent pregnancy loss, and for prevention of preterm birth in pregnant women with a history of at least one spontaneous preterm birth.[1]
# History
The recognition of progesterone's ability to suppress ovulation during pregnancy spawned a search for a similar hormone that could bypass the problems associated with administering progesterone (low bioavailability when administered orally and local irritation and pain when continually administered parentally) and, at the same time, serve the purpose of controlling ovulation. The many synthetic hormones that resulted are known as progestins.
The first orally active progestin, ethisterone (pregneninolone, 17α-ethynyltestosterone), the 17α-ethynyl analog of testosterone, synthesized in 1938 by Hans Herloff Inhoffen, Willy Logemann, Walter Hohlweg and Arthur Serini at Schering AG in Berlin, was marketed in Germany in 1939 as Proluton C and by Schering in the U.S. in 1945 as Pranone[2][3][4][5][6]
A more potent orally active progestin, norethisterone (norethindrone, 19-nor-17α-ethynyltestosterone), the 19-nor analog of ethisterone, synthesized in 1951 by Carl Djerassi, Luis Miramontes, and George Rosenkranz at Syntex in Mexico City, was marketed by Parke-Davis in the U.S. in 1957 as Norlutin, and was used as the progestin in some of the first oral contraceptives (Ortho-Novum, Norinyl, etc.) in the early 1960s.[3][3][4][5][6][7]
Norethynodrel, an isomer of norethisterone, was synthesized in 1952 by Frank B. Colton at Searle in Skokie, Illinois and used as the progestin in Enovid, marketed in the U.S. in 1957 and approved as the first oral contraceptive in 1960.[3][4][5][6][8]
# Examples
Some examples of progestins that have been used in hormonal contraceptives are norethynodrel (Enovid), norethindrone (many brand names, most notably Ortho-Novum and Ovcon) norgestimate (Ortho Tricyclen, Ortho-Cyclen), norgestrel, levonorgestrel (Alesse, Trivora-28), medroxyprogesterone (Provera, Depo-Provera) and desogestrel.
# Methods of progestin-based contraception
It has been found that the most effective method of contraception was with a combination of estrogen and progestin. This can be done in a monophasic, biphasic, or in a triphasic manner. In the monophasic method, both an estrogen and a progestin are administered for 20 or 21 days and stopped for a 7 or 8 day period that includes the 5 day menstrual period. Sometimes, a 28 day regimen is used that includes 6 or 7 inert tablets. Newer biphasic and triphasic methods are now used to more closely simulate the normal menstrual cycle. Yet another method is to administer a small dose of progestin only (no estrogen) in order to decrease certain risks associated with administering estrogen, but a major side effect is irregular bleeding that is usually observed during the first 18 months of such therapy.
# See Also
List of steroid abbreviations | https://www.wikidoc.org/index.php/Progestin | |
88b1a5238e4829545a35463fc17780397b0c872e | wikidoc | Prognosis | Prognosis
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctor's prediction of how a patient's disease will progress, and whether there is chance of recovery. Since the 20th century, the word has been increasingly used in non-medical contexts as well, for example in corporate finance.
# Methodology
## Disease and Prognostic Indicators
In medicine today, doctors search for methods of predicting how a patient (given their condition) may respond to treatment. Symptoms and tests may indicate favorable treatment with standard therapies. Likewise, a number of symptoms, health factors, and tests may indicate a less favorable treatment result with standard treatment - this may indicate that a more aggressive treatment plan may be desired.
Two areas where this type of prognosis prediction, or the use of prognostic indicators, is with Hodgkin's lymphoma and Non-Hodgkin lymphoma. Specifically with Non-Hodgkin lymphoma, physicians have developed the International Prognostic Index to predict patient outcome.
Prognostic scoring is also used for other cancer outcome predictions. A Manchester score is an indicator of prognosis in small cell lung cancer.
Other medical areas prognostic indicators are used is in Drug-Induced Liver Injury (DILI) (Hy's Law) and use of an exercise stress test as a prognostic indicator after myocardial infarction.
## End of Life
Large areas of medicine are still missing statistical figures on the exact prognosis - in these matters the doctor's previous experiences largely guides pronouncements in this matter. Medical studies have demonstrated that most doctors are overly optimistic when giving prognostic information, that is, they tend to overstate how long the patient might live. For patients who are critically ill, particularly those in an intensive care unit, there are numerical prognostic scoring systems that are more accurate. The most famous of these is the APACHE II scale. However, this scale is most accurate in the seven days prior to a patient's predicted death.
Knowing the prognosis helps determine whether it makes more sense to attempt certain treatments or to withhold them, and thus plays an important role in end-of-life decisions.
# History
For the great 19th century physicians, particularly the French school, the main aim of medicine was not to cure disease, but rather to diagnose it and achieve a satisfying prognosis of the patient's chances. Only several decades later did the focus of efforts in Western medicine shift to curing disease. | Prognosis
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctor's prediction of how a patient's disease will progress, and whether there is chance of recovery. Since the 20th century, the word has been increasingly used in non-medical contexts as well, for example in corporate finance.
# Methodology
## Disease and Prognostic Indicators
In medicine today, doctors search for methods of predicting how a patient (given their condition) may respond to treatment. Symptoms and tests may indicate favorable treatment with standard therapies. Likewise, a number of symptoms, health factors, and tests may indicate a less favorable treatment result with standard treatment - this may indicate that a more aggressive treatment plan may be desired.
Two areas where this type of prognosis prediction, or the use of prognostic indicators, is with Hodgkin's lymphoma and Non-Hodgkin lymphoma. Specifically with Non-Hodgkin lymphoma, physicians have developed the International Prognostic Index to predict patient outcome.
Prognostic scoring is also used for other cancer outcome predictions. A Manchester score is an indicator of prognosis in small cell lung cancer.
Other medical areas prognostic indicators are used is in Drug-Induced Liver Injury (DILI) (Hy's Law) and use of an exercise stress test as a prognostic indicator after myocardial infarction.
## End of Life
Large areas of medicine are still missing statistical figures on the exact prognosis - in these matters the doctor's previous experiences largely guides pronouncements in this matter. Medical studies have demonstrated that most doctors are overly optimistic when giving prognostic information, that is, they tend to overstate how long the patient might live. For patients who are critically ill, particularly those in an intensive care unit, there are numerical prognostic scoring systems that are more accurate. The most famous of these is the APACHE II scale. However, this scale is most accurate in the seven days prior to a patient's predicted death.
Knowing the prognosis helps determine whether it makes more sense to attempt certain treatments or to withhold them, and thus plays an important role in end-of-life decisions.
# History
For the great 19th century physicians, particularly the French school, the main aim of medicine was not to cure disease, but rather to diagnose it and achieve a satisfying prognosis of the patient's chances. Only several decades later did the focus of efforts in Western medicine shift to curing disease. | https://www.wikidoc.org/index.php/Prognosis | |
770d88520647604a1b4238783881454b78aa7cc0 | wikidoc | Pronation | Pronation
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Pronation is an anatomical term to describe a rotation movement. Such movement can occur in the forearm (at the radioulnar joint) and the foot (at the subtalar and talocalcaneonavicular joints).
For the forearm, when standing in the anatomical position pronation will move the palm of the hand from an anterior-facing position to a posterior-facing position without an associated movement at the shoulder (gleno-humeral joint). For the foot pronation will cause the sole of the foot to face more laterally than when standing in the anatomical position.
Pronation is the opposite of supination.
# Pronation of the Forearm
It is performed by the Pronator quadratus and Pronator teres muscle.
Pronation of the forearm should not be confused with medial rotation of the shoulder. When standing in the anatomical position, medial rotation of the shoulder can perform part of the movement to change the palm from facing anteriorly to posteriorly. Pronation of the forearm occurrs at the radioulnar joint so such a movement does not constitute it. To isolate medial rotation in the shoulder from pronation of the forearm one can stand with ones elbows tucked against the trunk, with the elbows flexed to 90 degrees with the forearms pointing directly in front of the body with the palms of the hands facing upwards. Keeping ones elbows tucked at the sides, the act of moving ones forearms so that the palms are facing downwards is pronation of the forearm.
# Pronation of the Foot
The pronated foot is one in which the heel bone angles inward and the arch tends to collapse. A "knock-kneed" person has overly pronated feet. This flattens the arch as the foot strikes the ground in order to absorb shock when the heel hits the ground, and to assist in balance during mid-stance. If habits develop, this action can lead to foot pain as well as knee pain, shin splints, achilles tendonitits and plantar fasciitis.. | Pronation
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Pronation is an anatomical term to describe a rotation movement[1]. Such movement can occur in the forearm (at the radioulnar joint) and the foot (at the subtalar and talocalcaneonavicular joints)[1][2].
For the forearm, when standing in the anatomical position pronation will move the palm of the hand from an anterior-facing position to a posterior-facing position without an associated movement at the shoulder (gleno-humeral joint). For the foot pronation will cause the sole of the foot to face more laterally than when standing in the anatomical position.
Pronation is the opposite of supination.
# Pronation of the Forearm
It is performed by the Pronator quadratus and Pronator teres muscle.
Pronation of the forearm should not be confused with medial rotation of the shoulder. When standing in the anatomical position, medial rotation of the shoulder can perform part of the movement to change the palm from facing anteriorly to posteriorly. Pronation of the forearm occurrs at the radioulnar joint so such a movement does not constitute it. To isolate medial rotation in the shoulder from pronation of the forearm one can stand with ones elbows tucked against the trunk, with the elbows flexed to 90 degrees with the forearms pointing directly in front of the body with the palms of the hands facing upwards. Keeping ones elbows tucked at the sides, the act of moving ones forearms so that the palms are facing downwards is pronation of the forearm.
# Pronation of the Foot
The pronated foot is one in which the heel bone angles inward and the arch tends to collapse. A "knock-kneed" person has overly pronated feet. This flattens the arch as the foot strikes the ground in order to absorb shock when the heel hits the ground, and to assist in balance during mid-stance. If habits develop, this action can lead to foot pain as well as knee pain, shin splints, achilles tendonitits and plantar fasciitis.[3]. | https://www.wikidoc.org/index.php/Pronate | |
fca0c8b5ac9a39180b7158e70f2132121efb127b | wikidoc | Prontosil | Prontosil
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
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Prontosil, the first commercially available antibacterial with a relatively broad effect (against Gram-positive cocci but not against enterobacteria), was developed by a research team at the Bayer Laboratories of the I.G. Farben conglomerate in Germany. The discovery and development of this first sulfonamide drug opened a new era in medicine.
Sulfonamidochrysoidine (KI-730), first synthesized by Bayer chemists Josef Klarer and Fritz Mietzsch, was tested and found effective against some important bacterial infections in mice by Gerhard Domagk, who subsequently received the 1939 Nobel Prize in Medicine. Prontosil was the result of five years of research and testing involving thousands of compounds related to azo dyes.
The crucial test result (in a murine model of Streptococcus pyogenes systemic infection) that preliminarily established the antibacterial efficacy of prontosil in mice dates from late December 1931. The readily water-soluble sodium salt of sulfonamidochrysoidine, which gives a burgundy red solution and was trademarked Prontosil, was clinically investigated between 1932 and 1934, first at the nearby hospital at Wuppertal-Elberfeld headed by Philipp Klee, and then at the Düsseldorf university hospital. The results were published in a series of articles in the February 15, 1935 issue of Germany's then pre-eminent medical scientific journal, Deutsche Medizinische Wochenschrift, and were initially received with some scepticism by a medical community bent on vaccination and crude immunotherapy.
As impressive clinical successes with Prontosil started to be reported from all over Europe, and especially after the widely published treatment of Franklin Delano Roosevelt, Jr. (a son of U.S. president Franklin D. Roosevelt), acceptance was quick and dozens of medicinal chemistry teams set out to improve on Prontosil. Jacques and Thérèse Trefouel and their team at the French Pasteur Institute found in 1936 that Prontosil is metabolized to sulfanilimide (para-aminophenylsulfonamide), a much simpler, colorless molecule, redefining Prontosil as a prodrug.
Sulfanilamide was already off patent (it had first been synthesized by Paul Gelmo, a chemistry student working at the University of Vienna in his 1909 thesis who however had not realized its medical potential) and cheap to produce. The sulfanilamide moiety was also easy to link into other molecules, and soon gave rise to hundreds of second-generation sulfonamide drugs. As a result, Prontosil failed to make the profits in the marketplace hoped for by Bayer. Although quickly eclipsed by these newer "sulfa drugs" and, in the mid-1940s and through the 1950s, penicillin and a string of newer antibiotics that proved more effective against more types of bacteria, Prontosil remained on the market until the 1960s. Prontosil's discovery ushered in the era of antibiotics and had a profound impact on pharmaceutical research, drug laws, and medical history.
Sulfonamide-trimethoprim combinations are used extensively for opportunistic infections in patients with AIDS, urinary infections and burn therapy. However their uses are greatly replaced by beta-lactam antibiotics.
de:Prontosil
it:Prontosil
nl:Prontosil | Prontosil
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Prontosil, the first commercially available antibacterial with a relatively broad effect (against Gram-positive cocci but not against enterobacteria), was developed by a research team at the Bayer Laboratories of the I.G. Farben conglomerate in Germany. The discovery and development of this first sulfonamide drug opened a new era in medicine.
Sulfonamidochrysoidine (KI-730), first synthesized by Bayer chemists Josef Klarer and Fritz Mietzsch, was tested and found effective against some important bacterial infections in mice by Gerhard Domagk, who subsequently received the 1939 Nobel Prize in Medicine. Prontosil was the result of five years of research and testing involving thousands of compounds related to azo dyes.
The crucial test result (in a murine model of Streptococcus pyogenes systemic infection) that preliminarily established the antibacterial efficacy of prontosil in mice dates from late December 1931. The readily water-soluble sodium salt of sulfonamidochrysoidine, which gives a burgundy red solution and was trademarked Prontosil, was clinically investigated between 1932 and 1934, first at the nearby hospital at Wuppertal-Elberfeld headed by Philipp Klee, and then at the Düsseldorf university hospital. The results were published in a series of articles in the February 15, 1935 issue of Germany's then pre-eminent medical scientific journal, Deutsche Medizinische Wochenschrift, and were initially received with some scepticism by a medical community bent on vaccination and crude immunotherapy.
As impressive clinical successes with Prontosil started to be reported from all over Europe, and especially after the widely published treatment of Franklin Delano Roosevelt, Jr. (a son of U.S. president Franklin D. Roosevelt), acceptance was quick and dozens of medicinal chemistry teams set out to improve on Prontosil. Jacques and Thérèse Trefouel and their team at the French Pasteur Institute found in 1936 that Prontosil is metabolized to sulfanilimide (para-aminophenylsulfonamide), a much simpler, colorless molecule, redefining Prontosil as a prodrug.
Sulfanilamide was already off patent (it had first been synthesized by Paul Gelmo, a chemistry student working at the University of Vienna in his 1909 thesis who however had not realized its medical potential) and cheap to produce. The sulfanilamide moiety was also easy to link into other molecules, and soon gave rise to hundreds of second-generation sulfonamide drugs. As a result, Prontosil failed to make the profits in the marketplace hoped for by Bayer. Although quickly eclipsed by these newer "sulfa drugs" and, in the mid-1940s and through the 1950s, penicillin and a string of newer antibiotics that proved more effective against more types of bacteria, Prontosil remained on the market until the 1960s. Prontosil's discovery ushered in the era of antibiotics and had a profound impact on pharmaceutical research, drug laws, and medical history.
Sulfonamide-trimethoprim combinations are used extensively for opportunistic infections in patients with AIDS, urinary infections and burn therapy. However their uses are greatly replaced by beta-lactam antibiotics.
Template:SulfonamideAntiBiotics
Template:SIB
de:Prontosil
it:Prontosil
nl:Prontosil
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Prontosil | |
86217ed2ce6c7a63aa267cf27638f653bf8bf413 | wikidoc | Properdin | Properdin
Properdin is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. It is found in the blood serum of more complex animals.
# Structure
Properdin is a gamma globulin protein composed of multiple identical protein subunits with a separate ligand-binding site. Native properdin occurs in head-to-tail dimers, trimers and tetramers in the fixed ratio 22:52:28.
# Function
It is known that it participates in some specific immune responses. It plays a part in tissue inflammation as well as the engulfing of pathogens by phagocytes. In addition it is known to help to neutralize some viruses.
The properdin promotes the association of C3b with Factor B and provides a focal point for the assembly of C3bBb on a surface. It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H – mediated cleavage of C3b by Factor I.
The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune complexes and bacterial endotoxins, polysaccharides, and cell walls, and results in producing anaphylatoxins, opsonins, chemotactic factors, and the membrane attack complex, all of which help fight pathogens.
# History
Properdin was discovered in 1954 by Dr. Louis Pillemer of the Institute of Pathology (now the Department of Pathology at Case Western Reserve University).
# Deficiency
Properdin deficiency is a rare X-linked disease in which properdin is deficient. Affected individuals are susceptible to fulminant meningococcal disease. | Properdin
Properdin is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. It is found in the blood serum of more complex animals.
# Structure
Properdin is a gamma globulin protein composed of multiple identical protein subunits with a separate ligand-binding site. Native properdin occurs in head-to-tail dimers, trimers and tetramers in the fixed ratio 22:52:28.[1]
# Function
It is known that it participates in some specific immune responses. It plays a part in tissue inflammation as well as the engulfing of pathogens by phagocytes. In addition it is known to help to neutralize some viruses.
The properdin promotes the association of C3b with Factor B and provides a focal point for the assembly of C3bBb on a surface. It binds to preformed alternative pathway C3-convertases.[2] Properdin also inhibits the Factor H – mediated cleavage of C3b by Factor I.
The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune complexes and bacterial endotoxins, polysaccharides, and cell walls, and results in producing anaphylatoxins, opsonins, chemotactic factors, and the membrane attack complex, all of which help fight pathogens.
# History
Properdin was discovered in 1954 by Dr. Louis Pillemer of the Institute of Pathology (now the Department of Pathology at Case Western Reserve University).
# Deficiency
Properdin deficiency is a rare X-linked disease in which properdin is deficient. Affected individuals are susceptible to fulminant meningococcal disease.[3] | https://www.wikidoc.org/index.php/Properdin | |
6c6eb8d256547dc8af7754e9992c59985e2549b4 | wikidoc | Protamine | Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in the spermatozoon than histones, but they must be decompressed before the genetic data can be used for protein synthesis. However, in humans and maybe other primates, 10-15% of the sperm's genome is packaged by histones thought to bind genes that are essential for early embryonic development.
# Spermatogenesis
During the formation of sperm, protamine binds to the phosphate backbone of DNA using the arginine-rich domain as an anchor. DNA is then folded into a toroid, an O-shaped structure, although the mechanism is not known. A sperm cell can contain up to 50,000 toroid-shaped structures in its nucleus with each toroid containing about 50 kilobases. Before the toroid is formed, histones are removed from the DNA by transition nuclear proteins, so that protamine can condense it. The effects of this change are 1) an increase in sperm hydrodynamics for better flow through liquids by reducing the head size 2) decrease in the occurrence of DNA damage 3) removal of the epigenetic markers that occur with histone modifications.
The structure of the sperm head is also related to protamine levels. The ratio of protamine 2 to protamine 1 and transition nuclear proteins has been found to change the sperm head shape in various species of mice, by altering the expression of protamine 2 via mutations in its promoter region. A decrease in the ratio has been found to increase the competitive ability of sperm in Mus species. However, further testing is required to determine how this ratio influences the shape of the head and whether monogamy influences this selection. In humans, studies show that men who have unbalanced Prm1/Prm2 are subfertile or infertile.
# Medical uses
When mixed with insulin, protamines slow down the onset and increase the duration of insulin action (see NPH insulin).
Protamine is used in cardiac surgery, vascular surgery, and interventional radiology procedures to neutralize the anti-clotting effects of heparin. Adverse effects include increased pulmonary artery pressure and decrease peripheral blood pressure, myocardial oxygen consumption, cardiac output, and heart rate.
Protamine sulfate is an antidote for heparin overdose. A chain shortened version of protamine also acts as a potent heparin antagonist, but with markedly reduced antigenicity.
In gene therapy, protamine sulfate's ability to condense plasmid DNA along with its approval by the U.S. Food and Drug Administration (FDA) have made it an appealing candidate to increase transduction rates by both viral and nonviral (e.g. utilizing cationic liposomes) mediated delivery mechanisms.
Protamine may be used as a drug to prevent obesity. Protamine has been shown to deter increases in body weight and low-density lipoprotein in high-fat diet rats. This effect occurs through the inhibition of lipase activity, an enzyme responsible for triacylglycerol digestion and absorption, resulting in a decrease in the absorption of dietary fat. No liver damage was found when the rats were treated with protamine. However, emulsification of long-chain fatty acids for digestion and absorption in the small intestine is less constant in humans than rats, which will vary the effectiveness of protamine as a drug. Furthermore, human peptidases may degrade protamine at different rates, thus further tests are required to determine protamine’s ability to prevent obesity in humans.
# Examples
Mice, humans and certain fish have two or more different protamines, whereas the sperm of bull and boar, have one form of protamine due to a mutation in the PRM2 gene. In the rat, although the gene for PRM2 is present, expression of this protein is extremely small because of limited transcription due to an inefficient promoter in addition to altered processing of the mRNA transcript.
## Human
The 2 human protamines are denoted PRM1 and PRM2.
## Fish
Examples of protamines from fish are:
- salmine from salmon
- clupeine from herring sperm (Clupea)
- iridine from rainbow trout
- thinnine from tunafish (Thunnus)
- stelline from starry sturgeon (Acipenser stellatus)
- scylliorhinine from dogfish (Scylliorhinus)
# Protamine structure
The primary structure of protamine P1, the protamine used for packaging DNA in sperm cells, in placental mammals is usually 49 or 50 amino acids long. This sequence is divided into three separate domains: an arginine-rich domain for DNA binding flanked by shorter peptide sequences containing mostly cysteine residues. The arginine-rich domain consists of 3-11 arginine residues and is conserved between fish protamine and mammalian protamine 1 sequences at about 60-80% sequence identity.
After translation, the protamine P1 structure is immediately phosphorylated at all three of the above-mentioned domains. Another round of phosphorylation occurs when the sperm enters the egg, but the function of these phosphorylations is uncertain. When protamine P1 binds to DNA, cysteine from the amino terminal of one protamine P1 forms disulfide bonds with the cysteine from the carboxy-terminal of another protamine P1. The disulfide bonds function to prevent the dissociation of protamine P1 from DNA until the bonds are reduced when the sperm enters the egg.
The secondary and tertiary structure of protamine is not known with certainty, but several proposals have been published. | Protamine
Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in the spermatozoon than histones, but they must be decompressed before the genetic data can be used for protein synthesis. However, in humans and maybe other primates, 10-15% of the sperm's genome is packaged by histones thought to bind genes that are essential for early embryonic development.[1]
# Spermatogenesis
During the formation of sperm, protamine binds to the phosphate backbone of DNA using the arginine-rich domain as an anchor. DNA is then folded into a toroid, an O-shaped structure, although the mechanism is not known. A sperm cell can contain up to 50,000 toroid-shaped structures in its nucleus with each toroid containing about 50 kilobases.[2] Before the toroid is formed, histones are removed from the DNA by transition nuclear proteins, so that protamine can condense it. The effects of this change are 1) an increase in sperm hydrodynamics for better flow through liquids by reducing the head size 2) decrease in the occurrence of DNA damage 3) removal of the epigenetic markers that occur with histone modifications.[3]
The structure of the sperm head is also related to protamine levels. The ratio of protamine 2 to protamine 1 and transition nuclear proteins has been found to change the sperm head shape in various species of mice, by altering the expression of protamine 2 via mutations in its promoter region. A decrease in the ratio has been found to increase the competitive ability of sperm in Mus species. However, further testing is required to determine how this ratio influences the shape of the head and whether monogamy influences this selection. In humans, studies show that men who have unbalanced Prm1/Prm2 are subfertile or infertile.[4]
# Medical uses
When mixed with insulin, protamines slow down the onset and increase the duration of insulin action (see NPH insulin).[5]
Protamine is used in cardiac surgery, vascular surgery, and interventional radiology procedures to neutralize the anti-clotting effects of heparin. Adverse effects include increased pulmonary artery pressure and decrease peripheral blood pressure, myocardial oxygen consumption, cardiac output, and heart rate.[6]
Protamine sulfate is an antidote for heparin overdose.[7] A chain shortened version of protamine also acts as a potent heparin antagonist, but with markedly reduced antigenicity.[8]
In gene therapy, protamine sulfate's ability to condense plasmid DNA along with its approval by the U.S. Food and Drug Administration (FDA) have made it an appealing candidate to increase transduction rates by both viral[9] and nonviral (e.g. utilizing cationic liposomes)[10] mediated delivery mechanisms.
Protamine may be used as a drug to prevent obesity. Protamine has been shown to deter increases in body weight and low-density lipoprotein in high-fat diet rats. This effect occurs through the inhibition of lipase activity, an enzyme responsible for triacylglycerol digestion and absorption, resulting in a decrease in the absorption of dietary fat. No liver damage was found when the rats were treated with protamine. However, emulsification of long-chain fatty acids for digestion and absorption in the small intestine is less constant in humans than rats, which will vary the effectiveness of protamine as a drug. Furthermore, human peptidases may degrade protamine at different rates, thus further tests are required to determine protamine’s ability to prevent obesity in humans.[11]
# Examples
Mice, humans[1] and certain fish have two or more different protamines, whereas the sperm of bull and boar,[12] have one form of protamine due to a mutation in the PRM2 gene. In the rat, although the gene for PRM2 is present, expression of this protein is extremely small because of limited transcription due to an inefficient promoter in addition to altered processing of the mRNA transcript.[13]
## Human
The 2 human protamines are denoted PRM1 and PRM2.
## Fish
Examples of protamines from fish are:
- salmine from salmon
- clupeine from herring sperm (Clupea)
- iridine from rainbow trout
- thinnine from tunafish (Thunnus)
- stelline from starry sturgeon (Acipenser stellatus)
- scylliorhinine from dogfish (Scylliorhinus)
# Protamine structure
The primary structure of protamine P1, the protamine used for packaging DNA in sperm cells, in placental mammals is usually 49 or 50 amino acids long. This sequence is divided into three separate domains: an arginine-rich domain for DNA binding flanked by shorter peptide sequences containing mostly cysteine residues. The arginine-rich domain consists of 3-11 arginine residues and is conserved between fish protamine and mammalian protamine 1 sequences at about 60-80% sequence identity.[1]
After translation, the protamine P1 structure is immediately phosphorylated at all three of the above-mentioned domains. Another round of phosphorylation occurs when the sperm enters the egg, but the function of these phosphorylations is uncertain. When protamine P1 binds to DNA, cysteine from the amino terminal of one protamine P1 forms disulfide bonds with the cysteine from the carboxy-terminal of another protamine P1. The disulfide bonds function to prevent the dissociation of protamine P1 from DNA until the bonds are reduced when the sperm enters the egg.[1]
The secondary and tertiary structure of protamine is not known with certainty, but several proposals have been published.[14][15][16] | https://www.wikidoc.org/index.php/Protamine | |
ac10b0666ecd0a4a4da8dfe1b71685a55ebbfcd1 | wikidoc | Protandim | Protandim
Protandim is a patented dietary supplement that increases the body’s natural antioxidant defenses. According to the maker LifeVantage, Protandim is not an antioxidant per se, but provides antioxidant therapy by inducing the genes that encode a family of protective enzymes, including superoxide dismutase (SOD) and catalase (CAT). Protandim’s mechanism of action is to prevent free radical damage by increasing endogenous catalytic pathways, whereas traditional antioxidant supplements provide only stoichiometric scavenging of free radicals or other oxidants.
Basically, Protandim stimulates the body’s own antioxidant mechanisms instead of simply adding antioxidants to your diet like traditional consumable antioxidant supplements.
A peer-reviewed, published, human clinical trial of Protandim demonstrated its ability to induce erythrocyte SOD and CAT and to decrease lipid peroxidation products in the circulation associated with normal aging (see Clinical Study below). The age related increase in oxidative stress markers was completely eliminated. So while no one claims Protandim is a cure for aging, it has been shown to greatly reduce or eliminate certain biochemical processes associated with aging.
# Ingredients
Protandim is a composition of five botanicals (more specifically, phytonutrients) that act with synergy such that the combined effect exceeds the sum of the individual ingredient contributions. This synergy means that simply adding the five ingredients to your diet isn’t as effective as taking the Protandim supplement.
The ingredients include silymarin from Silybum marianum, bacopasides from Bacopa monniera, withanolides from Withania somnifera, polyphenolics from Camellja sinensis, and curcumin from Curcuma longa. These compounds have been widely studied, and function as adaptogens. These phytochemicals are derived from plants more commonly known as milk thistle, bacopa, ashwagandha, green tea, and turmeric.
# Clinical Study
The scientific evidence showing Protandim works is based on clinical study results using a TBARS (thiobarbituric acid reactive substances) measurement, which reflects the damage to cell membranes from oxidative stress. This damage is caused by free radicals that are produced by our own metabolic processes, and naturally increases as we age. Increased TBARS also occurs as a result of obesity, strenuous exercise and lifestyle choices not conducive to good health, such as a high fat diet.
In the clinical study with men and women taking Protandim for 30 days, a 40 percent average decrease in TBARS was reported, and maintained for 120 days when Protandim was taken every day. Additionally, Protandim significantly increased activity of SOD and CAT antioxidant enzymes by 30 percent and 54 percent respectively, substantially increasing the body’s antioxidant defenses.
According to the company’s website, additional human clinical trials are underway or are being designed to investigate Protandim's ability to treat a variety of health conditions related to oxidative stress. The areas of independent investigation include heart disease, liver disease, asthma, photoaging of the skin, osteoarthritis, metabolic syndrome, and muscular dystrophy.
# See Also
Antioxidants
Catalase
Dietary supplement
Duchenne Muscular Dystrophy
Free Radicals
Oxidative stress
Superoxide dismutase | Protandim
Protandim is a patented dietary supplement that increases the body’s natural antioxidant defenses. According to the maker LifeVantage, Protandim is not an antioxidant per se, but provides antioxidant therapy by inducing the genes that encode a family of protective enzymes, including superoxide dismutase (SOD) and catalase (CAT). Protandim’s mechanism of action is to prevent free radical damage by increasing endogenous catalytic pathways, whereas traditional antioxidant supplements provide only stoichiometric scavenging of free radicals or other oxidants.
Basically, Protandim stimulates the body’s own antioxidant mechanisms instead of simply adding antioxidants to your diet like traditional consumable antioxidant supplements.
A peer-reviewed, published, human clinical trial of Protandim demonstrated its ability to induce erythrocyte SOD and CAT and to decrease lipid peroxidation products in the circulation associated with normal aging (see Clinical Study below). The age related increase in oxidative stress markers was completely eliminated. So while no one claims Protandim is a cure for aging, it has been shown to greatly reduce or eliminate certain biochemical processes associated with aging.
# Ingredients
Protandim is a composition of five botanicals (more specifically, phytonutrients) that act with synergy such that the combined effect exceeds the sum of the individual ingredient contributions. This synergy means that simply adding the five ingredients to your diet isn’t as effective as taking the Protandim supplement.
The ingredients include silymarin from Silybum marianum, bacopasides from Bacopa monniera, withanolides from Withania somnifera, polyphenolics from Camellja sinensis, and curcumin from Curcuma longa. These compounds have been widely studied, and function as adaptogens. These phytochemicals are derived from plants more commonly known as milk thistle, bacopa, ashwagandha, green tea, and turmeric.
# Clinical Study
The scientific evidence showing Protandim works is based on clinical study results using a TBARS (thiobarbituric acid reactive substances) measurement, which reflects the damage to cell membranes from oxidative stress. This damage is caused by free radicals that are produced by our own metabolic processes, and naturally increases as we age. Increased TBARS also occurs as a result of obesity, strenuous exercise and lifestyle choices not conducive to good health, such as a high fat diet.
In the clinical study with men and women taking Protandim for 30 days, a 40 percent average decrease in TBARS was reported, and maintained for 120 days when Protandim was taken every day. Additionally, Protandim significantly increased activity of SOD and CAT antioxidant enzymes by 30 percent and 54 percent respectively, substantially increasing the body’s antioxidant defenses.
According to the company’s website, additional human clinical trials are underway or are being designed to investigate Protandim's ability to treat a variety of health conditions related to oxidative stress. The areas of independent investigation include heart disease, liver disease, asthma, photoaging of the skin, osteoarthritis, metabolic syndrome, and muscular dystrophy.
# See Also
Antioxidants
Catalase
Dietary supplement
Duchenne Muscular Dystrophy
Free Radicals
Oxidative stress
Superoxide dismutase | https://www.wikidoc.org/index.php/Protandim | |
f9bace77e0ab2cf6dce469efee968a20abc65928 | wikidoc | Protein Z | Protein Z
Protein Z (PZ or PROZ) is a protein which in humans is encoded by the PROZ gene.
Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.
# Physiology
Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.
# Genetics
It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).
It has four domains: a gla-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.
# History
Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977, and Broze & Miletich determined it in human plasma in 1984.
# Structure
Structural analysis of protein Z will allow better understanding of its function. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs. | Protein Z
Protein Z (PZ or PROZ) is a protein which in humans is encoded by the PROZ gene.[2][3]
Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.
# Physiology
Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.
# Genetics
It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).
It has four domains: a gla-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.
# History
Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977,[4] and Broze & Miletich determined it in human plasma in 1984.[5]
# Structure
Structural analysis of protein Z will allow better understanding of its function. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.[1] | https://www.wikidoc.org/index.php/Protein_Z | |
21c43e11f0de7bab11b32ad90514162983d4c6a2 | wikidoc | Pseudopod | Pseudopod
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 to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Pseudopods or pseudopodia (false feet) are temporary projections of eukaryotic cells. Cells having this faculty are generally referred to as amoeboids.
# Formation
First, the cell surface extends a membrane process, termed a lamellipodium. Polymerization of actin takes place and form filaments at the leading edge, which subsequently will blend into one another to form networks. It is supposed that actin polymerization is at the origin of the force propelling the cell forwards.
# Function
### Mechanical role
Pseudopods are one of the three locomotion modes of unicellular organisms (together with flagella and cilia).
# Morphology
Pseudopods can be classified into several varieties according to their appearance:
- Lobopodia are bulbous, short and blunt in form, very typical of Amoebozoa.
- Fillopodia are more slender and filiform with pointed ends, consisting mainly of ectoplasm. These formations are supported by microfilaments.
- Reticulopodia, also known as reticulose pseudopods, are complex formations where individual pseudopods are blended together and form irregular nets.
- Axopodia are thin pseudopods containing complex arrays of microtubules and are enveloped by cytoplasm. Axopodia are responsible for phagocytosis, by rapidly retracting in response to physical contacts. They are observed in radiolaria and heliozoa. This obviously takes a strain on the helix for after the sensory action has occurred, it then later on dies. | Pseudopod
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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# Overview
Pseudopods or pseudopodia (false feet) are temporary projections of eukaryotic cells. Cells having this faculty are generally referred to as amoeboids.
# Formation
First, the cell surface extends a membrane process, termed a lamellipodium. Polymerization of actin takes place and form filaments at the leading edge, which subsequently will blend into one another to form networks. It is supposed that actin polymerization is at the origin of the force propelling the cell forwards.
# Function
### Mechanical role
Pseudopods are one of the three locomotion modes of unicellular organisms (together with flagella and cilia).
# Morphology
Pseudopods can be classified into several varieties according to their appearance:
- Lobopodia are bulbous, short and blunt in form, very typical of Amoebozoa.
- Fillopodia are more slender and filiform with pointed ends, consisting mainly of ectoplasm. These formations are supported by microfilaments.
- Reticulopodia, also known as reticulose pseudopods, are complex formations where individual pseudopods are blended together and form irregular nets.
- Axopodia are thin pseudopods containing complex arrays of microtubules and are enveloped by cytoplasm. Axopodia are responsible for phagocytosis, by rapidly retracting in response to physical contacts. They are observed in radiolaria and heliozoa. This obviously takes a strain on the helix for after the sensory action has occurred, it then later on dies.
Template:SIB
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Pseudopod | |
253eb15bffd5fcb187acac291c85422f807591dd | wikidoc | Psilocybe | Psilocybe
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There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Psilocybe is a genus of small mushrooms growing worldwide. This genus is best known for its species with hallucinogenic properties, widely known as "magic mushrooms", though the majority of species do not contain hallucinogenic compounds. Psilocin and psilocybin are the hallucinogenic compounds responsible for the psychoactive effects of many species in the genus.
The word psilocybe comes from the Greek words ψιλος + κυβη and literally means "bare headed", referring to the mushroom's plain cap. It may be pronounced with the accent on the first syllable (IPA Template:IPA; MWCD Template:IPA) or the second (IPA Template:IPA; MWCD Template:IPA). The final e is not silent. The marked difference between the Botanical Latin-based pronunciation (given here) and anglicized colloquial pronunciations (with a silent "e") is sometimes a source of confusion in oral communication about this genus.
# Description
Psilocybe fruiting bodies are typically small, non-descript mushrooms with a typical "little brown mushroom" morphology. Macroscopically, they are characterized by their small to occasionally medium size, brown to yellow-brown coloration, with a typically hygrophanous pileus, and a spore print-color that ranges from lilac-brown to dark purple-brown (though rusty-brown colored varieties are known in at least one species). Hallucinogenic species typically have a blue-staining reaction when the fruiting body is bruised. Microscopically, they are characterized by cutis-type pileipellis, lack of chrysocystidia, and spores that are smooth, ellipsoid to rhomboid to subhexagonal in shape, with a distinct apical germ pore. Ecologically, all species of Psilocybe are saprotrophs, growing on various kinds of decaying organic matter.
# Classification
A recent study of the molecular phylogeny of the agarics by Moncalvo et al, indicates that the genus Psilocybe as presently defined is polyphyletic, falling into two distinct clades that are not directly related to each other. The blue-staining hallucinogenic species constitute one clade and the non-bluing species constitute the other. The type species (Psilocybe montana) is in the non-bluing clade.
Psilocybe is placed taxonomically in the agaric family Strophariaceae based upon its spore and pileipellis morphology. However, molecular studies indicate that the Strophariaceae may be a polyphyletic grouping of several clades that are fairly close to each other, but not necessarily sister taxa, hence, the precise relationship of Psilocybe to other agaric genera awaits further study. The phylogenetic study by Moncalvo, et al. has confirmed that the agaric genus Melanotus is simply a subgroup of the non-bluing Psilocybe, and also points to a close relationship between the latter group and the genera Kuehneromyces and Phaeogalera.
# Distribution and habitat
Geographically, species in this genus are found throughout the world in most biomes, with the exception of high deserts. 60 species of Psilocybe occur in the United States, of which 25 are hallucinogenic. For the bluing Psilocybe, the greatest species diversity seems to be in the neotropics, from Mesoamerica through Brazil and Chile. Psilocybe are found in a variety of habitats and substrates. Many of the bluing species found in temperate regions, such as Psilocybe cyanescens, seem to have an affinity for landscaped areas mulched with woodchips and are actually rather rare in natural settings removed from human habitation. Contrary to popular belief, only a minority of Psilocybe species, such as P. coprophila and P. cubensis, grow directly on dung. Many other species are found in habitats such as mossy, grassy, or forest humus soils.
# Psychoactivity
## Biochemistry and pharmacology
The blue-staining species of Psilocybe are characterized by the presence of psilocin and psilocybin. The blue-staining reaction, while not completely understood, is thought to be a caused by a degradation reaction of psilocin, hence the degree of bluing in a Psilocybe fruiting body correlates directly with the concentration of psilocin in the mushroom. Psilocybin is chemically far more stable than psilocin, the latter compound being largely lost when the mushroom is heated or dried.
(See Psilocybin for a more in-depth discussion of the pharmacology of psilocybin and psilocin.)
Some psychoactive species contain baeocystin and norbaeocystin in addition to psilocin and psilocybin.
## Medical and psychiatric aspects
Among some groups of Mesoamerican natives, hallucinogenic Psilocybe have been used by native healers for centuries for divining the causes of illness and as part of psychological counseling. Contemporary researchers have generally preferred to use purified psilocybin in medical and psychiatric research, though in practice, whole Psilocybe cubensis is often used.
For details on contemporary research, see: Psilocybin: Medicine.
# History and ethnography
Hallucinogenic species of Psilocybe have a long history of use among the native peoples of Mesoamerica for religious communion, divination, and healing, from pre-Columbian times up to the present day. Hallucinogenic Psilocybe were known to the Mexicans as teonanácatl (literally "god mushroom") and were reportedly served at the coronation of Moctezuma II in 1502. After the Spanish conquest, the use of hallucinogenic plants and mushrooms, like other pre-Christian traditions, was forcibly suppressed and driven underground.
By the twentieth century, hallucinogenic mushroom use was thought by non-Indians to have disappeared entirely. However, in 1955, Valentina and R. Gordon Wasson became the first Westerners to actively participate in an indigenous mushroom ceremony. The Wassons did much to publicize their discovery, even publishing an article on their experiences in Life in 1957. In 1956, Roger Heim identified the hallucinogenic mushroom that the Wassons had brought back from Mexico as Psilocybe and in 1958, Albert Hofmann first identified psilocin and psilocybin as the active compound in these mushrooms.
At present, hallucinogenic mushroom use has been reported among a number of groups spanning from central Mexico to Oaxaca, including groups of Nahua, Mixtecs, Mixe, Mazatecs, Zapotecs, and others.
The popularization of entheogens by Wasson, Timothy Leary, and others has led to an explosion in the use of hallucinogenic Psilocybe throughout the world. By the early 1970s, a number of psychoactive Psilocybe species were described from temperate North America, Europe, and Asia and were widely collected. Books describing methods of cultivating Psilocybe cubensis in large quantities were also published. The relatively easy availability of hallucinogenic Psilocybe from wild and cultivated sources has made it among the most widely used of the hallucinogenic drugs.
# Legal status
Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances. Schedule I drugs are drugs with a high potential for abuse that have no recognized medical uses. This status is reflected in the drug laws of the majority of the world's nations. Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there is a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places. The legal status of Psilocybe spores is even more ambiguous, as the spores contain neither psilocybin nor psilocin, and hence are not illegal to sell or possess in many jurisdictions, though many jurisdictions will prosecute under broader laws prohibiting items that are used in drug manufacture. A few jurisdictions (such as the US states of California, Georgia, and Idaho) have specifically prohibited the sale and possession of psilocybin mushroom spores. Cultivation of psilocybin mushrooms is considered drug manufacture in most jurisdictions and is often severely penalized, though some countries and one US state have ruled that growing psilocybin mushrooms does not qualify as "manufacturing" a controlled substance.
# Notable species
- Psilocybe cubensis, (= Stropharia cubensis); the most commonly grown and consumed Psilocybe, due to ease of cultivation and large size of carpophores; also commonly collected throughout the tropics and subtropics, including the US Gulf Coast; nicknamed the commercial psilocybe.
- Psilocybe semilanceata, found in northern temperate climates; nicknamed the liberty cap.
- Psilocybe cyanescens, native to the Pacific Northwest of North America, but also found in western Europe; nicknamed the wavy-cap or wavies.
- Psilocybe azurescens, a highly potent species native to Oregon, but popular in outdoor cultivation, and expanding its range as a result; nicknamed azies. | Psilocybe
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Psilocybe is a genus of small mushrooms growing worldwide. This genus is best known for its species with hallucinogenic properties, widely known as "magic mushrooms", though the majority of species do not contain hallucinogenic compounds. Psilocin and psilocybin are the hallucinogenic compounds responsible for the psychoactive effects of many species in the genus.
The word psilocybe comes from the Greek words ψιλος + κυβη and literally means "bare headed", referring to the mushroom's plain cap. It may be pronounced with the accent on the first syllable (IPA Template:IPA; MWCD Template:IPA) or the second (IPA Template:IPA; MWCD Template:IPA). The final e is not silent. The marked difference between the Botanical Latin-based pronunciation (given here) and anglicized colloquial pronunciations (with a silent "e") is sometimes a source of confusion in oral communication about this genus.
# Description
Psilocybe fruiting bodies are typically small, non-descript mushrooms with a typical "little brown mushroom" morphology. Macroscopically, they are characterized by their small to occasionally medium size, brown to yellow-brown coloration, with a typically hygrophanous pileus, and a spore print-color that ranges from lilac-brown to dark purple-brown (though rusty-brown colored varieties are known in at least one species[1]). Hallucinogenic species typically have a blue-staining reaction when the fruiting body is bruised. Microscopically, they are characterized by cutis-type pileipellis, lack of chrysocystidia, and spores that are smooth, ellipsoid to rhomboid to subhexagonal in shape, with a distinct apical germ pore. Ecologically, all species of Psilocybe are saprotrophs, growing on various kinds of decaying organic matter.[2] [3]
# Classification
A recent study of the molecular phylogeny of the agarics by Moncalvo et al,[4] indicates that the genus Psilocybe as presently defined is polyphyletic, falling into two distinct clades that are not directly related to each other. The blue-staining hallucinogenic species constitute one clade and the non-bluing species constitute the other. The type species (Psilocybe montana) is in the non-bluing clade.
Psilocybe is placed taxonomically in the agaric family Strophariaceae based upon its spore and pileipellis morphology. However, molecular studies indicate that the Strophariaceae may be a polyphyletic grouping of several clades that are fairly close to each other, but not necessarily sister taxa, hence, the precise relationship of Psilocybe to other agaric genera awaits further study. The phylogenetic study by Moncalvo, et al.[4] has confirmed that the agaric genus Melanotus is simply a subgroup of the non-bluing Psilocybe, and also points to a close relationship between the latter group and the genera Kuehneromyces and Phaeogalera.
# Distribution and habitat
Geographically, species in this genus are found throughout the world in most biomes, with the exception of high deserts. 60 species of Psilocybe occur in the United States, of which 25 are hallucinogenic. [2] For the bluing Psilocybe, the greatest species diversity seems to be in the neotropics, from Mesoamerica through Brazil and Chile.[2] Psilocybe are found in a variety of habitats and substrates. Many of the bluing species found in temperate regions, such as Psilocybe cyanescens, seem to have an affinity for landscaped areas mulched with woodchips and are actually rather rare in natural settings removed from human habitation. Contrary to popular belief, only a minority of Psilocybe species, such as P. coprophila and P. cubensis, grow directly on dung. Many other species are found in habitats such as mossy, grassy, or forest humus soils.
# Psychoactivity
## Biochemistry and pharmacology
The blue-staining species of Psilocybe are characterized by the presence of psilocin and psilocybin. The blue-staining reaction, while not completely understood, is thought to be a caused by a degradation reaction of psilocin, hence the degree of bluing in a Psilocybe fruiting body correlates directly with the concentration of psilocin in the mushroom. Psilocybin is chemically far more stable than psilocin, the latter compound being largely lost when the mushroom is heated or dried.
(See Psilocybin for a more in-depth discussion of the pharmacology of psilocybin and psilocin.)
Some psychoactive species contain baeocystin and norbaeocystin in addition to psilocin and psilocybin.
## Medical and psychiatric aspects
Among some groups of Mesoamerican natives, hallucinogenic Psilocybe have been used by native healers for centuries for divining the causes of illness and as part of psychological counseling. Contemporary researchers have generally preferred to use purified psilocybin in medical and psychiatric research, though in practice, whole Psilocybe cubensis is often used.
For details on contemporary research, see: Psilocybin: Medicine.
# History and ethnography
Hallucinogenic species of Psilocybe have a long history of use among the native peoples of Mesoamerica for religious communion, divination, and healing, from pre-Columbian times up to the present day. Hallucinogenic Psilocybe were known to the Mexicans as teonanácatl (literally "god mushroom") and were reportedly served at the coronation of Moctezuma II in 1502. After the Spanish conquest, the use of hallucinogenic plants and mushrooms, like other pre-Christian traditions, was forcibly suppressed and driven underground.
By the twentieth century, hallucinogenic mushroom use was thought by non-Indians to have disappeared entirely. However, in 1955, Valentina and R. Gordon Wasson became the first Westerners to actively participate in an indigenous mushroom ceremony. The Wassons did much to publicize their discovery, even publishing an article on their experiences in Life in 1957.[5] In 1956, Roger Heim identified the hallucinogenic mushroom that the Wassons had brought back from Mexico as Psilocybe and in 1958, Albert Hofmann first identified psilocin and psilocybin as the active compound in these mushrooms.
At present, hallucinogenic mushroom use has been reported among a number of groups spanning from central Mexico to Oaxaca, including groups of Nahua, Mixtecs, Mixe, Mazatecs, Zapotecs, and others.
The popularization of entheogens by Wasson, Timothy Leary, and others has led to an explosion in the use of hallucinogenic Psilocybe throughout the world. By the early 1970s, a number of psychoactive Psilocybe species were described from temperate North America, Europe, and Asia and were widely collected. Books describing methods of cultivating Psilocybe cubensis in large quantities were also published. The relatively easy availability of hallucinogenic Psilocybe from wild and cultivated sources has made it among the most widely used of the hallucinogenic drugs.
# Legal status
Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.[2] Schedule I drugs are drugs with a high potential for abuse that have no recognized medical uses. This status is reflected in the drug laws of the majority of the world's nations. Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there is a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places. The legal status of Psilocybe spores is even more ambiguous, as the spores contain neither psilocybin nor psilocin, and hence are not illegal to sell or possess in many jurisdictions, though many jurisdictions will prosecute under broader laws prohibiting items that are used in drug manufacture. A few jurisdictions (such as the US states of California, Georgia, and Idaho) have specifically prohibited the sale and possession of psilocybin mushroom spores. Cultivation of psilocybin mushrooms is considered drug manufacture in most jurisdictions and is often severely penalized, though some countries and one US state have ruled that growing psilocybin mushrooms does not qualify as "manufacturing" a controlled substance.
# Notable species
- Psilocybe cubensis, (= Stropharia cubensis); the most commonly grown and consumed Psilocybe, due to ease of cultivation and large size of carpophores; also commonly collected throughout the tropics and subtropics, including the US Gulf Coast; nicknamed the commercial psilocybe.
- Psilocybe semilanceata, found in northern temperate climates; nicknamed the liberty cap.
- Psilocybe cyanescens, native to the Pacific Northwest of North America, but also found in western Europe; nicknamed the wavy-cap or wavies.
- Psilocybe azurescens, a highly potent species native to Oregon, but popular in outdoor cultivation, and expanding its range as a result; nicknamed azies. | https://www.wikidoc.org/index.php/Psilocybe | |
5d4a1a04ad0f91a51155c149532c236471a412a6 | wikidoc | Pterygium | Pterygium
Synonyms and keywords: pterygia
# Overview
Pterygium usually refers to a benign growth of the conjunctiva. Alternately, it refers to any winglike triangular membrane occurring in the neck, eyelids, knees, elbows, ankles or digits. An example is popliteal pterygium syndrome, which affects the legs. The term comes from the Greek word pterygion meaning "wing". When associated with the conjunctiva, a pterygium commonly grows from the nasal side of the sclera. It is associated with, and thought to be caused by ultraviolet-light exposure (e.g. sunlight), low humidity, and dust. The predominance of pterygia on the nasal side is possibly a result of the sun's rays passing laterally through the cornea where it undergoes refraction and becomes focused on the limbic area. Sunlight passes unobstructed from the lateral side of the eye, focusing on the medial limbus after passing through the cornea. On the contralateral side, however, the shadow of the nose medially reduces the intensity of sunlight focused on the lateral/temporal limbus.
# Historical Perspective
It is not clear when pterygium first became known. However,
# Classification
Pterygium can be classified into 3 main groups:
# Pathophysiology
- Pterygium in the conjunctiva is characterized by elastic degeneration of collagen and fibrovascular proliferation.
- It has an advancing portion called the head of the pterygium, which is connected to the main body of the pterygium by the neck.
- Sometimes a line of iron deposition can be seen adjacent to the head of the pterygium called Stocker's line.
- The location of the line can give an indication of the pattern of growth.
- As it is a benign growth, it requires no treatment unless it grows to such an extent that it covers the pupil, obstructing vision.
# Causes
The exact cause is unknown, but it is associated with excessive exposure to wind, sun, or sand.
# Differentiating Pterygium From Other Diseases
- Pinguecula is a degenerative eye condition that is often confused with pterygium.
A pinguecula is a yellowish, slightly raised conjunctival lesion arising at the limbal conjunctiva.
Unlike a pterygium that arises from the limbus and progresses onto the cornea, a pinguecula arises from the limbus and remains confined to the conjunctiva without corneal involvement.
- A pinguecula is a yellowish, slightly raised conjunctival lesion arising at the limbal conjunctiva.
- Unlike a pterygium that arises from the limbus and progresses onto the cornea, a pinguecula arises from the limbus and remains confined to the conjunctiva without corneal involvement.
- Pseudopterygium
- Neoplasia
Carcinoma in situ
Squamous cell carcinoma
Other neoplastic diseases
- Carcinoma in situ
- Squamous cell carcinoma
- Other neoplastic diseases
# Epidemiology and Demographics
## Age
Several population-based studies have found higher rates of pterygium to be associated with older age.
It is uncommon for patients to present with pterygium prior to age 20 years. Patients older than 40 years have the highest prevalence of pterygia, while patients aged 20-40 years are reported to have the highest incidence of pterygium.
## Gender
Pterygium is reported to occur in males twice as frequently as in females.
## Race
# Risk Factors
Several risk factors may lead to the formation of pterygium, these include:
- Ultraviolet (UV) light
UV radiation may trigger events that produce damage to cellular DNA, RNA, and extracellular matrix composition
- UV radiation may trigger events that produce damage to cellular DNA, RNA, and extracellular matrix composition
- Abnormal conjunctival expression of tumor suppressor gene p53
- Angiogenesis-related factors
- Human papillomavirus (HPV) infection
- Abnormal human leukocyte antigen (HLA)expression
- Family history
# Screening
There is insufficient evidence to recommend routine screening for pterygium.
# Natural History, Complications, and Prognosis
### Natural History
- The natural history of pterygium is poorly understood.
- Pterygium, when active, can grow over a period of several months to years.
- Activity is marked clinically by redness and localized thickening, which probably represent active inflammation. When inactive (white and flat), pterygium may remain static for decades with no measurable increase in size or clinical significance. It is unclear how pterygium converts from active to inactive, or if it can be reactivated.
### Complications
Complications of pterygium include the following:
- Distortion and/or reduction of central vision
- Redness
- Irritation
- Chronic scarring of the conjunctiva and the cornea
### Prognosis
- Recurrence rates for simple surgical excision to bare sclera are high, varying between 30 to 80 percent of cases, and reported as high as 90 percent in certain subpopulations.
- The high recurrence rate, even when adjunctive measures are used with excision, is the main reason that surgery is not recommended for a small pterygium, for irritation, or for cosmetic reasons alone.
- The visual and cosmetic prognosis following pterygium excision is good. The procedures are well tolerated by patients, and, aside from some discomfort in the first few postoperative days, most patients are able to resume full activity within 48 hours of their surgery.
Those patients who develop recurrent pterygia can be retreated with repeat surgical excision and grafting, with conjunctival/limbal autografts or amniotic membrane transplants in selected patients.
- Those patients who develop recurrent pterygia can be retreated with repeat surgical excision and grafting, with conjunctival/limbal autografts or amniotic membrane transplants in selected patients.
# Diagnosis
## Diagnostic Study of Choice
- The diagnosis of pterygium is made by the classic clinical appearance of a wedge-shaped growth extending onto the cornea.
- However, pterygium does not always manifest in its classic form, and other conditions may have a similar appearance.
- It is important to distinguish pterygium from these other conditions, particularly neoplastic lesions.
## History and Symptoms
- The most common symptoms caused by pterygium are redness and irritation.
- Visual impairment is less common. In the absence of symptoms, patients may also report a change in the appearance of their eye, or pterygium may be noted incidentally on physical examination.
## Physical Examination
## Laboratory Findings
## Electrocardiogram
There are no ECG findings associated with pteryigum.
## X-ray
There are no x-ray findings associated with pteryigum.
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with pteryigum.
## CT scan
There are no CT scan findings associated with pteryigum.
## MRI
There are no MRI findings associated with pteryigum.
## Other Imaging Findings
Corneal topography can be very useful in determining the degree of irregular astigmatism induced by an advanced pterygium.
## Other Diagnostic Studies
# Treatment
## Medical Therapy
Medical treatments are for symptomatic relief and have not been shown to stop progression or cause regression of a pterygium.
- Patients with pterygium that do not affect vision or eye movement may be treated symptomatically with topical lubricants including drops, ointments, and gels, all of which are available over-the-counter.
Artificial tears are the most frequently utilized topical lubricant for pterygium and may help to reduce symptoms.
They can be given 1 to 2 drops to affected area three to four times daily.
Preservative-free preparations should be used in patients who have irritative symptoms with preservatives or who need to use lubrication more than four times per day.
Preservative-free preparations are more expensive.
- Artificial tears are the most frequently utilized topical lubricant for pterygium and may help to reduce symptoms.
- They can be given 1 to 2 drops to affected area three to four times daily.
- Preservative-free preparations should be used in patients who have irritative symptoms with preservatives or who need to use lubrication more than four times per day.
- Preservative-free preparations are more expensive.
- Treatment with topical decongestants, NSAIDs, and glucocorticoids may also be effective for symptomatic relief of pterygium.
These are associated with adverse effects which limit their use.
Topical decongestants can be used to treat redness and irritation not relieved by artificial tears.
- These are associated with adverse effects which limit their use.
- Topical decongestants can be used to treat redness and irritation not relieved by artificial tears.
## Surgery
Definitive treatment is achieved only by surgical removal. Long term follow up is required as pterygium may recur even after complete surgical correction.
Indications for surgical removal of pterygium include:
- Astigmatism leading to visual impairment
- Opacity in the visual axis
- Documented growth that is threatening to affect the visual axis via astigmatism or opacity
- Restriction of eye movement
- Significant cosmetic impact or intractable irritation
## Primary Prevention
- Theoretically, minimizing exposure to ultraviolet radiation should reduce the risk of development of pterygium in susceptible individuals.
- Patients are advised to use a hat or a cap with a brim, in addition to ultraviolet-blocking coatings on the lenses of glasses/sunglasses to be used in areas of sun exposure.
## Secondary Prevention | Pterygium
Template:DiseaseDisorder infobox
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2]
Synonyms and keywords: pterygia
# Overview
Pterygium usually refers to a benign growth of the conjunctiva. Alternately, it refers to any winglike triangular membrane occurring in the neck, eyelids, knees, elbows, ankles or digits. An example is popliteal pterygium syndrome, which affects the legs. The term comes from the Greek word pterygion meaning "wing". When associated with the conjunctiva, a pterygium commonly grows from the nasal side of the sclera. It is associated with, and thought to be caused by ultraviolet-light exposure (e.g. sunlight), low humidity, and dust. The predominance of pterygia on the nasal side is possibly a result of the sun's rays passing laterally through the cornea where it undergoes refraction and becomes focused on the limbic area. Sunlight passes unobstructed from the lateral side of the eye, focusing on the medial limbus after passing through the cornea. On the contralateral side, however, the shadow of the nose medially reduces the intensity of sunlight focused on the lateral/temporal limbus.
# Historical Perspective
It is not clear when pterygium first became known. However,
# Classification
Pterygium can be classified into 3 main groups:[1]
# Pathophysiology
- Pterygium in the conjunctiva is characterized by elastic degeneration of collagen and fibrovascular proliferation.
- It has an advancing portion called the head of the pterygium, which is connected to the main body of the pterygium by the neck.
- Sometimes a line of iron deposition can be seen adjacent to the head of the pterygium called Stocker's line.
- The location of the line can give an indication of the pattern of growth.
- As it is a benign growth, it requires no treatment unless it grows to such an extent that it covers the pupil, obstructing vision.
# Causes
The exact cause is unknown, but it is associated with excessive exposure to wind, sun, or sand.
# Differentiating Pterygium From Other Diseases
- Pinguecula is a degenerative eye condition that is often confused with pterygium.
A pinguecula is a yellowish, slightly raised conjunctival lesion arising at the limbal conjunctiva.
Unlike a pterygium that arises from the limbus and progresses onto the cornea, a pinguecula arises from the limbus and remains confined to the conjunctiva without corneal involvement.
- A pinguecula is a yellowish, slightly raised conjunctival lesion arising at the limbal conjunctiva.
- Unlike a pterygium that arises from the limbus and progresses onto the cornea, a pinguecula arises from the limbus and remains confined to the conjunctiva without corneal involvement.
- Pseudopterygium
- Neoplasia
Carcinoma in situ
Squamous cell carcinoma
Other neoplastic diseases
- Carcinoma in situ
- Squamous cell carcinoma
- Other neoplastic diseases
-
# Epidemiology and Demographics
## Age
Several population-based studies have found higher rates of pterygium to be associated with older age.
It is uncommon for patients to present with pterygium prior to age 20 years. Patients older than 40 years have the highest prevalence of pterygia, while patients aged 20-40 years are reported to have the highest incidence of pterygium.
## Gender
Pterygium is reported to occur in males twice as frequently as in females.
## Race
# Risk Factors
Several risk factors may lead to the formation of pterygium, these include:[2]
- Ultraviolet (UV) light[3]
UV radiation may trigger events that produce damage to cellular DNA, RNA, and extracellular matrix composition
- UV radiation may trigger events that produce damage to cellular DNA, RNA, and extracellular matrix composition
- Abnormal conjunctival expression of tumor suppressor gene p53
- Angiogenesis-related factors
- Human papillomavirus (HPV) infection
- Abnormal human leukocyte antigen (HLA)expression
- Family history
# Screening
There is insufficient evidence to recommend routine screening for pterygium.
# Natural History, Complications, and Prognosis
### Natural History
- The natural history of pterygium is poorly understood.
- Pterygium, when active, can grow over a period of several months to years.
- Activity is marked clinically by redness and localized thickening, which probably represent active inflammation. When inactive (white and flat), pterygium may remain static for decades with no measurable increase in size or clinical significance. It is unclear how pterygium converts from active to inactive, or if it can be reactivated.
### Complications
Complications of pterygium include the following:
- Distortion and/or reduction of central vision
- Redness
- Irritation
- Chronic scarring of the conjunctiva and the cornea
### Prognosis
- Recurrence rates for simple surgical excision to bare sclera are high, varying between 30 to 80 percent of cases, and reported as high as 90 percent in certain subpopulations.
- The high recurrence rate, even when adjunctive measures are used with excision, is the main reason that surgery is not recommended for a small pterygium, for irritation, or for cosmetic reasons alone.
- The visual and cosmetic prognosis following pterygium excision is good. The procedures are well tolerated by patients, and, aside from some discomfort in the first few postoperative days, most patients are able to resume full activity within 48 hours of their surgery.[4]
Those patients who develop recurrent pterygia can be retreated with repeat surgical excision and grafting, with conjunctival/limbal autografts or amniotic membrane transplants in selected patients.[5]
- Those patients who develop recurrent pterygia can be retreated with repeat surgical excision and grafting, with conjunctival/limbal autografts or amniotic membrane transplants in selected patients.[5]
# Diagnosis
## Diagnostic Study of Choice
- The diagnosis of pterygium is made by the classic clinical appearance of a wedge-shaped growth extending onto the cornea.
- However, pterygium does not always manifest in its classic form, and other conditions may have a similar appearance.
- It is important to distinguish pterygium from these other conditions, particularly neoplastic lesions.
## History and Symptoms
- The most common symptoms caused by pterygium are redness and irritation.
- Visual impairment is less common. In the absence of symptoms, patients may also report a change in the appearance of their eye, or pterygium may be noted incidentally on physical examination.
## Physical Examination
## Laboratory Findings
## Electrocardiogram
There are no ECG findings associated with pteryigum.
## X-ray
There are no x-ray findings associated with pteryigum.
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with pteryigum.
## CT scan
There are no CT scan findings associated with pteryigum.
## MRI
There are no MRI findings associated with pteryigum.
## Other Imaging Findings
Corneal topography can be very useful in determining the degree of irregular astigmatism induced by an advanced pterygium.
## Other Diagnostic Studies
# Treatment
## Medical Therapy
Medical treatments are for symptomatic relief and have not been shown to stop progression or cause regression of a pterygium.
- Patients with pterygium that do not affect vision or eye movement may be treated symptomatically with topical lubricants including drops, ointments, and gels, all of which are available over-the-counter.[6]
Artificial tears are the most frequently utilized topical lubricant for pterygium and may help to reduce symptoms.
They can be given 1 to 2 drops to affected area three to four times daily.
Preservative-free preparations should be used in patients who have irritative symptoms with preservatives or who need to use lubrication more than four times per day.
Preservative-free preparations are more expensive.
- Artificial tears are the most frequently utilized topical lubricant for pterygium and may help to reduce symptoms.
- They can be given 1 to 2 drops to affected area three to four times daily.
- Preservative-free preparations should be used in patients who have irritative symptoms with preservatives or who need to use lubrication more than four times per day.
- Preservative-free preparations are more expensive.
- Treatment with topical decongestants, NSAIDs, and glucocorticoids may also be effective for symptomatic relief of pterygium.[7][8]
These are associated with adverse effects which limit their use.
Topical decongestants can be used to treat redness and irritation not relieved by artificial tears.
- These are associated with adverse effects which limit their use.
- Topical decongestants can be used to treat redness and irritation not relieved by artificial tears.
## Surgery
Definitive treatment is achieved only by surgical removal. Long term follow up is required as pterygium may recur even after complete surgical correction.
Indications for surgical removal of pterygium include:
- Astigmatism leading to visual impairment
- Opacity in the visual axis
- Documented growth that is threatening to affect the visual axis via astigmatism or opacity
- Restriction of eye movement
- Significant cosmetic impact or intractable irritation
## Primary Prevention
- Theoretically, minimizing exposure to ultraviolet radiation should reduce the risk of development of pterygium in susceptible individuals.
- Patients are advised to use a hat or a cap with a brim, in addition to ultraviolet-blocking coatings on the lenses of glasses/sunglasses to be used in areas of sun exposure.
## Secondary Prevention | https://www.wikidoc.org/index.php/Pterygia | |
af47e1700005dcdab76a90d56d8b5576a6cc8907 | wikidoc | Pulmonate | Pulmonate
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
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The Pulmonata or "pulmonates" are an order (once a subclass) of snails and slugs that have developed a pallial lung and thus can breathe air. The group includes many land and freshwater families and a few marine ones.
Pulmonata are known from the Carboniferous to the recent periods.
# Taxonomy
Order Pulmonata Cuvier in Blainville, 1814 (pulmonates)
- Suborder Systellommatophora Pilsbry, 1948
Superfamily Onchidioidea Rafinesque, 1815
Superfamily Otinoidea H. & A. Adams, 1855
Superfamily Rathouisioidea Sarasin, 1889
- Superfamily Onchidioidea Rafinesque, 1815
Superfamily Otinoidea H. & A. Adams, 1855
Superfamily Rathouisioidea Sarasin, 1889
- Superfamily Onchidioidea Rafinesque, 1815
- Superfamily Otinoidea H. & A. Adams, 1855
- Superfamily Rathouisioidea Sarasin, 1889
- Suborder Basommatophora Keferstein in Bronn, 1864 (freshwater pulmonates, pond snails)
Superfamily Acroloxoidea Thiele, 1931
Superfamily Amphiboloidea J.E. Gray, 1840
Superfamily Chilinoidea H. & A. Adams, 1855
Superfamily Glacidorboidea Ponder, 1986
Superfamily Lymnaeoidea Rafinesque, 1815
Superfamily Planorboidea Rafinesque, 1815
Superfamily Siphonarioidea J.E. Gray, 1840
- Superfamily Acroloxoidea Thiele, 1931
Superfamily Amphiboloidea J.E. Gray, 1840
Superfamily Chilinoidea H. & A. Adams, 1855
Superfamily Glacidorboidea Ponder, 1986
Superfamily Lymnaeoidea Rafinesque, 1815
Superfamily Planorboidea Rafinesque, 1815
Superfamily Siphonarioidea J.E. Gray, 1840
- Superfamily Acroloxoidea Thiele, 1931
- Superfamily Amphiboloidea J.E. Gray, 1840
- Superfamily Chilinoidea H. & A. Adams, 1855
- Superfamily Glacidorboidea Ponder, 1986
- Superfamily Lymnaeoidea Rafinesque, 1815
- Superfamily Planorboidea Rafinesque, 1815
- Superfamily Siphonarioidea J.E. Gray, 1840
- Suborder Eupulmonata Haszprunar & Huber, 1990
Infraorder Acteophila Dall, 1885 (= formerly Archaeopulmonata)
Superfamily Melampoidea Stimpson, 1851
Infraorder Trimusculiformes Minichev & Starobogatov, 1975
Superfamily Trimusculoidea Zilch, 1959
- Infraorder Acteophila Dall, 1885 (= formerly Archaeopulmonata)
Superfamily Melampoidea Stimpson, 1851
- Superfamily Melampoidea Stimpson, 1851
- Infraorder Trimusculiformes Minichev & Starobogatov, 1975
Superfamily Trimusculoidea Zilch, 1959
- Superfamily Trimusculoidea Zilch, 1959
- Infraorder Stylommatophora A. Schmidt, 1856 (land snails)
Subinfraorder Orthurethra
Superfamily Achatinelloidea Gulick, 1873
Superfamily Cochlicopoidea Pilsbry, 1900
Superfamily Partuloidea Pilsbry, 1900
Superfamily Pupilloidea Turton, 1831
Subinfraorder Sigmurethra
Superfamily Acavoidea Pilsbry, 1895
Superfamily Achatinoidea Swainson, 1840
Superfamily Aillyoidea Baker, 1960
Superfamily Arionoidea J.E. Gray in Turnton, 1840
Superfamily Buliminoidea Clessin, 1879
Superfamily Camaenoidea Pilsbry, 1895
Superfamily Clausilioidea Mörch, 1864
Superfamily Dyakioidea Gude & Woodward, 1921
Superfamily Gastrodontoidea Tryon, 1866
Superfamily Helicoidea Rafinesque, 1815
Superfamily Helixarionoidea Bourguignat, 1877
Superfamily Limacoidea Rafinesque, 1815
Superfamily Oleacinoidea H. & A. Adams, 1855
Superfamily Orthalicoidea Albers-Martens, 1860
Superfamily Plectopylidoidea Moellendorf, 1900
Superfamily Polygyroidea Pilsbry, 1894
Superfamily Punctoidea Morse, 1864
Superfamily Rhytidoidea Pilsbry, 1893
Superfamily Sagdidoidera Pilsbry, 1895
Superfamily Staffordioidea Thiele, 1931
Superfamily Streptaxoidea J.E. Gray, 1806
Superfamily Strophocheiloidea Thiele, 1926
Superfamily Trigonochlamydoidea Hese, 1882
Superfamily Zonitoidea Mörch, 1864
? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
? Superfamily Succineoidea Beck, 1837 (= Heterurethra)
- Infraorder Stylommatophora A. Schmidt, 1856 (land snails)
Subinfraorder Orthurethra
Superfamily Achatinelloidea Gulick, 1873
Superfamily Cochlicopoidea Pilsbry, 1900
Superfamily Partuloidea Pilsbry, 1900
Superfamily Pupilloidea Turton, 1831
Subinfraorder Sigmurethra
Superfamily Acavoidea Pilsbry, 1895
Superfamily Achatinoidea Swainson, 1840
Superfamily Aillyoidea Baker, 1960
Superfamily Arionoidea J.E. Gray in Turnton, 1840
Superfamily Buliminoidea Clessin, 1879
Superfamily Camaenoidea Pilsbry, 1895
Superfamily Clausilioidea Mörch, 1864
Superfamily Dyakioidea Gude & Woodward, 1921
Superfamily Gastrodontoidea Tryon, 1866
Superfamily Helicoidea Rafinesque, 1815
Superfamily Helixarionoidea Bourguignat, 1877
Superfamily Limacoidea Rafinesque, 1815
Superfamily Oleacinoidea H. & A. Adams, 1855
Superfamily Orthalicoidea Albers-Martens, 1860
Superfamily Plectopylidoidea Moellendorf, 1900
Superfamily Polygyroidea Pilsbry, 1894
Superfamily Punctoidea Morse, 1864
Superfamily Rhytidoidea Pilsbry, 1893
Superfamily Sagdidoidera Pilsbry, 1895
Superfamily Staffordioidea Thiele, 1931
Superfamily Streptaxoidea J.E. Gray, 1806
Superfamily Strophocheiloidea Thiele, 1926
Superfamily Trigonochlamydoidea Hese, 1882
Superfamily Zonitoidea Mörch, 1864
? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
? Superfamily Succineoidea Beck, 1837 (= Heterurethra)
- Subinfraorder Orthurethra
- Superfamily Achatinelloidea Gulick, 1873
- Superfamily Cochlicopoidea Pilsbry, 1900
- Superfamily Partuloidea Pilsbry, 1900
- Superfamily Pupilloidea Turton, 1831
- Subinfraorder Sigmurethra
- Superfamily Acavoidea Pilsbry, 1895
- Superfamily Achatinoidea Swainson, 1840
- Superfamily Aillyoidea Baker, 1960
- Superfamily Arionoidea J.E. Gray in Turnton, 1840
- Superfamily Buliminoidea Clessin, 1879
- Superfamily Camaenoidea Pilsbry, 1895
- Superfamily Clausilioidea Mörch, 1864
- Superfamily Dyakioidea Gude & Woodward, 1921
- Superfamily Gastrodontoidea Tryon, 1866
- Superfamily Helicoidea Rafinesque, 1815
- Superfamily Helixarionoidea Bourguignat, 1877
- Superfamily Limacoidea Rafinesque, 1815
- Superfamily Oleacinoidea H. & A. Adams, 1855
- Superfamily Orthalicoidea Albers-Martens, 1860
- Superfamily Plectopylidoidea Moellendorf, 1900
- Superfamily Polygyroidea Pilsbry, 1894
- Superfamily Punctoidea Morse, 1864
- Superfamily Rhytidoidea Pilsbry, 1893
- Superfamily Sagdidoidera Pilsbry, 1895
- Superfamily Staffordioidea Thiele, 1931
- Superfamily Streptaxoidea J.E. Gray, 1806
- Superfamily Strophocheiloidea Thiele, 1926
- Superfamily Trigonochlamydoidea Hese, 1882
- Superfamily Zonitoidea Mörch, 1864
- ? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
- ? Superfamily Succineoidea Beck, 1837 (= Heterurethra) | Pulmonate
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
The Pulmonata or "pulmonates" are an order (once a subclass) of snails and slugs that have developed a pallial lung and thus can breathe air. The group includes many land and freshwater families and a few marine ones.
Pulmonata are known from the Carboniferous to the recent periods.[1]
# Taxonomy
Order Pulmonata Cuvier in Blainville, 1814 (pulmonates)
- Suborder Systellommatophora Pilsbry, 1948
Superfamily Onchidioidea Rafinesque, 1815
Superfamily Otinoidea H. & A. Adams, 1855
Superfamily Rathouisioidea Sarasin, 1889
- Superfamily Onchidioidea Rafinesque, 1815
Superfamily Otinoidea H. & A. Adams, 1855
Superfamily Rathouisioidea Sarasin, 1889
- Superfamily Onchidioidea Rafinesque, 1815
- Superfamily Otinoidea H. & A. Adams, 1855
- Superfamily Rathouisioidea Sarasin, 1889
- Suborder Basommatophora Keferstein in Bronn, 1864 (freshwater pulmonates, pond snails)
Superfamily Acroloxoidea Thiele, 1931
Superfamily Amphiboloidea J.E. Gray, 1840
Superfamily Chilinoidea H. & A. Adams, 1855
Superfamily Glacidorboidea Ponder, 1986
Superfamily Lymnaeoidea Rafinesque, 1815
Superfamily Planorboidea Rafinesque, 1815
Superfamily Siphonarioidea J.E. Gray, 1840
- Superfamily Acroloxoidea Thiele, 1931
Superfamily Amphiboloidea J.E. Gray, 1840
Superfamily Chilinoidea H. & A. Adams, 1855
Superfamily Glacidorboidea Ponder, 1986
Superfamily Lymnaeoidea Rafinesque, 1815
Superfamily Planorboidea Rafinesque, 1815
Superfamily Siphonarioidea J.E. Gray, 1840
- Superfamily Acroloxoidea Thiele, 1931
- Superfamily Amphiboloidea J.E. Gray, 1840
- Superfamily Chilinoidea H. & A. Adams, 1855
- Superfamily Glacidorboidea Ponder, 1986
- Superfamily Lymnaeoidea Rafinesque, 1815
- Superfamily Planorboidea Rafinesque, 1815
- Superfamily Siphonarioidea J.E. Gray, 1840
- Suborder Eupulmonata Haszprunar & Huber, 1990
Infraorder Acteophila Dall, 1885 (= formerly Archaeopulmonata)
Superfamily Melampoidea Stimpson, 1851
Infraorder Trimusculiformes Minichev & Starobogatov, 1975
Superfamily Trimusculoidea Zilch, 1959
- Infraorder Acteophila Dall, 1885 (= formerly Archaeopulmonata)
Superfamily Melampoidea Stimpson, 1851
- Superfamily Melampoidea Stimpson, 1851
- Infraorder Trimusculiformes Minichev & Starobogatov, 1975
Superfamily Trimusculoidea Zilch, 1959
- Superfamily Trimusculoidea Zilch, 1959
- Infraorder Stylommatophora A. Schmidt, 1856 (land snails)
Subinfraorder Orthurethra
Superfamily Achatinelloidea Gulick, 1873
Superfamily Cochlicopoidea Pilsbry, 1900
Superfamily Partuloidea Pilsbry, 1900
Superfamily Pupilloidea Turton, 1831
Subinfraorder Sigmurethra
Superfamily Acavoidea Pilsbry, 1895
Superfamily Achatinoidea Swainson, 1840
Superfamily Aillyoidea Baker, 1960
Superfamily Arionoidea J.E. Gray in Turnton, 1840
Superfamily Buliminoidea Clessin, 1879
Superfamily Camaenoidea Pilsbry, 1895
Superfamily Clausilioidea Mörch, 1864
Superfamily Dyakioidea Gude & Woodward, 1921
Superfamily Gastrodontoidea Tryon, 1866
Superfamily Helicoidea Rafinesque, 1815
Superfamily Helixarionoidea Bourguignat, 1877
Superfamily Limacoidea Rafinesque, 1815
Superfamily Oleacinoidea H. & A. Adams, 1855
Superfamily Orthalicoidea Albers-Martens, 1860
Superfamily Plectopylidoidea Moellendorf, 1900
Superfamily Polygyroidea Pilsbry, 1894
Superfamily Punctoidea Morse, 1864
Superfamily Rhytidoidea Pilsbry, 1893
Superfamily Sagdidoidera Pilsbry, 1895
Superfamily Staffordioidea Thiele, 1931
Superfamily Streptaxoidea J.E. Gray, 1806
Superfamily Strophocheiloidea Thiele, 1926
Superfamily Trigonochlamydoidea Hese, 1882
Superfamily Zonitoidea Mörch, 1864
? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
? Superfamily Succineoidea Beck, 1837 (= Heterurethra)
- Infraorder Stylommatophora A. Schmidt, 1856 (land snails)
Subinfraorder Orthurethra
Superfamily Achatinelloidea Gulick, 1873
Superfamily Cochlicopoidea Pilsbry, 1900
Superfamily Partuloidea Pilsbry, 1900
Superfamily Pupilloidea Turton, 1831
Subinfraorder Sigmurethra
Superfamily Acavoidea Pilsbry, 1895
Superfamily Achatinoidea Swainson, 1840
Superfamily Aillyoidea Baker, 1960
Superfamily Arionoidea J.E. Gray in Turnton, 1840
Superfamily Buliminoidea Clessin, 1879
Superfamily Camaenoidea Pilsbry, 1895
Superfamily Clausilioidea Mörch, 1864
Superfamily Dyakioidea Gude & Woodward, 1921
Superfamily Gastrodontoidea Tryon, 1866
Superfamily Helicoidea Rafinesque, 1815
Superfamily Helixarionoidea Bourguignat, 1877
Superfamily Limacoidea Rafinesque, 1815
Superfamily Oleacinoidea H. & A. Adams, 1855
Superfamily Orthalicoidea Albers-Martens, 1860
Superfamily Plectopylidoidea Moellendorf, 1900
Superfamily Polygyroidea Pilsbry, 1894
Superfamily Punctoidea Morse, 1864
Superfamily Rhytidoidea Pilsbry, 1893
Superfamily Sagdidoidera Pilsbry, 1895
Superfamily Staffordioidea Thiele, 1931
Superfamily Streptaxoidea J.E. Gray, 1806
Superfamily Strophocheiloidea Thiele, 1926
Superfamily Trigonochlamydoidea Hese, 1882
Superfamily Zonitoidea Mörch, 1864
? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
? Superfamily Succineoidea Beck, 1837 (= Heterurethra)
- Subinfraorder Orthurethra
- Superfamily Achatinelloidea Gulick, 1873
- Superfamily Cochlicopoidea Pilsbry, 1900
- Superfamily Partuloidea Pilsbry, 1900
- Superfamily Pupilloidea Turton, 1831
- Subinfraorder Sigmurethra
- Superfamily Acavoidea Pilsbry, 1895
- Superfamily Achatinoidea Swainson, 1840
- Superfamily Aillyoidea Baker, 1960
- Superfamily Arionoidea J.E. Gray in Turnton, 1840
- Superfamily Buliminoidea Clessin, 1879
- Superfamily Camaenoidea Pilsbry, 1895
- Superfamily Clausilioidea Mörch, 1864
- Superfamily Dyakioidea Gude & Woodward, 1921
- Superfamily Gastrodontoidea Tryon, 1866
- Superfamily Helicoidea Rafinesque, 1815
- Superfamily Helixarionoidea Bourguignat, 1877
- Superfamily Limacoidea Rafinesque, 1815
- Superfamily Oleacinoidea H. & A. Adams, 1855
- Superfamily Orthalicoidea Albers-Martens, 1860
- Superfamily Plectopylidoidea Moellendorf, 1900
- Superfamily Polygyroidea Pilsbry, 1894
- Superfamily Punctoidea Morse, 1864
- Superfamily Rhytidoidea Pilsbry, 1893
- Superfamily Sagdidoidera Pilsbry, 1895
- Superfamily Staffordioidea Thiele, 1931
- Superfamily Streptaxoidea J.E. Gray, 1806
- Superfamily Strophocheiloidea Thiele, 1926
- Superfamily Trigonochlamydoidea Hese, 1882
- Superfamily Zonitoidea Mörch, 1864
- ? Superfamily Athoracophoroidea P. Fischer, 1883 (= Tracheopulmonata)
- ? Superfamily Succineoidea Beck, 1837 (= Heterurethra) | https://www.wikidoc.org/index.php/Pulmonate | |
d79d6b827ecd64bfb6389f4a83ce26b2f6b7209b | wikidoc | Puromycin | Puromycin
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
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Puromycin is an antibiotic that is a potent inhibitor of translation.
# Inhibition of translation
Puromycin is an aminonucleoside antibiotic, derived from the Streptomyces alboniger bacterium, that causes premature chain termination during translation taking place in the ribosome. Part of the molecule resembles the 3' end of the aminoacylated tRNA. It will enter the A site and transfer to the growing chain, causing premature chain release. The exact mechanism of action is unknown at this time, but, the 3' position contains an amide linkage instead of the normal ester linkage of tRNA, the amide bond makes the molecule much more resistant to hydrolysis and thus causes the ribosome to become stopped.
It is not selective for either prokaryotes or eukaryotes.
Also of note, puromycin is critical in mRNA display as it allows the growing peptide chain to be covalently bonded to its own mRNA template. | Puromycin
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 [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Puromycin is an antibiotic that is a potent inhibitor of translation.
# Inhibition of translation
Puromycin is an aminonucleoside antibiotic, derived from the Streptomyces alboniger bacterium, that causes premature chain termination during translation taking place in the ribosome. Part of the molecule resembles the 3' end of the aminoacylated tRNA. It will enter the A site and transfer to the growing chain, causing premature chain release. The exact mechanism of action is unknown at this time, but, the 3' position contains an amide linkage instead of the normal ester linkage of tRNA, the amide bond makes the molecule much more resistant to hydrolysis and thus causes the ribosome to become stopped.
It is not selective for either prokaryotes or eukaryotes.
Also of note, puromycin is critical in mRNA display as it allows the growing peptide chain to be covalently bonded to its own mRNA template.
# External links
- Puromycin from Fermentek
Template:SIB
de:Puromycin
sl:Puromicin
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Puromycin | |
a8d0f47ed466088ff5998170cee7927b3662081a | wikidoc | Pyritinol | Pyritinol
# Overview
Pyritinol also called pyridoxine disulfide or pyrithioxine (European drug names Encephabol, Encefabol, Cerbon 6) is a semi-natural water soluble analog of vitamin B6 (Pyridoxine HCl). It was produced in 1961 by Merck Laboratories by bonding 2 vitamin B6 compounds (pyridoxine) together with a disulfide bridge. Since the 1970s, it has been a prescription and OTC drug in several countries for cognitive disorders and learning disorders in children. Since the early 1990s it has been sold as a nootropic dietary supplement in the United States.
It is approved for "symptomatic treatment of chronically impaired brain function in dementia syndromes" and for "supportive treatment of sequelae of craniocerebral trauma" in various European countries, including Austria, Germany, France, Italy, Portugal, and Greece.
In France it is also approved for rheumatoid arthritis as a disease modifying drug, on the basis of the results of clinical trials.
It is not licensed for use in the United Kingdom, but in many countries it is available over the counter and is widely advertised on the internet as being for "memory disturbances." From the known sales data, it is estimated that more than 100 000 individuals in European Union countries have taken pyritinol in the past five years.
One small study, with 12 subjects given pyritinol, showed an improvement in performance on tests of reaction time, but not on memory tests.
Some studies have found large doses of Pyritinol can help to reduce hangovers.
Common dosages are 100-1,600 mg daily, taken in 1-3 doses during the day.
# Adverse effects
Adverse effects include nausea, headache, and rarely allergic reaction. A 2004 survey of six case reports suggested a link between pyritinol and severe cholestatic hepatitis when on several drugs for certain diseases.
Other rare side effects: acute pancreatitis and photoallergic eruption. | Pyritinol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pyritinol also called pyridoxine disulfide or pyrithioxine (European drug names Encephabol, Encefabol, Cerbon 6) is a semi-natural water soluble analog of vitamin B6 (Pyridoxine HCl). It was produced in 1961 by Merck Laboratories by bonding 2 vitamin B6 compounds (pyridoxine) together with a disulfide bridge. Since the 1970s, it has been a prescription and OTC drug in several countries for cognitive disorders and learning disorders in children. Since the early 1990s it has been sold as a nootropic dietary supplement in the United States.
It is approved for "symptomatic treatment of chronically impaired brain function in dementia syndromes" and for "supportive treatment of sequelae of craniocerebral trauma" in various European countries, including Austria, Germany, France, Italy, Portugal, and Greece.
In France it is also approved for rheumatoid arthritis as a disease modifying drug, on the basis of the results of clinical trials.
It is not licensed for use in the United Kingdom, but in many countries it is available over the counter and is widely advertised on the internet as being for "memory disturbances." From the known sales data, it is estimated that more than 100 000 individuals in European Union countries have taken pyritinol in the past five years.
One small study, with 12 subjects given pyritinol, showed an improvement in performance on tests of reaction time, but not on memory tests.[1]
Some studies have found large doses of Pyritinol can help to reduce hangovers.[2]
Common dosages are 100-1,600 mg daily, taken in 1-3 doses during the day.
# Adverse effects
Adverse effects include nausea, headache, and rarely allergic reaction.[citation needed] A 2004 survey of six case reports suggested a link between pyritinol and severe cholestatic hepatitis when on several drugs for certain diseases.[3]
Other rare side effects: acute pancreatitis[4] and photoallergic eruption.[5] | https://www.wikidoc.org/index.php/Pyritinol | |
9407abbf3b40f511f4dff25f30aa5654b927f478 | wikidoc | Pyrvinium | Pyrvinium
# Overview
Pyrvinium is an anthelmintic effective for pinworms. Several forms of pyrvinium have been prepared with variable counter anions, such as halides, tosylate, triflate and pamoate.
Pyrvinium salts can also inhibit the growth of cancer cells. More specifically, the pamoate salt has been shown to have preferential toxicity for various cancer cell lines during glucose starvation.
# Synthesis
One synthetic method is based on Skraup synthesis and Paal-Knorr synthesis. More recently, an alternative convergent, synthetic strategy to pyrvinium triflate salts through Friedländer synthesis was reported. | Pyrvinium
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pyrvinium is an anthelmintic effective for pinworms.[1] Several forms of pyrvinium have been prepared with variable counter anions, such as halides, tosylate, triflate and pamoate.[2][3]
Pyrvinium salts can also inhibit the growth of cancer cells.[4] More specifically, the pamoate salt has been shown to have preferential toxicity for various cancer cell lines during glucose starvation.[5]
# Synthesis
One synthetic method is based on Skraup synthesis and Paal-Knorr synthesis.[4] More recently, an alternative convergent, synthetic strategy to pyrvinium triflate salts through Friedländer synthesis was reported.[3] | https://www.wikidoc.org/index.php/Pyrvinium | |
ad753a1c6cc10ff97c17e1cb2f7e16afef3cbe38 | wikidoc | Quercetin | Quercetin
# Overview
Quercetin is a flavonoid and more specifically a flavonol. It is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin found in citrus fruit. Quercetin is found to be the most active of the flavonoids in studies, and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. For example, it inhibits both the manufacture and release of histamine and other allergic/inflammatory mediators. In addition, it exerts potent antioxidant activity and vitamin C-sparing action.
Quercetin forms the glycosides quercitrin and rutin together with rhamnose and rutinose respectively.
Quercetin also shows anti-tumour properties. A study in the British Journal of Cancer showed that when treated with a combination of quercetin and ultrasound at 20 kHz for 1 minute duration, skin and prostate cancers show a 90% mortality within 48 hours with no visible mortality of normal cells. Note that ultrasound also promotes topical absorption by up to 1,000 times making the use of topical quercetin and ultrasound wands an interesting proposition.
Quercetin may have positive effects in combating or helping to prevent cancer, prostatitis, heart disease, cataracts, allergies/inflammations, and respiratory diseases such as bronchitis and asthma.
Foods rich in quercetin include capers (1800mg/kg), lovage (1700mg/kg), apples, tea (Camellia sinensis), onions (higher concentrations of quercetin occur in the outermost rings), red grapes, citrus fruits, broccoli and other leafy green vegetables, cherries, and a number of berries including raspberry, bog whortleberry (158 mg/kg, fresh weight), lingonberry (cultivated 74mg/kg, wild 146 mg/kg), cranberry (cultivated 83 mg/kg, wild 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), crowberry (cultivated 53mg/kg, wild 56 mg/kg), and the fruit of the prickly pear cactus. A recent study found that organically grown tomatoes had 79% more quercetin than conventionally grown.
A study by the University of Queensland, Australia, has also indicated the presence of quercetin in varieties of honey, including honey derived from eucalyptus and tea tree flowers.
In plants, it is a naturally-occurring polar auxin transport inhibitor.
Recent studies have supported that quercetin can help men with chronic prostatitis, possibly because of its action as a mast cell inhibitor. | Quercetin
Template:Chembox new
# Overview
Quercetin is a flavonoid and more specifically a flavonol. It is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin found in citrus fruit. Quercetin is found to be the most active of the flavonoids in studies,[citation needed] and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. For example, it inhibits both the manufacture and release of histamine and other allergic/inflammatory mediators. In addition, it exerts potent antioxidant activity and vitamin C-sparing action[citation needed].
Quercetin forms the glycosides quercitrin and rutin together with rhamnose and rutinose respectively.
Quercetin also shows anti-tumour properties. A study in the British Journal of Cancer showed that when treated with a combination of quercetin and ultrasound at 20 kHz for 1 minute duration, skin and prostate cancers show a 90% mortality within 48 hours with no visible mortality of normal cells.[1] Note that ultrasound also promotes topical absorption by up to 1,000 times making the use of topical quercetin and ultrasound wands an interesting proposition.
Quercetin may have positive effects in combating or helping to prevent cancer, prostatitis, heart disease, cataracts, allergies/inflammations, and respiratory diseases such as bronchitis and asthma.
Foods rich in quercetin include capers (1800mg/kg)[2], lovage (1700mg/kg), apples, tea (Camellia sinensis), onions (higher concentrations of quercetin occur in the outermost rings[3]), red grapes, citrus fruits, broccoli and other leafy green vegetables, cherries, and a number of berries including raspberry, bog whortleberry (158 mg/kg, fresh weight), lingonberry (cultivated 74mg/kg, wild 146 mg/kg), cranberry (cultivated 83 mg/kg, wild 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), crowberry (cultivated 53mg/kg, wild 56 mg/kg),[4] and the fruit of the prickly pear cactus. A recent study found that organically grown tomatoes had 79% more quercetin than conventionally grown.[5]
A study[6] by the University of Queensland, Australia, has also indicated the presence of quercetin in varieties of honey, including honey derived from eucalyptus and tea tree flowers.[7]
In plants, it is a naturally-occurring polar auxin transport inhibitor.
Recent studies have supported that quercetin can help men with chronic prostatitis, possibly because of its action as a mast cell inhibitor.[8] | https://www.wikidoc.org/index.php/Quercetin | |
078dd03a9b11393e931743e3fcd334ae0c63fabf | wikidoc | Quinoline | Quinoline
# Overview
Quinoline, also known as 1-azanaphthalene, 1-benzazine, or benzopyridine, is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a colourless hygroscopic liquid with a strong odour.
As it ages, if exposed to light, the liquid tends to become yellow and later brown. It is only slightly soluble in water but dissolves readily in many organic solvents.
Quinoline is an intermediate in metallurgical processes and in dye, polymer, and agrochemical production. It is also a preservative, disinfectant, and solvent.
It is toxic: short-term exposure to the vapour causes irritation of the nose, eyes, and throat as well as dizziness and nausea. Longer-term effects are uncertain, but quinoline has been linked to liver damage.
# Isolation and synthesis
Quinoline is naturally found in coal tar and was first extracted from this source in 1834 by F. Runge. It can be prepared using various methods:
- Combes quinoline synthesis using anilines and β-diketones.
- Conrad-Limpach synthesis using anilines and β-ketoesters.
- Doebner-Miller reaction using anilines and α,β-unsaturated carbonyl compounds.
- Friedländer synthesis using 2-aminobenzaldehyde and acetaldehyde.
- Skraup synthesis using ferrous sulfate, glycerol, aniline, nitrobenzene, and sulfuric acid.
- Povarov reaction using an aniline, a benzaldehyde and an activated alkene.
- Camps quinoline synthesis utilizing an o-acylaminoacetophenone and hydroxide | Quinoline
Template:Chembox new
# Overview
Quinoline, also known as 1-azanaphthalene, 1-benzazine, or benzo[b]pyridine, is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a colourless hygroscopic liquid with a strong odour.
As it ages, if exposed to light, the liquid tends to become yellow and later brown. It is only slightly soluble in water but dissolves readily in many organic solvents.
Quinoline is an intermediate in metallurgical processes and in dye, polymer, and agrochemical production. It is also a preservative, disinfectant, and solvent.
It is toxic: short-term exposure to the vapour causes irritation of the nose, eyes, and throat as well as dizziness and nausea. Longer-term effects are uncertain, but quinoline has been linked to liver damage.
# Isolation and synthesis
Quinoline is naturally found in coal tar and was first extracted from this source in 1834 by F. Runge. It can be prepared using various methods:
- Combes quinoline synthesis using anilines and β-diketones.
- Conrad-Limpach synthesis using anilines and β-ketoesters.
- Doebner-Miller reaction using anilines and α,β-unsaturated carbonyl compounds.
- Friedländer synthesis using 2-aminobenzaldehyde and acetaldehyde.
- Skraup synthesis using ferrous sulfate, glycerol, aniline, nitrobenzene, and sulfuric acid.
- Povarov reaction using an aniline, a benzaldehyde and an activated alkene.
- Camps quinoline synthesis utilizing an o-acylaminoacetophenone and hydroxide | https://www.wikidoc.org/index.php/Quinoline | |
ddce777d0b0d81f7fa0ffe75ae3ac894cfd95ceb | wikidoc | R-process | R-process
The r-process is a nucleosynthesis process occurring in core-collapse supernovae (see also supernova nucleosynthesis) responsible for the creation of approximately half of the neutron-rich atomic nuclei that are heavier than iron. The process entails a succession of rapid neutron captures on iron seed nuclei, hence the name r-process. The other predominate mechanism for the production of heavy elements is the s-process, which is nucleosynthesis by means of slow neutron captures, primarily occurring in AGB stars, and together these two processes account for a majority of galactic chemical evolution of elements heavier than iron.
# History
The r-process was seen to be needed from the relative abundances of isotopes of heavy elements and from a newly published table of abundances by Hans Suess and Harold Urey in 1956. Among other things, this data showed abundance peaks for Germanium, Xenon, and Platinum. According to quantum mechanics and the nuclear shell model, radioactive nuclei that decay into isotopes of these elements have closed neutron shells near the neutron drip line. This implies that some abundant nuclei must be created by rapid neutron capture, and it was only a matter of determining what other nuclei could be accounted for by such a process. A table apportioning the heavy isotopes between s-process and r-process was published in a famous review paper in 1957, which proposed the theory of stellar nucleosynthesis and set the frame-work for contemporary nuclear astrophysics.
# Nuclear physics
Immediately after a core-collapse supernova, there is an extremely high neutron flux (on the order of 1022 neutrons per cm² per second) and temperature, so that neutron captures occur much faster than beta-minus decays far from stability, meaning that the r-process "runs up" along the neutron drip line. The only two hold-ups inhibiting this process of climbing the neutron drip line are a notable decreases in the neutron-capture cross section at nuclei with closed neutron shells, and the degree of nuclear stability in the heavy-isotope region, which terminates the r-process when such nuclei become readily unstable to spontaneous fission (currently believed to be in the neutron-rich region near A = 270 (number of nucleons) in the chart of nuclides). After the neutron flux decreases, these highly unstable radioactive nuclei quickly decay to form stable, neutron-rich nuclei. So, while the s-process creates an abundance of stable nuclei with closed neutron shells, the r-process creates an abundance of nuclei about 10 Atomic mass units below the s-process peaks, as the r-process nuclei decay back towards stability on a constant A line in the chart of nuclides.
# Astrophysical sites
The most widely believed candidate site for the r-process are core-collapse supernovae (spectral Type Ib, Ic and II), which provide the necessary physical conditions for the R-process. However, the abundance of r-process nuclei requires that either only a small fraction of supernovae eject r-process nuclei to the interstellar medium, or that each supernova ejects only a very small amount of r-process material. A recently proposed alternative solution is that neutron star mergers (a binary star system of two neutron stars that collide) may also play a role in the production of r-process nuclei, but this has yet to be observationally confirmed. | R-process
The r-process is a nucleosynthesis process occurring in core-collapse supernovae (see also supernova nucleosynthesis) responsible for the creation of approximately half of the neutron-rich atomic nuclei that are heavier than iron. The process entails a succession of rapid neutron captures on iron seed nuclei, hence the name r-process. The other predominate mechanism for the production of heavy elements is the s-process, which is nucleosynthesis by means of slow neutron captures, primarily occurring in AGB stars, and together these two processes account for a majority of galactic chemical evolution of elements heavier than iron.
# History
The r-process was seen to be needed from the relative abundances of isotopes of heavy elements and from a newly published table of abundances by Hans Suess and Harold Urey in 1956. Among other things, this data showed abundance peaks for Germanium, Xenon, and Platinum. According to quantum mechanics and the nuclear shell model, radioactive nuclei that decay into isotopes of these elements have closed neutron shells near the neutron drip line. This implies that some abundant nuclei must be created by rapid neutron capture, and it was only a matter of determining what other nuclei could be accounted for by such a process. A table apportioning the heavy isotopes between s-process and r-process was published in a famous review paper in 1957[1], which proposed the theory of stellar nucleosynthesis and set the frame-work for contemporary nuclear astrophysics.
# Nuclear physics
Immediately after a core-collapse supernova, there is an extremely high neutron flux (on the order of 1022 neutrons per cm² per second) and temperature, so that neutron captures occur much faster than beta-minus decays far from stability, meaning that the r-process "runs up" along the neutron drip line. The only two hold-ups inhibiting this process of climbing the neutron drip line are a notable decreases in the neutron-capture cross section at nuclei with closed neutron shells, and the degree of nuclear stability in the heavy-isotope region, which terminates the r-process when such nuclei become readily unstable to spontaneous fission (currently believed to be in the neutron-rich region near A = 270 (number of nucleons) in the chart of nuclides). After the neutron flux decreases, these highly unstable radioactive nuclei quickly decay to form stable, neutron-rich nuclei. So, while the s-process creates an abundance of stable nuclei with closed neutron shells, the r-process creates an abundance of nuclei about 10 Atomic mass units below the s-process peaks, as the r-process nuclei decay back towards stability on a constant A line in the chart of nuclides.
# Astrophysical sites
The most widely believed candidate site for the r-process are core-collapse supernovae (spectral Type Ib, Ic and II), which provide the necessary physical conditions for the R-process. However, the abundance of r-process nuclei requires that either only a small fraction of supernovae eject r-process nuclei to the interstellar medium, or that each supernova ejects only a very small amount of r-process material. A recently proposed alternative solution is that neutron star mergers (a binary star system of two neutron stars that collide) may also play a role in the production of r-process nuclei, but this has yet to be observationally confirmed.
Template:Nuclear processes | https://www.wikidoc.org/index.php/R-process | |
5d58289cd73108043d58a44324afee8dd6859b36 | wikidoc | RAB11FIP1 | RAB11FIP1
Rab11 family-interacting protein 1 (Rab11-FIP1) also known as Rab-coupling protein is a protein that in humans is encoded by the RAB11FIP1 gene.
# Function
Proteins of the large Rab GTPase family (see for example RAB1A) have regulatory roles in the formation, targeting, and fusion of intracellular transport vesicles. RAB11FIP1 is one of many proteins that interact with and regulate Rab GTPases. RAB11FIP1 has been identified as a novel protein involved in the regulation of
adiponectin trafficking and release from the adipocyte. RAB11FIP1 expression, which is increased with increasing BMI in humans, inhibits the release of adiponectin from the adipocyte, potentially contributing to lower circulating levels of adiponectin observed in obese populations.
# Interactions
RAB11FIP1 has been shown to interact with RAB11A and RAB4A. | RAB11FIP1
Rab11 family-interacting protein 1 (Rab11-FIP1) also known as Rab-coupling protein is a protein that in humans is encoded by the RAB11FIP1 gene.[1][2][3]
# Function
Proteins of the large Rab GTPase family (see for example RAB1A) have regulatory roles in the formation, targeting, and fusion of intracellular transport vesicles. RAB11FIP1 is one of many proteins that interact with and regulate Rab GTPases.[2][3] RAB11FIP1 has been identified as a novel protein involved in the regulation of
adiponectin trafficking and release from the adipocyte.[4] RAB11FIP1 expression, which is increased with increasing BMI in humans, inhibits the release of adiponectin from the adipocyte, potentially contributing to lower circulating levels of adiponectin observed in obese populations.[4]
# Interactions
RAB11FIP1 has been shown to interact with RAB11A[1][2][5] and RAB4A.[1] | https://www.wikidoc.org/index.php/RAB11FIP1 | |
3134962dbbb4fa63e54da384d04fcc972bbbaf3a | wikidoc | RAB11FIP5 | RAB11FIP5
Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.
# Interactions
RAB11FIP5 has been shown to interact with RAB11A and RAB25.
# Vesicle trafficking
Rab11FIP5 is one of the many proteins that have been shown to interact with the Rab11 protein. Rab GTPases, such as Rab11, are enzymes that are involved in vesicular trafficking. Rab11 specifically plays a key role in endocytic trafficking and recycling through guiding early endosomes to endosome recycling complexes. Rab11FIP5, like most other Rab11FIP proteins, interacts with Rab11 by serving as an adaptor protein. This leads to downstream changes with regards to which proteins can interact. This is a result of the various Rab11FIP proteins that each have different binding partners. This process allows for the coordination and organization of endosomal transport and ultimately gives Rab11 its versatile function in the cell. It is believed that Rab11 recruits specific Rab11FIP proteins to the surface of vesicles in order to determine how the vesicle will behave.
Studies have shown that Rab11FIP5 localizes to the perinuclear endosomes where it aids in sorting vesicles into the slow recycling route. This process involves the transport of cargo proteins, like endocytosed receptors, to endosome recycling complexes and subsequently to the plasma membrane. This is in contrast to the fast constitutive recycling route which allows for the direct transport of cargo from the endosome to the plasma membrane. Rab11FIP5 aids in this sorting process by binding to kinesin II and forming a protein complex to regulate vesicular trafficking. Some of the proteins that are regulated through Rab11FIP5 mediated vesicle trafficking are microtubule proteins and the TfR receptor. This links Rab11FIP5 functionality to the cell cytoskeleton and the iron uptake of a cell, respectively.
# Other functions
Rab11FIP5 has been shown to play a role in the nervous system because it functions in neurons. Studies have suggested that Rab11FIP5 is involved in regulating the localization of the postsynaptic AMPA-type glutamate receptor. The AMPA receptor is an excitatory receptor that can be found on the plasma membranes of neurons. Studies have shown that mice with the Rab11FIP5 gene knocked out have severe long term neuronal depression. Without the presence of Rab11FIP5, it is hypothesized that the internalized AMPA receptors cannot be recycled back onto the plasma membrane because the receptors cannot be correctly trafficked to intracellular organelles responsible for recycling.
Rab11FIP5 has also been implicated as a protein involved in the creation of tissue polarity during development. Rab11FIP5 has been shown to be involved in the vesicle trafficking and degradation of proteins used to coordinate embryonic development. This is conducted in a manner that helps maintain the ectoderm polarity in embryonic Drosophila.
Rab11FIP5 is also suggested to be involved in aiding salivary epithelial cells to adjust to extracellular pH. V-ATPase, a proton pump protein, has been shown to be reliant on Rab11FIP5 mediated vesicle trafficking. When Rab11FIP5 is knocked down, salivary cells cannot correctly translocate V-ATPase to the plasma membrane in response to extracellular acidosis. While this pathway remains largely unknown, these results suggest a link between Rab11FIP5 function and the maintenance of the buffering capacity of saliva.
Rab11FIP5 is also required for regulated exocytosis in neuroendocrine cells. Knockdown of Rab11FIP5 inhibited calcium-stimulated dense core vesicle (DCV) exocytosis in a neuroendocrine cell line BON cells. DCV membrane proteins are lost to the plasma membrane during exocytosis and recycle to the Golgi through the retrograde trafficking pathway. The requirement of Rab11FIP5 for regulated DCV exocytosis may be attributed to its role in endosome-mediated retrograde trafficking. | RAB11FIP5
Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.[1][2][3]
# Interactions
RAB11FIP5 has been shown to interact with RAB11A[2][4][5] and RAB25.[4][5]
# Vesicle trafficking
Rab11FIP5 is one of the many proteins that have been shown to interact with the Rab11 protein.[4] Rab GTPases, such as Rab11, are enzymes that are involved in vesicular trafficking. Rab11 specifically plays a key role in endocytic trafficking and recycling through guiding early endosomes to endosome recycling complexes.[6] Rab11FIP5, like most other Rab11FIP proteins, interacts with Rab11 by serving as an adaptor protein. This leads to downstream changes with regards to which proteins can interact. This is a result of the various Rab11FIP proteins that each have different binding partners. This process allows for the coordination and organization of endosomal transport and ultimately gives Rab11 its versatile function in the cell.[6] It is believed that Rab11 recruits specific Rab11FIP proteins to the surface of vesicles in order to determine how the vesicle will behave.[7]
Studies have shown that Rab11FIP5 localizes to the perinuclear endosomes where it aids in sorting vesicles into the slow recycling route.[7] This process involves the transport of cargo proteins, like endocytosed receptors, to endosome recycling complexes and subsequently to the plasma membrane. This is in contrast to the fast constitutive recycling route which allows for the direct transport of cargo from the endosome to the plasma membrane.[7] Rab11FIP5 aids in this sorting process by binding to kinesin II and forming a protein complex to regulate vesicular trafficking. Some of the proteins that are regulated through Rab11FIP5 mediated vesicle trafficking are microtubule proteins and the TfR receptor. This links Rab11FIP5 functionality to the cell cytoskeleton and the iron uptake of a cell, respectively.[7]
# Other functions
Rab11FIP5 has been shown to play a role in the nervous system because it functions in neurons. Studies have suggested that Rab11FIP5 is involved in regulating the localization of the postsynaptic AMPA-type glutamate receptor. The AMPA receptor is an excitatory receptor that can be found on the plasma membranes of neurons. Studies have shown that mice with the Rab11FIP5 gene knocked out have severe long term neuronal depression. Without the presence of Rab11FIP5, it is hypothesized that the internalized AMPA receptors cannot be recycled back onto the plasma membrane because the receptors cannot be correctly trafficked to intracellular organelles responsible for recycling.[8]
Rab11FIP5 has also been implicated as a protein involved in the creation of tissue polarity during development. Rab11FIP5 has been shown to be involved in the vesicle trafficking and degradation of proteins used to coordinate embryonic development. This is conducted in a manner that helps maintain the ectoderm polarity in embryonic Drosophila.[9]
Rab11FIP5 is also suggested to be involved in aiding salivary epithelial cells to adjust to extracellular pH. V-ATPase, a proton pump protein, has been shown to be reliant on Rab11FIP5 mediated vesicle trafficking. When Rab11FIP5 is knocked down, salivary cells cannot correctly translocate V-ATPase to the plasma membrane in response to extracellular acidosis. While this pathway remains largely unknown, these results suggest a link between Rab11FIP5 function and the maintenance of the buffering capacity of saliva.[10]
Rab11FIP5 is also required for regulated exocytosis in neuroendocrine cells. Knockdown of Rab11FIP5 inhibited calcium-stimulated dense core vesicle (DCV) exocytosis in a neuroendocrine cell line BON cells. DCV membrane proteins are lost to the plasma membrane during exocytosis and recycle to the Golgi through the retrograde trafficking pathway. The requirement of Rab11FIP5 for regulated DCV exocytosis may be attributed to its role in endosome-mediated retrograde trafficking.[11] | https://www.wikidoc.org/index.php/RAB11FIP5 | |
b8e79b358e6ebbcd4a8eab1177a77ae8db08cfba | wikidoc | RAST test | RAST test
# Overview
A RAST test (short for radioallergosorbent test) is a blood test used to determine what a person is allergic to. This is different from a skin allergy test, which determines allergy by the reaction of a person's skin to different substances. For assessing the presence of specific IgE antibodies, allergy skin testing, when possible, is the preferred method in comparison with various in vitro tests because it is more sensitive and specific, simpler to use, and less expensive (=).
A RAST test, using a person's extracted blood, detects the amount of IgE that reacts specifically with suspected or known allergens. IgE is the antibody associated with the allergic response: if a person exhibits a high level of IgE directed against pollen, the test may indicate the person is allergic to pollen (or pollen-like) proteins. It is worth noting that a person who has outgrown an allergy may still have a positive IgE years after exposure. Because there are other tests that help with confirmation, results are best interpreted by a doctor.
The RAST was introduced in the 1970's and replaced by a superior test in 1989. Advantages of the new test range from: improved sensitivity without loss of specificity, to excellent reproducibility across the full measuring range of the calibration curve. In general, this method of blood testing (in-vitro, out of body) vs skin-prick testing (in-vivo, in body) has a major advantage: it is not always necessary to remove the patient from an anthihistamine medication regimen, and if the skin conditions (such as eczema) are so widespread that allergy skin testing can not be done, RAST tests don't affect results, it's more invasive (one venipuncture needle versus many skin pricks with a plastic device).
# History
The market-leading RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronymn RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which literature may also describe as: CAP RAST, CAP FEIA (fluorenzymeimmunoassay), and Pharmacia CAP. A review of applicable quality assessment programs shows that this new test has replaced the original RAST in approximately 80% of the world's commercial clinical laboratories, where specific IgE testing is performed. The newest version, the ImmunoCAP® Specific IgE 0-100, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/l. This clearance is based on the CLSI/NCCLS-17A Limits of Detection and Limits of Quantitation, October 2004 guideline.
RAST often are used to test for allergies when:
- a physician advises against the discontinuation of medications that can interfere with test results or cause medical complications;
- a patient suffers from severe skin conditions such as widespread eczema or psoriasis; or
- a patient has such a high sensitivity level to suspected allergens that any administration of those allergens might result in potentially serious side effects. | RAST test
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A RAST test (short for radioallergosorbent test) is a blood test used to determine what a person is allergic to. This is different from a skin allergy test, which determines allergy by the reaction of a person's skin to different substances. For assessing the presence of specific IgE antibodies, allergy skin testing, when possible, is the preferred method in comparison with various in vitro tests because it is more sensitive and specific, simpler to use, and less expensive (http://www.mayoclinicproceedings.com/inside.asp?AID=3978&UID=).
[1]
A RAST test, using a person's extracted blood, detects the amount of IgE that reacts specifically with suspected or known allergens. IgE is the antibody associated with the allergic response: if a person exhibits a high level of IgE directed against pollen, the test may indicate the person is allergic to pollen (or pollen-like) proteins. It is worth noting that a person who has outgrown an allergy may still have a positive IgE years after exposure. Because there are other tests that help with confirmation, results are best interpreted by a doctor.
The RAST was introduced in the 1970's and replaced by a superior test in 1989. Advantages of the new test range from: improved sensitivity without loss of specificity, to excellent reproducibility across the full measuring range of the calibration curve. In general, this method of blood testing (in-vitro, out of body) vs skin-prick testing (in-vivo, in body) has a major advantage: it is not always necessary to remove the patient from an anthihistamine medication regimen, and if the skin conditions (such as eczema) are so widespread that allergy skin testing can not be done, RAST tests don't affect results, it's more invasive (one venipuncture needle versus many skin pricks with a plastic device).
# History
The market-leading RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronymn RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which literature may also describe as: CAP RAST, CAP FEIA (fluorenzymeimmunoassay), and Pharmacia CAP. A review of applicable quality assessment programs shows that this new test has replaced the original RAST in approximately 80% of the world's commercial clinical laboratories, where specific IgE testing is performed. The newest version, the ImmunoCAP® Specific IgE 0-100, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/l. This clearance is based on the CLSI/NCCLS-17A Limits of Detection and Limits of Quantitation, October 2004 guideline.
RAST often are used to test for allergies when:
• a physician advises against the discontinuation of medications that can interfere with test results or cause medical complications;
• a patient suffers from severe skin conditions such as widespread eczema or psoriasis; or
• a patient has such a high sensitivity level to suspected allergens that any administration of those allergens might result in potentially serious side effects. | https://www.wikidoc.org/index.php/RAST_blood_test | |
0aff01a6f853e40cba73bfadffb077b629527003 | wikidoc | Reteplase | Reteplase
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Reteplase is a tissue plasminogen activator that is FDA approved for the {{{indicationType}}} of acute myocardial infarction. Common adverse reactions include bleeding.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Reteplase is indicated for use in the management of acute myocardial infarction (AMI) in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure and the reduction of mortality associated with AMI.
- Treatment should be initiated as soon as possible after the onset of AMI symptoms
- Dosing Information
- First dose: 10 unit IV bolus over 2 minutes
- Second dose (30 minutes after first bolus): 10 unit IV bolus over 2 minutes
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in adult patients.
### Non–Guideline-Supported Use
- Dosing Information
- 1 Unit in 2 mL and 3000 Units of heparin sodium
- Dosing Information
- First dose: 10 unit IV bolus over 2 minutes
- Second dose (30 minutes after first bolus): 10 unit IV bolus over 2 minutes
- Dosing Information
- 0.5-1.0 Units/hour (for approximately 20 hours)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Reteplase FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Reteplase in pediatric patients.
# Contraindications
- Active internal bleeding
- History of cerebrovascular accident
- Recent intracranial or intraspinal surgery or trauma
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Known bleeding diathesis
- Severe uncontrolled hypertension
# Warnings
### Bleeding
- The most common complication encountered during reteplase therapy is bleeding. The sites of bleeding include both internal bleeding sites (intracranial, retroperitoneal, gastrointestinal, genitourinary, or respiratory) and superficial bleeding sites (venous cutdowns, arterial punctures, sites of recent surgical intervention).
- The concomitant use of heparin anticoagulation may contribute to bleeding.
- In clinical trials some of the hemorrhage episodes occurred one or more days after the effects of reteplase had dissipated, but while heparin therapy was continuing.
- As fibrin is lysed during reteplase therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites, and needle puncture sites).
- Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from noncompressible sites.
- Should an arterial puncture be necessary during the administration of reteplase, it is preferable to use an upper extremity vessel that is accessible to manual compression.
- Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
- Intramuscular injections and nonessential handling of the patient should be avoided during treatment with reteplase.
- Venipunctures should be performed carefully and only as required.
- Should serious bleeding (not controllable by local pressure) occur, concomitant anticoagulant therapy should be terminated immediately.
- In addition, the second bolus of reteplase should not be given if serious bleeding occurs before it is administered.
- Each patient being considered for therapy with reteplase should be carefully evaluated and anticipated benefits weighed against the potential risks associated with therapy.
- In the following conditions, the risks of reteplase therapy may be increased and should be weighed against the anticipated benefits:
- Recent major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy
- Previous puncture of noncompressible vessels
- Cerebrovascular disease
- Recent gastrointestinal or genitourinary bleeding
- Recent trauma
- Hypertension: systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg
- High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
- Acute pericarditis
- Subacute bacterial endocarditis
- Hemostatic defects including those secondary to severe hepatic or renal disease
- Severe hepatic or renal dysfunction
- Pregnancy
- Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions
- Septic thrombophlebitis or occluded AV cannula at a seriously infected site
- Advanced age
- Patients currently receiving oral anticoagulants, e.g., warfarin sodium
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location
### Cholesterol Embolization
- Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown.
- This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
- Clinical features of cholesterol embolism may include livedo reticularis, "purple toe syndrome” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis,myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.
### Arrhythmias
- Coronary thrombolysis may result in arrhythmias associated with reperfusion.
- These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) are not different from those often seen in the ordinary course of acute myocardial infarction and should be managed with standard antiarrhythmic measures.
- It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available when reteplase is administered.
# Adverse Reactions
## Clinical Trials Experience
### Bleeding
- The most frequent adverse reaction associated with reteplase is bleeding.
- The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.
### Intracranial hemorrhage
- In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with reteplase was 0.8% (23 of 2,965 patients).
- As seen with reteplase and other thrombolytic agents, the risk for intracranial hemorrhage is increased in patients with advanced age or with elevated blood pressure.
### Other types of hemorrhage
- The incidence of other types of bleeding events in clinical studies of reteplase varied depending upon the use of arterial catheterization or other invasive procedures and whether the study was performed in Europe or the USA.
- The overall incidence of any bleeding event in patients treated with reteplase in clinical studies (n = 3,805) was 21.1%.
- The rates for bleeding events, regardless of severity, for the 10 + 10 unit reteplase regimen from controlled clinical studies are summarized in Table 3.
- In these studies the severity and sites of bleeding events were comparable for reteplase and the comparison thrombolytic agents.
- Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, any concomitant heparin should be terminated immediately.
- In addition, the second bolus of reteplase should not be given if the serious bleeding occurs before it is administered.
- Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.
- Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during reteplase therapy.
- Therefore, reteplasetherapy requires careful attention to potential bleeding sites (e.g., catheter insertion sites, arterial puncture sites).
### Allergic Reactions
- Among the 2,965 patients receiving reteplase in the INJECT trial, serious allergic reactions were noted in 3 patients, with one patient experiencing dyspnea and hypotension.
- No anaphylactoid reactions were observed among the 3,856 patients treated with reteplase in initial clinical trials.
- In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving reteplase.
### Other Adverse Reactions
- Patients administered reteplase as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to reteplase therapy.
- These events includecardiogenic shock, arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation), AV block, pulmonary edema,heart failure, cardiac arrest, recurrent ischemia, reinfarction, myocardial rupture, mitral regurgitation, pericardial effusion, pericarditis, cardiac tamponade, venous thrombosisand embolism, and electromechanical dissociation.
- These events can be life-threatening and may lead to death.
- Other adverse events have been reported, including nausea and/or vomiting, hypotension, and fever.
## Postmarketing Experience
There is limited information regarding Reteplase Postmarketing Experience in the drug label.
# Drug Interactions
- The interaction of reteplase with other cardioactive drugs has not been studied.
- In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as aspirin, dipyridamole, and abciximab) may increase the risk of bleeding if administered prior to or after reteplase therapy.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
Reteplase has been shown to have an abortifacient effect in rabbits when given in doses 3 times the human dose (0.86 units/kg). Reproduction studies performed in rats at doses up to 15 times the human dose (4.31 units/kg) revealed no evidence of fetal anomalies; however, Reteplase administered to pregnant rabbits resulted in hemorrhaging in the genital tract, leading to abortions in mid-gestation. There are no adequate and well-controlled studies in pregnant women. The most common complication of thrombolytic therapy is bleeding and certain conditions, including pregnancy, can increase this risk. Reteplase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS): C
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
### Labor and Delivery
There is no FDA guidance on use of Reteplase during labor and delivery.
### Nursing Mothers
It is not known whether reteplase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Retavase® is administered to a nursing woman.
### Pediatric Use
Safety and effectiveness of reteplase in pediatric patients have not been established.
### Geriatic Use
There is no FDA guidance on the use of Reteplase in geriatric settings.
### Gender
There is no FDA guidance on the use of Reteplase with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Reteplase with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Reteplase in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Reteplase in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Reteplase in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Reteplase in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Reteplase is for intravenous administration only. Reteplase is administered as a 10 + 10 unit double-bolus injection. Two 10 unit bolus injections are required for a complete treatment. Each bolus is administered as an intravenous injection over 2 minutes. The second bolus is given 30 minutes after initiation of the first bolus injection. Each bolus injection should be given via an intravenous line in which no other medication is being simultaneously injected or infused. No other medication should be added to the injection solution containing reteplase. There is no experience with patients receiving repeat courses of therapy with reteplase.
Heparin and reteplase are incompatible when combined in solution.
'Do not administer heparin and reteplase simultaneously in the same intravenous line.'
If reteplase is to be injected through an intravenous line containing heparin, a normal saline or 5% dextrose (D5W) solution should be flushed through the line prior to and following the reteplase injection.
Although the value of anticoagulants and antiplatelet drugs during and following administration of reteplase has not been studied, heparin has been administered concomitantly in more than 99% of patients. Aspirin has been given either during and/or following heparin treatment. Studies assessing the safety and efficacy of reteplase without adjunctive therapy with heparin and aspirin have not been performed.
Reconstitution – Reteplase Kit and Reteplase Half-Kit: Reconstitution should be carried out using the diluent and dispensing pin provided with reteplase. It is important that reteplase be reconstituted only with the supplied Sterile Water for Injection, USP (without preservatives). The reconstituted preparation results in a colorless solution containing reteplase 1 unit/mL. Slight foaming upon reconstitution is not unusual; allowing the vial to stand undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles.
Because reteplase contains no antibacterial preservatives, it should be reconstituted immediately before use. When reconstituted as directed, the solution may be used within 4 hours when stored at 2-30°C (36-86°F). Prior to administration, the product should be visually inspected for particulate matter and discoloration.
Use aseptic technique throughout.
- Step 1: Withdraw 10 mL of Sterile Water for Injection, USP (SWFI) from the supplied vial into a sterile 10 mL syringe.
- Step 2: Open the package containing the dispensing pin. Remove the protective cap from the luer lock port of the dispensing pin and connect the sterile 10mL syringe to the dispensing pin. Remove the protective flip-cap from one vial of reteplase.
- Step 3: Remove the protective cap from the spike end of the dispensing pin, and insert the spike into the vial of reteplase until the security clips lock onto the vial.
Transfer the 10 mL of SWFI through the dispensing pin into the vial of reteplase.
- Step 4: With the dispensing pin and syringe still attached to the vial, swirl the vial gently to dissolve the reteplase. DO NOT SHAKE.
- Step 5: Withdraw 10 mL of reteplase reconstituted solution back into the syringe. A small amount of solution will remain in the vial due to overfill.
- Step 6: Detach the syringe from the dispensing pin, and attach a sterile needle.
- Step 7: The 10 mL bolus dose is now ready for administration. Safely discard all used reconstitution components and the empty reteplase vial according to institutional procedures.
### Monitoring
- Administration of reteplase may cause decreases in plasminogen and fibrinogen. During reteplase therapy, if coagulation tests and/or measurements of fibrinolytic activity are performed, the results may be unreliable unless specific precautions are taken to prevent in vitro artifacts.
- Reteplase is an enzyme that when present in blood in pharmacologic concentrations remains active under in vitro conditions.
- This can lead to degradation of fibrinogen in blood samples removed for analysis.
- Collection of blood samples in the presence of PPACK (chloromethylketone) at 2 µM concentrations was used in clinical trials to prevent in vitro fibrinolytic artifacts.
- Heparin and aspirin have been administered concomitantly with and following the administration of reteplase in the management of acute myocardial infarction.
- Because heparin, aspirin, or reteplase may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.
# IV Compatibility
- Heparin and reteplase are incompatible when combined in solution
- Do not administer heparin and reteplase simultaneously in the same intravenous line.
# Overdosage
There is limited information regarding Reteplase overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
Reteplase is a recombinant plasminogen activator which catalyzes the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.1,2In a controlled trial, 36 of 56 patients treated for an acute myocardial infarction (AMI) had a decrease in fibrinogen levels to below 100 mg/dL by 2 hours following the administration of reteplase as a double-bolus intravenous injection (10 + 10 unit) in which 10 units (17.4 mg) was followed 30 minutes later by a second bolus of 10 units (17.4 mg).3 The mean fibrinogen level returned to the baseline value by 48 hours.
## Structure
Reteplase is a non-glycosylated deletion mutein of tissue plasminogen activator (tPA), containing the kringle 2 and the protease domains of human tPA. Reteplase contains 355 of the 527 amino acids of native tPA (amino acids 1-3 and 176-527). Reteplase is produced by recombinant DNA technology in E. coli. The protein is isolated as inactive inclusion bodies from E. coli, converted into its active form by an in vitro folding process and purified by chromatographic separation. The molecular weight of Reteplase is 39,571 daltons.
## Pharmacodynamics
There is limited information regarding Reteplase Pharmacodynamics in the drug label.
## Pharmacokinetics
Based on the measurement of thrombolytic activity, reteplase is cleared from plasma at a rate of 250-450 mL/min, with an effective half-life of 13-16 minutes. Reteplase is cleared primarily by the liver and kidney.
## Nonclinical Toxicology
### Carcinogenesis, Mutagenesis, Impairment of Fertility
- Long-term studies in animals have not been performed to evaluate the carcinogenic potential of reteplase.
- Studies to determine mutagenicity, chromosomal aberrations, gene mutations, and micronuclei induction were negative at all concentrations tested.
- Reproductive toxicity studies in rats revealed no effects on fertility at doses up to 15 times the human dose (4.31 units/kg).
# Clinical Studies
The safety and efficacy of reteplase were evaluated in three controlled clinical trials in which reteplase was compared to other thrombolytic agents. The INJECT study was designed to assess the relative effects of reteplase or the Streptase® brand of streptokinase upon mortality rates at 35 days following an AMI. The other studies (RAPID 1 and RAPID 2) were arteriographic studies which compared the effect on coronary patency of reteplase to two regimens of alteplase (a tissue plasminogen activator; Activase® in the USA and Actilyse® in Europe) in patients with an AMI. In all three studies, patients were treated with aspirin (initial doses of 160 mg to 350 mg and subsequent doses of 75 mg to 350 mg) and heparin (a 5,000 unit IV bolus prior to the administration of reteplase, followed by a 1000 unit/hour continuous IV infusion for at least 24 hours).3,4,5 The safety and efficacy of reteplase have not been evaluated using antithrombotic or antiplatelet regimens other than those described above.
Reteplase (10 + 10 unit) was compared to streptokinase (1.5 million units over 60 minutes) in a double-blind, randomized, European study (INJECT), which studied 6,010 patients treated within 12 hours of the onset of symptoms of AMI. To be eligible for enrollment, patients had to have chest pain consistent with coronary ischemia and ST segment elevation, or a bundle branch block pattern on the EKG. Patients with known cerebrovascular or other bleeding risks or those with a systolic blood pressure >200 mm Hg or a diastolic blood pressure >100 mm Hg were excluded from enrollment. The results of the primary endpoint (mortality at 35 days), six month mortality and selected other 35 day endpoints are shown in Table 1 for patients receiving study medications.
For mortality, stroke and the combined outcome of mortality or stroke, the 95% confidence intervals in Table 1 reflect the range within which the true difference in outcomes probably lies and includes the possibility of no difference. The incidences of congestive heart failure and of cardiogenic shock were significantly lower among patients treated with reteplase.
The total incidence of stroke was similar between the groups. However, more patients treated with reteplase experienced hemorrhagic strokes than patients treated with streptokinase. An exploratory analysis indicated that the incidence of intracranial hemorrhage was higher among older patients or those with elevated blood pressure. The incidence of intracranial hemorrhage among the 698 patients treated with reteplase who were older than 70 years was 2.2%. Intracranial hemorrhage occurred in 8 of the 332 (2.4%) patients treated with reteplase who had an initial systolic blood pressure >160 mm Hg and in 15 of the 2,629 (0.6%) reteplase patients who had an initial systolic blood pressure <160 mm Hg.
Two arteriographic studies (RAPID 1 and RAPID 2) were performed utilizing open-label administration of the study agents and a blinded review of the arteriograms. In RAPID 1, patients were treated within 6 hours of the onset of symptoms, and in RAPID 2, patients were treated within 12 hours of the onset of symptoms. Both studies evaluated coronary artery perfusion through the infarct-related artery 90 minutes after the initiation of therapy as the primary endpoint. Some patients in each study also had perfusion through the infarct-related artery evaluated at 60 minutes after the initiation of therapy. In RAPID 1, reteplase (in doses of 10 + 10 unit, 15 unit, or 10 + 5 unit) was compared to a 3 hour regimen of alteplase (100 mg administered over 3 hrs).In RAPID 2, reteplase (10 + 10 unit) was compared to an accelerated regimen of alteplase (100 mg administered over 1.5 hrs). The percentages of patients with partial or complete flow (TIMI grades 2 or 3) and complete flow (TIMI grade 3), are shown along with ventricular function assessments in Table 2. The follow-up arteriogram was performed at a median of 8 (RAPID 1) and 5 (RAPID 2) days following the administration of the thrombolytics. In RAPID 1 the best patency results were obtained with the 10 + 10 unit dose. In RAPID 2, the percentage of patients with partial or complete flow and the percentage of patients with complete flow was significantly higher with reteplase than with alteplaseat 90 minutes after the initiation of therapy. In both clinical trials the reocclusion rates were similar for reteplase and alteplase. The relationship between coronary artery patency and clinical efficacy has not been established.
Approximately 70% (RAPID 1) and 78% (RAPID 2) of the patients in the arteriographic studies underwent optional arteriography at 60 minutes following the administration of the study agents. In both trials the percentage of patients with complete flow at 60 minutes was significantly higher with reteplase than with alteplase. Neither RAPID clinical trial was designed nor powered to compare the efficacy or safety of reteplase and alteplase with respect to the outcomes of mortality and stroke.
# How Supplied
Reteplase, is supplied as a sterile, preservative-free, lyophilized powder in 10.4 unit (equivalent to 18.1 mg reteplase) vials without a vacuum, in the following packaging configurations:
Reteplase Kit: 2 single-use reteplase vials 10.4 units (18.1 mg), 2 single-use diluent vials for reconstitution (10 mL Sterile Water for Injection, USP), 2 sterile 10 mL syringes, 2 sterile dispensing pins, 4 sterile needles, 2 alcohol swabs and a package insert;
Reteplase Half-Kit: 1 single-use reteplase vial 10.4 units (18.1 mg), 1 single-use diluent vial for reconstitution (10 mL Sterile Water for Injection, USP), a sterile dispensing pin and a package insert.
## Storage
Store reteplase at 2-25°C (36-77°F). The box should remain sealed until use to protect the lyophilisate from exposure to light. Do not use beyond the expiration date printed on the box.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Reteplase in the drug label.
# Precautions with Alcohol
Alcohol-Reteplase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Retavase
# Look-Alike Drug Names
There is limited information regarding Reteplase Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | Reteplase
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
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# Overview
Reteplase is a tissue plasminogen activator that is FDA approved for the {{{indicationType}}} of acute myocardial infarction. Common adverse reactions include bleeding.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Reteplase is indicated for use in the management of acute myocardial infarction (AMI) in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure and the reduction of mortality associated with AMI.
- Treatment should be initiated as soon as possible after the onset of AMI symptoms
- Dosing Information
- First dose: 10 unit IV bolus over 2 minutes
- Second dose (30 minutes after first bolus): 10 unit IV bolus over 2 minutes
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in adult patients.
### Non–Guideline-Supported Use
- Dosing Information
- 1 Unit in 2 mL and 3000 Units of heparin sodium [1]
- Dosing Information
- First dose: 10 unit IV bolus over 2 minutes
- Second dose (30 minutes after first bolus): 10 unit IV bolus over 2 minutes[2]
- Dosing Information
- 0.5-1.0 Units/hour (for approximately 20 hours)[3]
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Reteplase FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Reteplase in pediatric patients.
# Contraindications
- Active internal bleeding
- History of cerebrovascular accident
- Recent intracranial or intraspinal surgery or trauma
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Known bleeding diathesis
- Severe uncontrolled hypertension
# Warnings
### Bleeding
- The most common complication encountered during reteplase therapy is bleeding. The sites of bleeding include both internal bleeding sites (intracranial, retroperitoneal, gastrointestinal, genitourinary, or respiratory) and superficial bleeding sites (venous cutdowns, arterial punctures, sites of recent surgical intervention).
- The concomitant use of heparin anticoagulation may contribute to bleeding.
- In clinical trials some of the hemorrhage episodes occurred one or more days after the effects of reteplase had dissipated, but while heparin therapy was continuing.
- As fibrin is lysed during reteplase therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites, and needle puncture sites).
- Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from noncompressible sites.
- Should an arterial puncture be necessary during the administration of reteplase, it is preferable to use an upper extremity vessel that is accessible to manual compression.
- Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
- Intramuscular injections and nonessential handling of the patient should be avoided during treatment with reteplase.
- Venipunctures should be performed carefully and only as required.
- Should serious bleeding (not controllable by local pressure) occur, concomitant anticoagulant therapy should be terminated immediately.
- In addition, the second bolus of reteplase should not be given if serious bleeding occurs before it is administered.
- Each patient being considered for therapy with reteplase should be carefully evaluated and anticipated benefits weighed against the potential risks associated with therapy.
- In the following conditions, the risks of reteplase therapy may be increased and should be weighed against the anticipated benefits:
- Recent major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy
- Previous puncture of noncompressible vessels
- Cerebrovascular disease
- Recent gastrointestinal or genitourinary bleeding
- Recent trauma
- Hypertension: systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg
- High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
- Acute pericarditis
- Subacute bacterial endocarditis
- Hemostatic defects including those secondary to severe hepatic or renal disease
- Severe hepatic or renal dysfunction
- Pregnancy
- Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions
- Septic thrombophlebitis or occluded AV cannula at a seriously infected site
- Advanced age
- Patients currently receiving oral anticoagulants, e.g., warfarin sodium
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location
### Cholesterol Embolization
- Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown.
- This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
- Clinical features of cholesterol embolism may include livedo reticularis, "purple toe syndrome” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis,myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.
### Arrhythmias
- Coronary thrombolysis may result in arrhythmias associated with reperfusion.
- These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) are not different from those often seen in the ordinary course of acute myocardial infarction and should be managed with standard antiarrhythmic measures.
- It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available when reteplase is administered.
# Adverse Reactions
## Clinical Trials Experience
### Bleeding
- The most frequent adverse reaction associated with reteplase is bleeding.
- The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.
### Intracranial hemorrhage
- In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with reteplase was 0.8% (23 of 2,965 patients).
- As seen with reteplase and other thrombolytic agents, the risk for intracranial hemorrhage is increased in patients with advanced age or with elevated blood pressure.
### Other types of hemorrhage
- The incidence of other types of bleeding events in clinical studies of reteplase varied depending upon the use of arterial catheterization or other invasive procedures and whether the study was performed in Europe or the USA.
- The overall incidence of any bleeding event in patients treated with reteplase in clinical studies (n = 3,805) was 21.1%.
- The rates for bleeding events, regardless of severity, for the 10 + 10 unit reteplase regimen from controlled clinical studies are summarized in Table 3.
- In these studies the severity and sites of bleeding events were comparable for reteplase and the comparison thrombolytic agents.
- Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, any concomitant heparin should be terminated immediately.
- In addition, the second bolus of reteplase should not be given if the serious bleeding occurs before it is administered.
- Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.
- Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during reteplase therapy.
- Therefore, reteplasetherapy requires careful attention to potential bleeding sites (e.g., catheter insertion sites, arterial puncture sites).
### Allergic Reactions
- Among the 2,965 patients receiving reteplase in the INJECT trial, serious allergic reactions were noted in 3 patients, with one patient experiencing dyspnea and hypotension.
- No anaphylactoid reactions were observed among the 3,856 patients treated with reteplase in initial clinical trials.
- In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving reteplase.
### Other Adverse Reactions
- Patients administered reteplase as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to reteplase therapy.
- These events includecardiogenic shock, arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation), AV block, pulmonary edema,heart failure, cardiac arrest, recurrent ischemia, reinfarction, myocardial rupture, mitral regurgitation, pericardial effusion, pericarditis, cardiac tamponade, venous thrombosisand embolism, and electromechanical dissociation.
- These events can be life-threatening and may lead to death.
- Other adverse events have been reported, including nausea and/or vomiting, hypotension, and fever.
## Postmarketing Experience
There is limited information regarding Reteplase Postmarketing Experience in the drug label.
# Drug Interactions
- The interaction of reteplase with other cardioactive drugs has not been studied.
- In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as aspirin, dipyridamole, and abciximab) may increase the risk of bleeding if administered prior to or after reteplase therapy.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
Reteplase has been shown to have an abortifacient effect in rabbits when given in doses 3 times the human dose (0.86 units/kg). Reproduction studies performed in rats at doses up to 15 times the human dose (4.31 units/kg) revealed no evidence of fetal anomalies; however, Reteplase administered to pregnant rabbits resulted in hemorrhaging in the genital tract, leading to abortions in mid-gestation. There are no adequate and well-controlled studies in pregnant women. The most common complication of thrombolytic therapy is bleeding and certain conditions, including pregnancy, can increase this risk. Reteplase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS): C
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
### Labor and Delivery
There is no FDA guidance on use of Reteplase during labor and delivery.
### Nursing Mothers
It is not known whether reteplase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Retavase® is administered to a nursing woman.
### Pediatric Use
Safety and effectiveness of reteplase in pediatric patients have not been established.
### Geriatic Use
There is no FDA guidance on the use of Reteplase in geriatric settings.
### Gender
There is no FDA guidance on the use of Reteplase with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Reteplase with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Reteplase in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Reteplase in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Reteplase in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Reteplase in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Reteplase is for intravenous administration only. Reteplase is administered as a 10 + 10 unit double-bolus injection. Two 10 unit bolus injections are required for a complete treatment. Each bolus is administered as an intravenous injection over 2 minutes. The second bolus is given 30 minutes after initiation of the first bolus injection. Each bolus injection should be given via an intravenous line in which no other medication is being simultaneously injected or infused. No other medication should be added to the injection solution containing reteplase. There is no experience with patients receiving repeat courses of therapy with reteplase.
Heparin and reteplase are incompatible when combined in solution.
'Do not administer heparin and reteplase simultaneously in the same intravenous line.'
If reteplase is to be injected through an intravenous line containing heparin, a normal saline or 5% dextrose (D5W) solution should be flushed through the line prior to and following the reteplase injection.
Although the value of anticoagulants and antiplatelet drugs during and following administration of reteplase has not been studied, heparin has been administered concomitantly in more than 99% of patients. Aspirin has been given either during and/or following heparin treatment. Studies assessing the safety and efficacy of reteplase without adjunctive therapy with heparin and aspirin have not been performed.
Reconstitution – Reteplase Kit and Reteplase Half-Kit: Reconstitution should be carried out using the diluent and dispensing pin provided with reteplase. It is important that reteplase be reconstituted only with the supplied Sterile Water for Injection, USP (without preservatives). The reconstituted preparation results in a colorless solution containing reteplase 1 unit/mL. Slight foaming upon reconstitution is not unusual; allowing the vial to stand undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles.
Because reteplase contains no antibacterial preservatives, it should be reconstituted immediately before use. When reconstituted as directed, the solution may be used within 4 hours when stored at 2-30°C (36-86°F). Prior to administration, the product should be visually inspected for particulate matter and discoloration.
Use aseptic technique throughout.
- Step 1: Withdraw 10 mL of Sterile Water for Injection, USP (SWFI) from the supplied vial into a sterile 10 mL syringe.
- Step 2: Open the package containing the dispensing pin. Remove the protective cap from the luer lock port of the dispensing pin and connect the sterile 10mL syringe to the dispensing pin. Remove the protective flip-cap from one vial of reteplase.
- Step 3: Remove the protective cap from the spike end of the dispensing pin, and insert the spike into the vial of reteplase until the security clips lock onto the vial.
Transfer the 10 mL of SWFI through the dispensing pin into the vial of reteplase.
- Step 4: With the dispensing pin and syringe still attached to the vial, swirl the vial gently to dissolve the reteplase. DO NOT SHAKE.
- Step 5: Withdraw 10 mL of reteplase reconstituted solution back into the syringe. A small amount of solution will remain in the vial due to overfill.
- Step 6: Detach the syringe from the dispensing pin, and attach a sterile needle.
- Step 7: The 10 mL bolus dose is now ready for administration. Safely discard all used reconstitution components and the empty reteplase vial according to institutional procedures.
### Monitoring
- Administration of reteplase may cause decreases in plasminogen and fibrinogen. During reteplase therapy, if coagulation tests and/or measurements of fibrinolytic activity are performed, the results may be unreliable unless specific precautions are taken to prevent in vitro artifacts.
- Reteplase is an enzyme that when present in blood in pharmacologic concentrations remains active under in vitro conditions.
- This can lead to degradation of fibrinogen in blood samples removed for analysis.
- Collection of blood samples in the presence of PPACK (chloromethylketone) at 2 µM concentrations was used in clinical trials to prevent in vitro fibrinolytic artifacts.
- Heparin and aspirin have been administered concomitantly with and following the administration of reteplase in the management of acute myocardial infarction.
- Because heparin, aspirin, or reteplase may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.
# IV Compatibility
- Heparin and reteplase are incompatible when combined in solution
- Do not administer heparin and reteplase simultaneously in the same intravenous line.
# Overdosage
There is limited information regarding Reteplase overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
Reteplase is a recombinant plasminogen activator which catalyzes the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.1,2In a controlled trial, 36 of 56 patients treated for an acute myocardial infarction (AMI) had a decrease in fibrinogen levels to below 100 mg/dL by 2 hours following the administration of reteplase as a double-bolus intravenous injection (10 + 10 unit) in which 10 units (17.4 mg) was followed 30 minutes later by a second bolus of 10 units (17.4 mg).3 The mean fibrinogen level returned to the baseline value by 48 hours.
## Structure
Reteplase is a non-glycosylated deletion mutein of tissue plasminogen activator (tPA), containing the kringle 2 and the protease domains of human tPA. Reteplase contains 355 of the 527 amino acids of native tPA (amino acids 1-3 and 176-527). Reteplase is produced by recombinant DNA technology in E. coli. The protein is isolated as inactive inclusion bodies from E. coli, converted into its active form by an in vitro folding process and purified by chromatographic separation. The molecular weight of Reteplase is 39,571 daltons.
## Pharmacodynamics
There is limited information regarding Reteplase Pharmacodynamics in the drug label.
## Pharmacokinetics
Based on the measurement of thrombolytic activity, reteplase is cleared from plasma at a rate of 250-450 mL/min, with an effective half-life of 13-16 minutes. Reteplase is cleared primarily by the liver and kidney.
## Nonclinical Toxicology
### Carcinogenesis, Mutagenesis, Impairment of Fertility
- Long-term studies in animals have not been performed to evaluate the carcinogenic potential of reteplase.
- Studies to determine mutagenicity, chromosomal aberrations, gene mutations, and micronuclei induction were negative at all concentrations tested.
- Reproductive toxicity studies in rats revealed no effects on fertility at doses up to 15 times the human dose (4.31 units/kg).
# Clinical Studies
The safety and efficacy of reteplase were evaluated in three controlled clinical trials in which reteplase was compared to other thrombolytic agents. The INJECT study was designed to assess the relative effects of reteplase or the Streptase® brand of streptokinase upon mortality rates at 35 days following an AMI. The other studies (RAPID 1 and RAPID 2) were arteriographic studies which compared the effect on coronary patency of reteplase to two regimens of alteplase (a tissue plasminogen activator; Activase® in the USA and Actilyse® in Europe) in patients with an AMI. In all three studies, patients were treated with aspirin (initial doses of 160 mg to 350 mg and subsequent doses of 75 mg to 350 mg) and heparin (a 5,000 unit IV bolus prior to the administration of reteplase, followed by a 1000 unit/hour continuous IV infusion for at least 24 hours).3,4,5 The safety and efficacy of reteplase have not been evaluated using antithrombotic or antiplatelet regimens other than those described above.
Reteplase (10 + 10 unit) was compared to streptokinase (1.5 million units over 60 minutes) in a double-blind, randomized, European study (INJECT), which studied 6,010 patients treated within 12 hours of the onset of symptoms of AMI. To be eligible for enrollment, patients had to have chest pain consistent with coronary ischemia and ST segment elevation, or a bundle branch block pattern on the EKG. Patients with known cerebrovascular or other bleeding risks or those with a systolic blood pressure >200 mm Hg or a diastolic blood pressure >100 mm Hg were excluded from enrollment. The results of the primary endpoint (mortality at 35 days), six month mortality and selected other 35 day endpoints are shown in Table 1 for patients receiving study medications.
For mortality, stroke and the combined outcome of mortality or stroke, the 95% confidence intervals in Table 1 reflect the range within which the true difference in outcomes probably lies and includes the possibility of no difference. The incidences of congestive heart failure and of cardiogenic shock were significantly lower among patients treated with reteplase.
The total incidence of stroke was similar between the groups. However, more patients treated with reteplase experienced hemorrhagic strokes than patients treated with streptokinase. An exploratory analysis indicated that the incidence of intracranial hemorrhage was higher among older patients or those with elevated blood pressure. The incidence of intracranial hemorrhage among the 698 patients treated with reteplase who were older than 70 years was 2.2%. Intracranial hemorrhage occurred in 8 of the 332 (2.4%) patients treated with reteplase who had an initial systolic blood pressure >160 mm Hg and in 15 of the 2,629 (0.6%) reteplase patients who had an initial systolic blood pressure <160 mm Hg.
Two arteriographic studies (RAPID 1 and RAPID 2) were performed utilizing open-label administration of the study agents and a blinded review of the arteriograms. In RAPID 1, patients were treated within 6 hours of the onset of symptoms, and in RAPID 2, patients were treated within 12 hours of the onset of symptoms. Both studies evaluated coronary artery perfusion through the infarct-related artery 90 minutes after the initiation of therapy as the primary endpoint. Some patients in each study also had perfusion through the infarct-related artery evaluated at 60 minutes after the initiation of therapy. In RAPID 1, reteplase (in doses of 10 + 10 unit, 15 unit, or 10 + 5 unit) was compared to a 3 hour regimen of alteplase (100 mg administered over 3 hrs).In RAPID 2, reteplase (10 + 10 unit) was compared to an accelerated regimen of alteplase (100 mg administered over 1.5 hrs). The percentages of patients with partial or complete flow (TIMI grades 2 or 3) and complete flow (TIMI grade 3), are shown along with ventricular function assessments in Table 2. The follow-up arteriogram was performed at a median of 8 (RAPID 1) and 5 (RAPID 2) days following the administration of the thrombolytics. In RAPID 1 the best patency results were obtained with the 10 + 10 unit dose. In RAPID 2, the percentage of patients with partial or complete flow and the percentage of patients with complete flow was significantly higher with reteplase than with alteplaseat 90 minutes after the initiation of therapy. In both clinical trials the reocclusion rates were similar for reteplase and alteplase. The relationship between coronary artery patency and clinical efficacy has not been established.
Approximately 70% (RAPID 1) and 78% (RAPID 2) of the patients in the arteriographic studies underwent optional arteriography at 60 minutes following the administration of the study agents. In both trials the percentage of patients with complete flow at 60 minutes was significantly higher with reteplase than with alteplase. Neither RAPID clinical trial was designed nor powered to compare the efficacy or safety of reteplase and alteplase with respect to the outcomes of mortality and stroke.
# How Supplied
Reteplase, is supplied as a sterile, preservative-free, lyophilized powder in 10.4 unit (equivalent to 18.1 mg reteplase) vials without a vacuum, in the following packaging configurations:
Reteplase Kit: 2 single-use reteplase vials 10.4 units (18.1 mg), 2 single-use diluent vials for reconstitution (10 mL Sterile Water for Injection, USP), 2 sterile 10 mL syringes, 2 sterile dispensing pins, 4 sterile needles, 2 alcohol swabs and a package insert;
Reteplase Half-Kit: 1 single-use reteplase vial 10.4 units (18.1 mg), 1 single-use diluent vial for reconstitution (10 mL Sterile Water for Injection, USP), a sterile dispensing pin and a package insert.
## Storage
Store reteplase at 2-25°C (36-77°F). The box should remain sealed until use to protect the lyophilisate from exposure to light. Do not use beyond the expiration date printed on the box.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Reteplase in the drug label.
# Precautions with Alcohol
Alcohol-Reteplase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
Retavase
# Look-Alike Drug Names
There is limited information regarding Reteplase Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/RPA |
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