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f7f79154119ba58c07e45cb44b982c58c2c11a27	wikidoc	Kiaa1107	Kiaa1107 KIAA1107 is a protein that in humans is encoded by the KIAA1107 gene. KIAA1107 is a Serine-rich protein, whose expression was found to increase in white matter of Multiple Sclerosis brain lesions. # Gene ## General Information KIAA1107 is a protein encoding gene, located on chromosome 1 in Homo sapiens. Its exact location is at cytogenetic band 1p22.1, with the genomic location of 92,067,052 bp - 92,184,723 bp from pter, with 17,672 total bases. The KIAA1107 gene contains nine known exons. # Protein ## General Properties Uncharacterized Protein KIAA1107 is 1401 amino acids in length in the most common variant, isoform A, found in Homo sapiens. The predicted molecular weight of isoform A in Homo sapiens is 149.6 kdal. ## Composition KIAA1107 has a higher frequency of Serine and Aspartate and a lower frequency of Tyrosine than in the average protein in Homo sapiens. Uncharacterized protein is composed of 7.5% Aspartate and 14.0% Serine, which constitutes it as a Serine-rich protein. This protein also consists of 0.7% Tyrosine, which is considered to be below average in human proteins. # mRNA ## Isoforms Transcription of KIAA1107 produces 6 different mRNAs, with 4 alternatively spliced variants and 2 unspliced forms. Variant A is the most commonly occurring and longest variant of KIAA1107 in humans. Variant A contains nine exons (1-9) present in their standard form. Variant B contains seven exons (3-9) present in standard form. Variant C-U contains one exon, which is an alternatively spliced variant of exon 8. Variant D contains five exons (1-4, 5a) with 1-4 occurring in their standard form and an alternative form of exon 5. Variant E contains three exons, which are alternatively spliced forms of exons 3, 4, and 5. Variant F-U contains one exon, which is an alternatively spliced form of exon 5a, which occurs in variant D. ## Conserved Domains There is a domain, DUF4596, present from 1311 - 1354 in KIAA1107. The function of this domain is unknown. # Expression ## Tissue Expression Expression of KIAA1107 does not appear to be ubiquitous in Homo sapiens. KIAA1107 is found to be expressed mostly in the brain, with lower levels of expression occurring in the bladder, mammary gland, muscle, prostate, and testis. Within the brain, KIAA1107 is expressed highest in the pineal gland, prefrontal cortex, cingulate cortex, and subthalamic nucleus. ## Disease Association KIAA1107 was found to be over expressed in brain white matter with Multiple Sclerosis brain lesions when compared to control white matter. The average non-diseased sample had negligible expression of KIAA1107, while in the diseased sample it was expressed higher than almost any other gene (95th-98th percentile of expression). # Homology ## Orthologs Orthologs of KIAA1107 exist in most vertebrates. The most distant homolog of KIAA1107 was found in, a fish, the Amazon Molly. There were no homologs found for sharks and rays, which would suggest that KIAA1107 originated in fish. There are no human paralogs for KIAA1107.	Kiaa1107 KIAA1107 is a protein that in humans is encoded by the KIAA1107 gene. [1] KIAA1107 is a Serine-rich protein, whose expression was found to increase in white matter of Multiple Sclerosis brain lesions. [2] [3] # Gene ## General Information KIAA1107 is a protein encoding gene, located on chromosome 1 in Homo sapiens. Its exact location is at cytogenetic band 1p22.1, with the genomic location of 92,067,052 bp - 92,184,723 bp from pter, with 17,672 total bases. [4] The KIAA1107 gene contains nine known exons. [5] # Protein ## General Properties Uncharacterized Protein KIAA1107 is 1401 amino acids in length in the most common variant, isoform A, found in Homo sapiens. [5] The predicted molecular weight of isoform A in Homo sapiens is 149.6 kdal. [2] ## Composition KIAA1107 has a higher frequency of Serine and Aspartate and a lower frequency of Tyrosine than in the average protein in Homo sapiens. Uncharacterized protein is composed of 7.5% Aspartate and 14.0% Serine, which constitutes it as a Serine-rich protein. This protein also consists of 0.7% Tyrosine, which is considered to be below average in human proteins. [2] # mRNA ## Isoforms Transcription of KIAA1107 produces 6 different mRNAs, with 4 alternatively spliced variants and 2 unspliced forms. Variant A is the most commonly occurring and longest variant of KIAA1107 in humans. [5] Variant A contains nine exons (1-9) present in their standard form. Variant B contains seven exons (3-9) present in standard form. Variant C-U contains one exon, which is an alternatively spliced variant of exon 8. Variant D contains five exons (1-4, 5a) with 1-4 occurring in their standard form and an alternative form of exon 5. Variant E contains three exons, which are alternatively spliced forms of exons 3, 4, and 5. Variant F-U contains one exon, which is an alternatively spliced form of exon 5a, which occurs in variant D. [5] ## Conserved Domains There is a domain, DUF4596, present from 1311 - 1354 in KIAA1107. The function of this domain is unknown. [6] # Expression ## Tissue Expression Expression of KIAA1107 does not appear to be ubiquitous in Homo sapiens. KIAA1107 is found to be expressed mostly in the brain, with lower levels of expression occurring in the bladder, mammary gland, muscle, prostate, and testis. [7] Within the brain, KIAA1107 is expressed highest in the pineal gland, prefrontal cortex, cingulate cortex, and subthalamic nucleus. [8] ## Disease Association KIAA1107 was found to be over expressed in brain white matter with Multiple Sclerosis brain lesions when compared to control white matter. The average non-diseased sample had negligible expression of KIAA1107, while in the diseased sample it was expressed higher than almost any other gene (95th-98th percentile of expression). [3] # Homology ## Orthologs Orthologs of KIAA1107 exist in most vertebrates. The most distant homolog of KIAA1107 was found in, a fish, the Amazon Molly. There were no homologs found for sharks and rays, which would suggest that KIAA1107 originated in fish. [9] There are no human paralogs for KIAA1107.	https://www.wikidoc.org/index.php/Kiaa1107
67cb853ef32bb0b66b5c23c650f8756d0136fa68	wikidoc	Kingella	Kingella Kingella kingae is a fastidious gram-negative coccobacillus that colonizes the respiratory and oropharyngeal tract in children. K. kingae occasionally causes invasive disease, primarily osteomyelitis/septic arthritis in young children, bacteremia in infants, and endocarditis in school-aged children and adults (1--8). Although diagnosis of this organism frequently is missed, invasive disease is uncommon. Only sporadic, non-epidemiologically linked cases have been reported. K. kingae constitutes part of the normal respiratory flora in children but can cause isolated cases of invasive disease, primarily osteomyelitis/septic arthritis (65%--75% of cases) in young children and bacteremia (20%--30% of cases) in infants (1,2,7,8). The majority of children who have invasive disease are previously healthy without immunosuppressive conditions; >90% are aged <2 years (1,2,5-8). Invasive disease is associated frequently with concomitant or precedent URI or stomatitis (3,4); disrupted respiratory or buccal mucosa might facilitate bacterial invasion and hematogenous dissemination. Biting might be an alternative means of introducing oropharyngeal pathogens into the bloodstream. The presence of K. kingae is difficult to detect without immediate clinical suspicion. Gram stain of synovial fluid shows WBCs but frequently is negative for organisms. Recovery of the organism in culture is difficult because of its fastidious nature, and might require laboratories to hold culture plates for up to 7 days. For cases described in this report, cultures were held longer than routine laboratory protocol recommends (usually 3 days) because an atypical organism was suspected. Studies of cases in Israel indicate that 40%--50% of culture-negative septic arthritis cases in children aged <2 years might be attributable to K. kingae (5,8). Inoculating synovial fluid or bony exudates directly into blood-culture bottles with a continuous monitoring system increases the rate of K. kingae recovery substantially, compared with direct plating of specimens on solid media (5,8). The increased awareness and enhanced capability of laboratories to isolate this organism might lead to an observed increase in incidence of K. kingae invasive disease. Although limited data are available about the epidemiology and transmission of K. kingae, the organism most likely is transmitted through respiratory secretions and saliva. In one study of an Israeli day care center, the monthly prevalence of K. kingae colonization ranged from 6% to 35%, and approximately 70% of children were colonized at some point during the 11-month study period. No invasive disease was observed (9). Subtyping by PFGE, immunoblotting, and ribotyping of the isolates demonstrated that children were colonized continuously, or intermittently with different subtypes over weeks to months. Two distinct subtypes with temporal clustering represented approximately 75% of the isolates (10). In comparison, a cohort of epidemiologically unrelated cases showed substantially more subtype variability (10). These findings suggest person-to-person transmission within the facility.	Kingella Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Kingella kingae is a fastidious gram-negative coccobacillus that colonizes the respiratory and oropharyngeal tract in children. K. kingae occasionally causes invasive disease, primarily osteomyelitis/septic arthritis in young children, bacteremia in infants, and endocarditis in school-aged children and adults (1--8). Although diagnosis of this organism frequently is missed, invasive disease is uncommon. Only sporadic, non-epidemiologically linked cases have been reported. K. kingae constitutes part of the normal respiratory flora in children but can cause isolated cases of invasive disease, primarily osteomyelitis/septic arthritis (65%--75% of cases) in young children and bacteremia (20%--30% of cases) in infants (1,2,7,8). The majority of children who have invasive disease are previously healthy without immunosuppressive conditions; >90% are aged <2 years (1,2,5-8). Invasive disease is associated frequently with concomitant or precedent URI or stomatitis (3,4); disrupted respiratory or buccal mucosa might facilitate bacterial invasion and hematogenous dissemination. Biting might be an alternative means of introducing oropharyngeal pathogens into the bloodstream. The presence of K. kingae is difficult to detect without immediate clinical suspicion. Gram stain of synovial fluid shows WBCs but frequently is negative for organisms. Recovery of the organism in culture is difficult because of its fastidious nature, and might require laboratories to hold culture plates for up to 7 days. For cases described in this report, cultures were held longer than routine laboratory protocol recommends (usually 3 days) because an atypical organism was suspected. Studies of cases in Israel indicate that 40%--50% of culture-negative septic arthritis cases in children aged <2 years might be attributable to K. kingae (5,8). Inoculating synovial fluid or bony exudates directly into blood-culture bottles with a continuous monitoring system increases the rate of K. kingae recovery substantially, compared with direct plating of specimens on solid media (5,8). The increased awareness and enhanced capability of laboratories to isolate this organism might lead to an observed increase in incidence of K. kingae invasive disease. Although limited data are available about the epidemiology and transmission of K. kingae, the organism most likely is transmitted through respiratory secretions and saliva. In one study of an Israeli day care center, the monthly prevalence of K. kingae colonization ranged from 6% to 35%, and approximately 70% of children were colonized at some point during the 11-month study period. No invasive disease was observed (9). Subtyping by PFGE, immunoblotting, and ribotyping of the isolates demonstrated that children were colonized continuously, or intermittently with different subtypes over weeks to months. Two distinct subtypes with temporal clustering represented approximately 75% of the isolates (10). In comparison, a cohort of epidemiologically unrelated cases showed substantially more subtype variability (10). These findings suggest person-to-person transmission within the facility.	https://www.wikidoc.org/index.php/Kingella
18c0cef492a58e00a88cdc29a13ed467911bb12b	wikidoc	Kola nut	Kola nut Kola nut (Cola) is a genus of about 125 species of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae (or treated in the separate family Sterculiaceae). It is related to the South American genus Theobroma (Cacao). They are evergreen trees, growing to 20 m tall, with glossy ovoid leaves up to 30 cm long. # Uses The kola nut has a bitter flavor and caffeine content, and is chewed in many West African cultures, individually or in a group setting. It is often used ceremonially, presented to tribal chiefs or presented to guests. Chewing kola nut can ease hunger pangs. Frequent chewing of the kola nut can also lead to stained teeth. Among the urban youth of West Africa, kola nut is becoming less popular. Kola was originally used to make cola soft drinks, though today most of these mass-produced beverages use artificial flavourings. Some exceptions are Barr's Red Kola, Harboe Original Taste Cola, Foxon Park Kola, Blue Sky Organic Cola, Sprecher's Puma Kola, and Cricket Cola, the latter being made from kola nuts and green tea. In 2007, United Kingdom supermarket Tesco introduced an American Premium Cola that uses kola nuts, spices and vanilla. The emerging energy drink mix, Blow, contains 50mg of kola nut extract per vial (in addition to 240mg of caffeine per serving). Outside of Africa, some species are cultivated for their nuts in Indonesia, Brazil, Jamaica and elsewhere in the humid tropics. Kola nuts are often used to treat whooping cough and asthma. The caffeine present acts as a bronchodilator, expanding the bronchial air passages. # Pharmacological Effects Kola nuts are used mainly for their stimulant and euphoriant qualities. They have effects similar to other xanthine containing herbs like cocoa, tea, coffee, guarana and yerba maté. However, the effects are distinctively different, producing a stronger state of euphoria and well being. They have stimulant effects on the central nervous system and heart. Animal experiments indicate that kola nuts have analeptic and lipolytic (fat-burning) properties, and stimulate the secretion of gastric juices. Human studies show kola nuts have positive chronotropic and weak diuretic effects. In humans it enhances alertness and physical energy, elevates mood, increases tactile sensitivity, suppresses the appetite and is used in Africa as an aphrodisiac. Autonomic changes include increased body temperature, increased blood pressure and increased respiratory rate. Effects may last up to 6 hours after ingestion. # Chemical Composition - caffeine (2- 3.5 %) - theobromine (1.0-2.5%) - theophylline - catechine - epicatechine - D-catechine - phenolics - phlobaphens - Kola red - betaine - protein - starch - fat - thiamine - riboflavin - niacin - ascorbic acid - betaine - sugar - gum - cellulose - water - calcium - potassium - iron - beta-carotene - tannic acid # Safety issues Kola nuts contain high amounts of N-nitroso compounds which are carcinogenic. In Nigeria, where the chewing of Kola nuts is a common practice, there is a high incidence of oral and gastrointestinal cancer which may be related to this habit. # History The use of the kola nut, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many West African cultures, individually or in a social setting, to restore vitality and ease hunger pangs. In 1911, kola became the focus of one of the earliest documented health scares when the US government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee, alleging that the caffeine in its drink was "injurious to health". On March 13, 1911, the government initiated the United States v. Forty Barrels and Twenty Kegs of Coca-Cola, hoping to force Coca-Cola to remove caffeine from its formula by making exaggerated claims, such as that the excessive use of Coca-Cola at one girls' school led to "wild nocturnal freaks, violations of college rules and female proprieties, and even immoralities." Although the judge ruled in favor of Coca-Cola, two bills were introduced to the U.S. House of Representatives in 1912 to amend the Pure Food and Drug Act, adding caffeine to the list of "habit-forming" and "deleterious" substances which must be listed on a product's label. # Literary References Ceremonial sharing of the kola nut plays an important role in Chinua Achebe's 1959 novel Things Fall Apart. In the movie "Tears of the Sun", the refugees give the SEALs a drink with Kola Nut to help them stay awake. In Dorothy Dunnett's "House of Niccolo" series, Nicholas de Fluery samples the kola nut often in his adventures in Africa.	Kola nut Kola nut (Cola) is a genus of about 125 species of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae (or treated in the separate family Sterculiaceae). It is related to the South American genus Theobroma (Cacao). They are evergreen trees, growing to 20 m tall, with glossy ovoid leaves up to 30 cm long. # Uses The kola nut has a bitter flavor and caffeine content, and is chewed in many West African cultures, individually or in a group setting. It is often used ceremonially, presented to tribal chiefs or presented to guests. Chewing kola nut can ease hunger pangs. Frequent chewing of the kola nut can also lead to stained teeth. Among the urban youth of West Africa, kola nut is becoming less popular. Kola was originally used to make cola soft drinks, though today most of these mass-produced beverages use artificial flavourings. Some exceptions are Barr's Red Kola, Harboe Original Taste Cola, Foxon Park Kola, Blue Sky Organic Cola, Sprecher's Puma Kola, and Cricket Cola, the latter being made from kola nuts and green tea. In 2007, United Kingdom supermarket Tesco introduced an American Premium Cola that uses kola nuts, spices and vanilla. The emerging energy drink mix, Blow, contains 50mg of kola nut extract per vial (in addition to 240mg of caffeine per serving). Outside of Africa, some species are cultivated for their nuts in Indonesia, Brazil, Jamaica and elsewhere in the humid tropics. Kola nuts are often used to treat whooping cough and asthma. The caffeine present acts as a bronchodilator, expanding the bronchial air passages. # Pharmacological Effects Kola nuts are used mainly for their stimulant and euphoriant qualities. They have effects similar to other xanthine containing herbs like cocoa, tea, coffee, guarana and yerba maté. However, the effects are distinctively different, producing a stronger state of euphoria and well being. They have stimulant effects on the central nervous system and heart. Animal experiments indicate that kola nuts have analeptic and lipolytic (fat-burning) properties, and stimulate the secretion of gastric juices. Human studies show kola nuts have positive chronotropic and weak diuretic effects. In humans it enhances alertness and physical energy, elevates mood, increases tactile sensitivity, suppresses the appetite and is used in Africa as an aphrodisiac. Autonomic changes include increased body temperature, increased blood pressure and increased respiratory rate. Effects may last up to 6 hours after ingestion. # Chemical Composition - caffeine (2- 3.5 %) - theobromine (1.0-2.5%) - theophylline - catechine - epicatechine - D-catechine - phenolics - phlobaphens - Kola red - betaine - protein - starch - fat - thiamine - riboflavin - niacin - ascorbic acid - betaine - sugar - gum - cellulose - water - calcium - potassium - iron - beta-carotene - tannic acid # Safety issues Kola nuts contain high amounts of N-nitroso compounds which are carcinogenic. In Nigeria, where the chewing of Kola nuts is a common practice, there is a high incidence of oral and gastrointestinal cancer which may be related to this habit. # History The use of the kola nut, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many West African cultures, individually or in a social setting, to restore vitality and ease hunger pangs. In 1911, kola became the focus of one of the earliest documented health scares when the US government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee, alleging that the caffeine in its drink was "injurious to health". On March 13, 1911, the government initiated the United States v. Forty Barrels and Twenty Kegs of Coca-Cola, hoping to force Coca-Cola to remove caffeine from its formula by making exaggerated claims, such as that the excessive use of Coca-Cola at one girls' school led to "wild nocturnal freaks, violations of college rules and female proprieties, and even immoralities." Although the judge ruled in favor of Coca-Cola, two bills were introduced to the U.S. House of Representatives in 1912 to amend the Pure Food and Drug Act, adding caffeine to the list of "habit-forming" and "deleterious" substances which must be listed on a product's label. # Literary References Ceremonial sharing of the kola nut plays an important role in Chinua Achebe's 1959 novel Things Fall Apart. In the movie "Tears of the Sun", the refugees give the SEALs a drink with Kola Nut to help them stay awake. In Dorothy Dunnett's "House of Niccolo" series, Nicholas de Fluery samples the kola nut often in his adventures in Africa.	https://www.wikidoc.org/index.php/Kola_nut
a8865b40d09617fabb896bbed2d927bcabdb2136	wikidoc	Kombucha	Kombucha Kombucha is the Western name for sweetened tea or tisane that has been fermented by a macroscopic solid mass of microorganisms called a "kombucha colony," usually consisting principally of Bacterium xylinum and yeast cultures. It has gained much popular support within many communities, mentioned by talk show hosts and celebrities. The increase in popularity can be seen by the many commercial brands coming onto the retail market and thousands of web pages about this fermented beverage. # Biology of kombucha The culture contains a symbiosis of yeast species and acetic acid bacteria, mostly Bacterium xylinum. Species of yeast involved vary, and may include: Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii. The culture itself looks somewhat like a large pancake, and though often called a mushroom, or by the acronym SCOBY (for "Symbiotic Colony of Bacteria and Yeast"), it is clinically known as a zoogleal mat. # History and etymology The recorded history of this drink dates back to the Qin Dynasty in China (around 250 BC). The Chinese called it the "Immortal Health Elixir," because they believed Kombucha balanced the Middle Qi (Spleen and Stomach) and aided in digestion, allowing the body to focus on healing. Knowledge of kombucha eventually reached Russia and then Eastern Europe around the Early Modern Age, when tea first became affordable by the populace. The word kombucha, while sounding Japanese to foreign ears, is a misnomer when applied to this beverage. In fact, Kombucha (昆布茶) in Japanese refers to a tea-like infusion (cha) (actually, more of a thin soup) made from kelp (kombu), usually served to patients in convalescence. The Japanese refer to 'kombucha' as kōcha-kinoko (紅茶キノコ), which literally means black tea mushroom. ## Russian "tea mushroom" The process of brewing kombucha was introduced in Russia and the Ukraine at the end of the 1800s, and became popular in the early 1900s. The kombucha culture is known locally as chayniy grib, (чайный гриб - 'tea mushroom'), and the drink itself is referred to as grib (гриб - 'mushroom'), "tea kvass" or simply "kvass", although it differs from regular "kvass" which is not made from tea and is generally fermented only with yeast and not the other bacteria which ferment tea to form kombucha. # Components Kombucha contains many different cultures along with several organic acids, active enzymes, amino acids, anti-oxidants, and polyphenols. For the home brewer, there is no way to know the amounts of the components unless a sample is sent to a laboratory. The US Food and Drug Administration has no findings on the effects of kombucha. Each strain of kombucha may contain some of the following components depending on the source of the culture: Acetic acid, which mainly inhibits harmful bacteria and so is used as a preservative. It is also what gives Kombucha that 'kick' to its smell and taste. Butyric acid, produced by the yeasts and when working with gluconic acid, and in help combat yeast infections such as candida. Gluconic acid, effective against many yeast infections such as candidiasis and thrush. Lactic acid, found in kombucha in its most potent form, L-lactic(+). Malic acid, also used in the body's detoxification process. Oxalic acid, encourages the cellular production of energy and is a natural preservative. Usnic acid, a potent antibiotic that exhibits antiviral, antiprotozoal, antimitotic, anti-inflammatory and analgesic activity. Kombucha also contains vitamin groups B and C, beneficial yeasts and bacteria. # Health effects No clinical studies have been performed that demonstrate any specific curative properties of kombucha. A review of the published literature on the safety of kombucha suggests no specific oral toxicity in rats, although other reports suggest that care should be taken in humans when combined with medical drugs, hormone replacement therapy, etc. It may also cause allergic reactions or other complications, and one should discontinue use or consult a medical professional if complications arise. Advocates believe kombucha works by assisting in the phase II liver detoxification pathway, leading to efficient elimination of endogenous and exogenous bodily wastes. This hypothesis is due to the observation of increased glucuronic acid conjugates in the urine after kombucha consumption. Early chemical analysis of kombucha brew suggested that glucuronic acid was a key component of it, perhaps assisting the liver by supplying more of the substance during detoxification. But more recent analysis of kombucha offer a different explanation, as outlined in the book in Analysis of Kombucha Ferments by Michael Roussin. Roussin reports on an extensive chemical analysis of a variety of commercial and homebrew versions of kombucha, and finds no evidence of glucuronic acid at any concentration. But Roussin suggests that another component may have health benefits: D - glucaro -1,4 lactone, also known as glucaric acid. It serves as an inhibitor of the beta- glucuronidase enzyme, a bacterial product from the gut microbiota that can cleave the glucuronic acid conjugates and send bodily wastes back into circulation, thus increasing the exposure time before the waste is ultimately excreted. Therefore, the active component of kombucha likely exerts its effect by preventing bacterial disruption of glucuronic acid conjugates and increasing the detoxification efficiency of the liver. Glucaric acid is being explored independently as a cancer preventive agent. Reports of adverse reactions may be related to unsanitary fermentation conditions, leaching of compounds from the fermentation vessels, or "sickly" kombucha cultures that cannot acidify the brew. Cleanliness is important during preparation, and in most cases, the acidity of the fermented drink prevents growth of unwanted contaminants. If a culture becomes contaminated, it will most likely be seen as common mold, green or brown in color. # Preparation There are many ways to prepare kombucha. Though kombucha is almost always prepared with sugar and tea, almost any beverage containing sugar and caffeine (such as cola or sweetened coffee) will allow the culture to grow, though the resultant beverage may be quite unpalatable. Many brewers also recommend using organic ingredients wherever possible to prevent the addition of unwanted chemicals and preservatives. In one method, the beverage is made by placing some existing kombucha culture in a jar, usually a 3 liter glass container, then pouring in cold black tea with sugar. In about 8-12 days, the first portion of the beverage is ready; part of it is removed for consumption, and more tea with sugar is added to fill the jar. A mature kombucha is several centimeters thick and produces a portion of beverage every day. As the kombucha slowly grows, from time to time slices are taken off it, which can be used to start new cultures in separate containers. Another method allows for the bottling and saving of kombucha for later consumption. As in the previous method, the culture is placed into a large glass jar and the tea is added. The jar is covered with a coffee filter or paper towel secured with string or rubber bands, and left for seven or eight days. Part of the kombucha is poured off into glass jars and refrigerated for a few days, while part is kept back to start a new batch. The refrigeration allows the flavor to deepen, and the natural carbonation to build up. Each time the kombucha culture goes through the fermentation process, it creates one new "mushroom" layer, or zoogleal mat, which will form atop of the original. After three or four layers have built up, the tea will become sour and taste somewhat like vinegar. When the new batch is ready, one may either use the second layer to start another batch, along with the original one for its own batch or it may be thrown away. Each culture can be used over and over again but most people discard an older one and use the newer to make their next batch of tea. # Safety and contamination As with all foods, care must be taken during preparation and storage to prevent contamination. Keeping the kombucha brew safe and contamination-free is a concern to many home brewers and the FDA. Key components of food safety when brewing kombucha include clean environment, proper temperature, and low pH. In every step of the preparation process, it is important that hands and utensils (anything that is going to come into contact with the culture) are dish soap clean so as not to contaminate the kombucha. For safety reasons, Kombucha should be brewed in food-grade glass containers only. Kombucha should not be brewed in lead crystal, ceramic, plastic, painted, or metallic containers including stainless steel, as the acidic solution can leach by-products into the finished product. Keeping cultures covered and in a clean environment also reduces the risk of introducing contaminants and bacteria. Kombucha grows best in a warm place (about 80°F / 27°C) and out of direct sunlight. Optimum conditions ensure speedy maturation, reducing risk for contamination. Maintaining a correct pH is an important factor in a home-brew. Acidic conditions are favorable for the growth of the kombucha culture, and inhibit the growth of molds and bacteria. The pH of the kombucha batch should be between 2.5 and 4.5. A pH of less than 2.5 makes the drink too acidic for human consumption, while a pH greater than 4.5 increases the risk of contamination. Use of fresh "starter tea" and/or vinegar can be used to control pH. Some brewers test the pH at the beginning and the end of the brewing cycle to ensure that the correct pH is achieved. If mold does grow on the surface of the kombucha pellicle, or "mushroom," it is best to throw out the batch and start over. # Additional subjective effects Aside from any possible health benefits, many users report a subtle but definite perceptual shift after consuming kombucha. It is generally characterized by mild euphoria, relaxation, and an overall sense of physical and mental well-being. This effect is not to be confused with the highs associated with some illegal drugs. Kombucha contains trace amounts of alcohol and caffeine, unless made with decaffeinated tea. Alcohol amounts vary from 0.5% to 1.7% depending on brewing time and amounts of sugar used in the fermentation of the tea which may account for the experiencing of these effects by some consumers. Another possible cause of these effects is the psychoactive amino acid L-theanine, which is naturally present in tea. Stimulation of the circulatory and immune systems, and associated glandular releases, may also account for some of these effects. # Trivia - Chef Josef Desimone of Google makes kombucha for Google employees. Almost 100 glasses of kombucha are served every day at Google cafeterias. - The popular alternative metal band System of a Down references kombucha in the song "Sugar" on their self-titled album. Lead vocalist Serj Tankian screams, "The kombucha mushroom people sitting around all day." - Singer-songwriter and guitarist M. Ward listed kombucha as his "best purchase of the past year" in 2006, stating that "It's an acquired taste, but they tell me it rejuvenates, restores, revitalizes and replenishes." - On an episode of MTV Cribs featuring the home of surfer Laird Hamilton and volleyball player and model Gabrielle Reece, their refrigerator opened to reveal several bottles of "Kombucha Wonder Drink," a bottled tea drink containing kombucha. Reece removed a bottle and displayed it to the camera, stating that kombucha is "a very good healthy drink, it helps support mental health and gives energy." - Lindsay Lohan has been spotted drinking kombucha after leaving rehab.	Kombucha Kombucha is the Western name for sweetened tea or tisane that has been fermented by a macroscopic solid mass of microorganisms called a "kombucha colony," usually consisting principally of Bacterium xylinum and yeast cultures. It has gained much popular support within many communities, mentioned by talk show hosts and celebrities. The increase in popularity can be seen by the many commercial brands coming onto the retail market and thousands of web pages about this fermented beverage. # Biology of kombucha The culture contains a symbiosis of yeast species and acetic acid bacteria, mostly Bacterium xylinum. Species of yeast involved vary, and may include: Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii. The culture itself looks somewhat like a large pancake, and though often called a mushroom, or by the acronym SCOBY (for "Symbiotic Colony of Bacteria and Yeast"), it is clinically known as a zoogleal mat. # History and etymology The recorded history of this drink dates back to the Qin Dynasty in China (around 250 BC). The Chinese called it the "Immortal Health Elixir," because they believed Kombucha balanced the Middle Qi (Spleen and Stomach) and aided in digestion, allowing the body to focus on healing.[citation needed] Knowledge of kombucha eventually reached Russia and then Eastern Europe around the Early Modern Age, when tea first became affordable by the populace. The word kombucha, while sounding Japanese to foreign ears, is a misnomer when applied to this beverage. In fact, Kombucha (昆布茶) in Japanese refers to a tea-like infusion (cha) (actually, more of a thin soup) made from kelp (kombu), usually served to patients in convalescence. The Japanese refer to 'kombucha' as kōcha-kinoko (紅茶キノコ), which literally means black tea mushroom. ## Russian "tea mushroom" The process of brewing kombucha was introduced in Russia and the Ukraine at the end of the 1800s, and became popular in the early 1900s. The kombucha culture is known locally as chayniy grib, (чайный гриб - 'tea mushroom'), and the drink itself is referred to as grib (гриб - 'mushroom'), "tea kvass" or simply "kvass", although it differs from regular "kvass" which is not made from tea and is generally fermented only with yeast and not the other bacteria which ferment tea to form kombucha. # Components Kombucha contains many different cultures along with several organic acids, active enzymes, amino acids, anti-oxidants, and polyphenols. For the home brewer, there is no way to know the amounts of the components unless a sample is sent to a laboratory. The US Food and Drug Administration has no findings on the effects of kombucha. Each strain of kombucha may contain some of the following components depending on the source of the culture: Acetic acid, which mainly inhibits harmful bacteria and so is used as a preservative. It is also what gives Kombucha that 'kick' to its smell and taste. Butyric acid, produced by the yeasts and when working with gluconic acid, and in help combat yeast infections such as candida. Gluconic acid, effective against many yeast infections such as candidiasis and thrush. Lactic acid, found in kombucha in its most potent form, L-lactic(+). Malic acid, also used in the body's detoxification process. Oxalic acid, encourages the cellular production of energy and is a natural preservative. Usnic acid, a potent antibiotic that exhibits antiviral, antiprotozoal, antimitotic, anti-inflammatory and analgesic activity. Kombucha also contains vitamin groups B and C, beneficial yeasts and bacteria. # Health effects No clinical studies have been performed that demonstrate any specific curative properties of kombucha. A review of the published literature on the safety of kombucha suggests no specific oral toxicity in rats[1], although other reports suggest that care should be taken in humans when combined with medical drugs, hormone replacement therapy, etc.[2] It may also cause allergic reactions or other complications, and one should discontinue use or consult a medical professional if complications arise.[3] Advocates believe kombucha works by assisting in the phase II liver detoxification pathway, leading to efficient elimination of endogenous and exogenous bodily wastes. This hypothesis is due to the observation of increased glucuronic acid conjugates in the urine after kombucha consumption. Early chemical analysis of kombucha brew suggested that glucuronic acid was a key component of it, perhaps assisting the liver by supplying more of the substance during detoxification. But more recent analysis of kombucha offer a different explanation, as outlined in the book in Analysis of Kombucha Ferments by Michael Roussin.[4] Roussin reports on an extensive chemical analysis of a variety of commercial and homebrew versions of kombucha, and finds no evidence of glucuronic acid at any concentration. But Roussin suggests that another component may have health benefits: D - glucaro -1,4 lactone, also known as glucaric acid. It serves as an inhibitor of the beta- glucuronidase enzyme, a bacterial product from the gut microbiota that can cleave the glucuronic acid conjugates and send bodily wastes back into circulation, thus increasing the exposure time before the waste is ultimately excreted. Therefore, the active component of kombucha likely exerts its effect by preventing bacterial disruption of glucuronic acid conjugates and increasing the detoxification efficiency of the liver. Glucaric acid is being explored independently as a cancer preventive agent.[5] Reports of adverse reactions may be related to unsanitary fermentation conditions, leaching of compounds from the fermentation vessels,[6] or "sickly" kombucha cultures that cannot acidify the brew. Cleanliness is important during preparation, and in most cases, the acidity of the fermented drink prevents growth of unwanted contaminants. If a culture becomes contaminated, it will most likely be seen as common mold, green or brown in color.[7] # Preparation There are many ways to prepare kombucha. Though kombucha is almost always prepared with sugar and tea, almost any beverage containing sugar and caffeine (such as cola or sweetened coffee) will allow the culture to grow, though the resultant beverage may be quite unpalatable. Many brewers also recommend using organic ingredients wherever possible to prevent the addition of unwanted chemicals and preservatives. In one method, the beverage is made by placing some existing kombucha culture in a jar, usually a 3 liter glass container, then pouring in cold black tea with sugar. In about 8-12 days, the first portion of the beverage is ready; part of it is removed for consumption, and more tea with sugar is added to fill the jar. A mature kombucha is several centimeters thick and produces a portion of beverage every day. As the kombucha slowly grows, from time to time slices are taken off it, which can be used to start new cultures in separate containers. Another method allows for the bottling and saving of kombucha for later consumption. As in the previous method, the culture is placed into a large glass jar and the tea is added. The jar is covered with a coffee filter or paper towel secured with string or rubber bands, and left for seven or eight days. Part of the kombucha is poured off into glass jars and refrigerated for a few days, while part is kept back to start a new batch. The refrigeration allows the flavor to deepen, and the natural carbonation to build up. Each time the kombucha culture goes through the fermentation process, it creates one new "mushroom" layer, or zoogleal mat, which will form atop of the original. After three or four layers have built up, the tea will become sour and taste somewhat like vinegar. When the new batch is ready, one may either use the second layer to start another batch, along with the original one for its own batch or it may be thrown away. Each culture can be used over and over again but most people discard an older one and use the newer to make their next batch of tea. # Safety and contamination As with all foods, care must be taken during preparation and storage to prevent contamination. Keeping the kombucha brew safe and contamination-free is a concern to many home brewers and the FDA. Key components of food safety when brewing kombucha include clean environment, proper temperature, and low pH. In every step of the preparation process, it is important that hands and utensils (anything that is going to come into contact with the culture) are dish soap clean so as not to contaminate the kombucha. For safety reasons, Kombucha should be brewed in food-grade glass containers only. Kombucha should not be brewed in lead crystal, ceramic, plastic, painted, or metallic containers including stainless steel, as the acidic solution can leach by-products into the finished product.[1] Keeping cultures covered and in a clean environment also reduces the risk of introducing contaminants and bacteria. Kombucha grows best in a warm place (about 80°F / 27°C) and out of direct sunlight. Optimum conditions ensure speedy maturation, reducing risk for contamination. Maintaining a correct pH is an important factor in a home-brew. Acidic conditions are favorable for the growth of the kombucha culture, and inhibit the growth of molds and bacteria. The pH of the kombucha batch should be between 2.5 and 4.5. A pH of less than 2.5 makes the drink too acidic for human consumption, while a pH greater than 4.5 increases the risk of contamination. Use of fresh "starter tea" and/or vinegar can be used to control pH. Some brewers test the pH at the beginning and the end of the brewing cycle to ensure that the correct pH is achieved.[8] If mold does grow on the surface of the kombucha pellicle, or "mushroom," it is best to throw out the batch and start over. # Additional subjective effects Aside from any possible health benefits, many users report a subtle but definite perceptual shift after consuming kombucha. It is generally characterized by mild euphoria, relaxation, and an overall sense of physical and mental well-being. This effect is not to be confused with the highs associated with some illegal drugs. Kombucha contains trace amounts of alcohol and caffeine, unless made with decaffeinated tea. Alcohol amounts vary from 0.5% to 1.7% depending on brewing time and amounts of sugar used in the fermentation of the tea which may account for the experiencing of these effects by some consumers. Another possible cause of these effects is the psychoactive amino acid L-theanine, which is naturally present in tea. Stimulation of the circulatory and immune systems, and associated glandular releases, may also account for some of these effects. # Trivia - Chef Josef Desimone of Google makes kombucha for Google employees. Almost 100 glasses of kombucha are served every day at Google cafeterias. - The popular alternative metal band System of a Down references kombucha in the song "Sugar" on their self-titled album. Lead vocalist Serj Tankian screams, "The kombucha mushroom people sitting around all day." - Singer-songwriter and guitarist M. Ward listed kombucha as his "best purchase of the past year" in 2006, stating that "It's an acquired taste, but they tell me it rejuvenates, restores, revitalizes and replenishes." [9] - On an episode of MTV Cribs featuring the home of surfer Laird Hamilton and volleyball player and model Gabrielle Reece, their refrigerator opened to reveal several bottles of "Kombucha Wonder Drink," a bottled tea drink containing kombucha. Reece removed a bottle and displayed it to the camera, stating that kombucha is "a very good healthy drink, it helps support mental health and gives energy."[10] - Lindsay Lohan has been spotted drinking kombucha after leaving rehab.[11]	https://www.wikidoc.org/index.php/Kombucha
0cac053144525868f8074d113d7c45ca5ee4bf55	wikidoc	Tyrosine	Tyrosine # Overview Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cells to synthesize proteins. This is a non-essential amino acid and it is found in large quantities in casein. In fact, the word "tyrosine" is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. # Functions Aside from being a proteogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes. It functions as a receiver of phosphate groups that are transferred by way of protein kinases (so-called receptor tyrosine kinases). Phosphorylation of the hydroxyl group changes the activity of the target protein. A tyrosine residue also plays an important role in photosynthesis. In chloroplasts (photosystem II), it acts as an electron donor in the reduction of oxidized chlorophyll. In this process, it undergoes deprotonation of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese cluster. # Biosynthesis In plants and most microorganisms, tyr is produced via prephenate, an intermediate on the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate. Mammals synthesize tyrosine from the essential amino acid phenylalanine (phe), which is derived from food. The conversion of phe to tyr is catalyzed by the enzyme phenylalanine hydroxylase, a monooxygenase. This enzyme catalyzes the reaction causing the addition of an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. # Metabolism ## Phosphorylation and sulfation Some of the tyrosine residues can be tagged with a phosphate group (phosphorylated) by protein kinases. (In its phosphorylated state, it is referred to as phosphotyrosine). Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine. ## Precursor to hormones In the adrenal gland, tyrosine is converted to levodopa by the enzyme tyrosine hydroxylase (TH). TH is also the rate-limiting enzyme involved in the synthesis of the catecholamine hormones dopamine, norepinephrine (noradrenaline), and epinephrine. The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid also are derived from tyrosine. ## Precursor to alkaloids In Papaver somniferum, the opium poppy, tyrosine is used to produce the alkaloid morphine. ## Precursor to pigments Tyrosine is also the precursor to the pigment melanin. ## Degradation The decomposition of L-tyrosine (syn. para-hydroxyphenylalanine) begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other (see the illustration below). The next oxidation step catalyzes by p-hydroxylphenylpyruvate-dioxygenase and splitting off CO2 homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate is created. Fumarylacetate is created maleylacetoacetate-cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally split via fumarylacetoacetate-hydrolase through the addition of a water molecule. Thereby fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis. # Ortho- and meta-tyrosine Three isomers of tyrosine are known. In addition to common amino acid L-tyrosine which is the para isomer (para-tyr, p-tyr or 4-hydroxyphenylalanine) there are two additional regioisomers, namely meta-tyrosine (m-tyr or 3-hydroxyphenylalanine or L-m-tyrosine) and ortho-tyrosine (o-tyr or 2-hydroxyphenylalanine) which occur in nature. The m-tyr and o-tyr isomers, which are rare, arise through non-enzymatic free-radical hydroxylation of phenylalanine under conditions of oxidative stress. m-Tyrosine and analogues (rare in nature and therefore available synthetically) have shown application in Parkinson's Disease, Alzheimer's disease and arthritis . # Medical use Tyrosine is a starting material for neurotransmitters and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine) but has little if any effect on mood. The effect on mood is more noticeable in humans subjected to stressful conditions (see below). A number of studies have found tyrosine to be useful during conditions of stress, cold, fatigue, prolonged work and sleep deprivation, with reductions in stress hormone levels, reductions in stress-induced weight loss seen in animal trials, improvements in cognitive and physical performance seen in human trials. Tyrosine does not seem to have any significant effect on mood, cognitive or physical performance in normal circumstances. A daily dosage supported in the literature is about 100 mg/kg for an adult. The usual dosage amounts to 500-1500 mg per day (dose suggested by most manufacturers; usually an equivalent to 1-3 capsules of pure tyrosine). It is not recommended to exceed 12000 mg (12 g) per day. In fact, too high doses result in reduced levels of dopamine.	Tyrosine Template:NatOrganicBox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Tyrosine (abbreviated as Tyr or Y)[1] or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cells to synthesize proteins. This is a non-essential amino acid and it is found in large quantities in casein. In fact, the word "tyrosine" is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese.[2][3] # Functions Aside from being a proteogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes. It functions as a receiver of phosphate groups that are transferred by way of protein kinases (so-called receptor tyrosine kinases). Phosphorylation of the hydroxyl group changes the activity of the target protein. A tyrosine residue also plays an important role in photosynthesis. In chloroplasts (photosystem II), it acts as an electron donor in the reduction of oxidized chlorophyll. In this process, it undergoes deprotonation of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese cluster. # Biosynthesis In plants and most microorganisms, tyr is produced via prephenate, an intermediate on the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate. Mammals synthesize tyrosine from the essential amino acid phenylalanine (phe), which is derived from food. The conversion of phe to tyr is catalyzed by the enzyme phenylalanine hydroxylase, a monooxygenase. This enzyme catalyzes the reaction causing the addition of an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. # Metabolism ## Phosphorylation and sulfation Some of the tyrosine residues can be tagged with a phosphate group (phosphorylated) by protein kinases. (In its phosphorylated state, it is referred to as phosphotyrosine). Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation.[4] Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine. ## Precursor to hormones In the adrenal gland, tyrosine is converted to levodopa by the enzyme tyrosine hydroxylase (TH). TH is also the rate-limiting enzyme involved in the synthesis of the catecholamine hormones dopamine, norepinephrine (noradrenaline), and epinephrine. The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid also are derived from tyrosine. ## Precursor to alkaloids In Papaver somniferum, the opium poppy, tyrosine is used to produce the alkaloid morphine. ## Precursor to pigments Tyrosine is also the precursor to the pigment melanin. ## Degradation The decomposition of L-tyrosine (syn. para-hydroxyphenylalanine) begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other (see the illustration below). The next oxidation step catalyzes by p-hydroxylphenylpyruvate-dioxygenase and splitting off CO2 homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate is created. Fumarylacetate is created maleylacetoacetate-cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally split via fumarylacetoacetate-hydrolase through the addition of a water molecule. Thereby fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis. # Ortho- and meta-tyrosine Three isomers of tyrosine are known. In addition to common amino acid L-tyrosine which is the para isomer (para-tyr, p-tyr or 4-hydroxyphenylalanine) there are two additional regioisomers, namely meta-tyrosine (m-tyr or 3-hydroxyphenylalanine or L-m-tyrosine) and ortho-tyrosine (o-tyr or 2-hydroxyphenylalanine) which occur in nature. The m-tyr and o-tyr isomers, which are rare, arise through non-enzymatic free-radical hydroxylation of phenylalanine under conditions of oxidative stress.[5][6] m-Tyrosine and analogues (rare in nature and therefore available synthetically) have shown application in Parkinson's Disease, Alzheimer's disease and arthritis [7]. # Medical use Tyrosine is a starting material for neurotransmitters and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine)[8] but has little if any effect on mood.[9][10][11] The effect on mood is more noticeable in humans subjected to stressful conditions (see below). A number of studies have found tyrosine to be useful during conditions of stress, cold, fatigue,[12] prolonged work and sleep deprivation,[13][14] with reductions in stress hormone levels,[15] reductions in stress-induced weight loss seen in animal trials,[12] improvements in cognitive and physical performance[10][16][17] seen in human trials. Tyrosine does not seem to have any significant effect on mood, cognitive or physical performance in normal circumstances.[18][19][20] A daily dosage supported in the literature is about 100 mg/kg for an adult. The usual dosage amounts to 500-1500 mg per day (dose suggested by most manufacturers; usually an equivalent to 1-3 capsules of pure tyrosine). It is not recommended to exceed 12000 mg (12 g) per day. In fact, too high doses result in reduced levels of dopamine.[18]	https://www.wikidoc.org/index.php/L-m-tyrosine
8b5e26d10bc0e90d9e44e764ffcf0ef907331f61	wikidoc	LGALS3BP	LGALS3BP Galectin-3-binding protein is a protein that in humans is encoded by the LGALS3BP gene. # Function The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell–cell and cell–matrix interactions. Using fluorescence in–situ hybridization, the full length 90K cDNA has been localized to chromosome 17q25. The native protein binds specifically to a human macrophage-associated lectin known as Mac-2 and also binds to galectin 1. # Clinical significance LGALS3BP has been found elevated in the serum of patients with cancer and in those infected by the human immunodeficiency virus (HIV). It appears to be implicated in immune response associated with natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity. # Interactions LGALS3BP has been shown to interact with LGALS3.	LGALS3BP Galectin-3-binding protein is a protein that in humans is encoded by the LGALS3BP gene.[1][2][3][4] # Function The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell–cell and cell–matrix interactions. Using fluorescence in–situ hybridization, the full length 90K cDNA has been localized to chromosome 17q25. The native protein binds specifically to a human macrophage-associated lectin known as Mac-2 and also binds to galectin 1.[4] # Clinical significance LGALS3BP has been found elevated in the serum of patients with cancer and in those infected by the human immunodeficiency virus (HIV). It appears to be implicated in immune response associated with natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity.[4] # Interactions LGALS3BP has been shown to interact with LGALS3.[3][5][6]	https://www.wikidoc.org/index.php/LGALS3BP
8ee105ff1e5e349c10edf0bb5a25c0f9449946fc	wikidoc	PAFAH1B1	PAFAH1B1 Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene. The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein. # Function PAFAH1B1 was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker syndrome. PAFAH1B1 encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. According to one study, PAFAH1B1 interacts with VLDLR receptor activated by reelin. # Genomics The gene is located at chromosome 17p13.3 on the Watson (plus) strand. The gene is 91,953 bases in length and encodes a protein of 410 amino acids (predicted molecular weight 46.638 kiloDaltons). # Interactions PAFAH1B1 has been shown to interact with DYNC1H1, CLIP1, NDEL1, NDE1, PAFAH1B3, PAFAH1B2, NUDC, TUBA1A and Doublecortin.	PAFAH1B1 Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene.[1][2][3] The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein.[4] # Function PAFAH1B1 was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker syndrome. PAFAH1B1 encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum.[3] According to one study, PAFAH1B1 interacts with VLDLR receptor activated by reelin.[5] # Genomics The gene is located at chromosome 17p13.3 on the Watson (plus) strand. The gene is 91,953 bases in length and encodes a protein of 410 amino acids (predicted molecular weight 46.638 kiloDaltons). # Interactions PAFAH1B1 has been shown to interact with DYNC1H1,[6] CLIP1,[7] NDEL1,[8][9] NDE1,[10] PAFAH1B3,[11] PAFAH1B2,[11] NUDC,[12] TUBA1A[13] and Doublecortin.[14]	https://www.wikidoc.org/index.php/LIS1
467cf9bf12d36498e2bf41243ed77ce67d0317d5	wikidoc	Lacritin	Lacritin Lacritin is a 12.3 kDa glycoprotein encoded in humans by the LACRT gene. Lacritin's discovery emerged from a screen for factors that stimulate tear protein secretion. Lacritin is a secreted protein found in tears and saliva. Lacritin also promotes tear secretion, the proliferation and survival of epithelial cells, and corneal wound healing Lacritin is thus a multifunctional prosecretory mitogen with cell survival activity. Natural or bacterial cleavage of lacritin releases a C-terminal fragment that is bactericidal. Most lacritin is produced by the lacrimal gland, including the accessory lacrimal gland of Wolfring. Some lacritin is produced by the meibomian gland, and by epithelial cells of the conjunctiva and cornea. Together these epithelia comprise much of the lacrimal functional unit (LFU). Dry eye is the most common disease of the LFU. A growing number of studies suggest that lacritin may be differentially downregulated in dry eye, including contact lens-related dry eye. Topical lacritin promotes tearing in rabbit preclinical studies. In the Aire knockout mouse model of dry eye (considered similar to human Sjogren's syndrome), topical lacritin restores pilocarpine-induced tearing, largely eliminates lissamine green staining and reduces the size of inflammatory foci in the lacrimal gland. Lacritin cell targeting is dependent on the cell surface heparan sulfate proteoglycan syndecan-1 (SDC1). Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein. A G-protein-coupled receptor (GPCR) then appears to be ligated. Targeted cells signal to NFAT and mTOR if conditions are suitable for proliferation, or to AKT and FOXO3 under conditions of stress. # Structure Lacritin consists of 119 amino acids after cleavage of the N-terminal signal peptide and displays several predicted alpha helices, mostly in the C-terminal half. Of these, the two C-terminal ones have been confirmed by circular dichroism. The most C-terminal alpha helix is amphipathic with hydrophobic and hydrophilic residues on opposite faces. The hydrophobic face is an important syndecan-1 binding element. PONDR (Predictor of Naturally Disordered Regions) predicts that the C-terminal and N-terminal halves are respectively 'ordered' and 'disordered'. 11 - 12 predicted O-glycosylation sites populate the N-terminal half. The C-terminal amphipathic alpha helix is also the site of lacritin's only N-glycosylation site. In 'climatic droplet keratopathy' this site is not glycosylated. Lacritin recombinantly generated in E. coli (no glycosylation) and lacritin in tears (glycosylated) differ in size with respective mobilities of ~18 and ~25 kDa by SDS-PAGE. With a predicted protein core molecular weight of 12.3 kDa, it is possible that mobility is partially retarded by lacritin's amphipathic alpha helices. Predicted pI of lacritin's core protein is 5. Lacritin is subject to crosslinking by tissue transglutaminase, thereby giving rise to lacritin multimers including dimers and trimers. Crosslinking is initiated within 1 min in vitro, requiring as little as 0.1 nM lacritin. The ~0.6 micro molar level of tissue transglutaminase estimated in human tears is sufficient to promote crosslinking. Crosslinking involves the donors lysine 82 and 85 and the acceptor glutamine 106. Glutamine 106 resides within the amphipathic alpha helix near the C-terminus responsible for binding the N-terminus of syndecan-1. Accordingly, crosslinked lacritin binds syndecan-1 poorly and is inactive. Several lacritin splice variants have been detected in Aceview, from NEIBank EST data. Lacritin-b (11.1 kDa; pI 5.3) lacks the sequence SIVEKSILTE. Lacritin-c (10.7 kDa; pI 4.6) displays a novel C-terminus that should be incapable of binding syndecan-1, and lacks cell survival activity. # Cell targeting Lacritin targets a restricted group of epithelial cells (including human corneal epithelia), and not fibroblastic, glioma, or lymphoblastic cells. Cell surface proteoglycan syndecan-1 is partly responsible. Biotinylated cell surface proteins from a lacritin-responsive cell were incubated with lacritin under conditions of physiological salt. Those that bound lacritin were sequenced by mass spectrometry. Few bound. The most prominent was syndecan-1 (SDC1). In confirmatory pull-down assays, binding was not shared with family members syndecan-2 or syndecan-4, indicating that the protein core (and not the negatively charged heparan sulfate side-chains) was the main site of binding. Further analysis narrowed the site to syndecan-1's N-terminal 51 amino acids, and subsequently to the N-terminal sequence GAGAL that is conserved in syndecan-1's from different species. GAGAL promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix and likely binds to the hydrophobic face. Syndecan-1 binds many growth factors through its long heparan sulfate side-chains. Yet, long heparan sulfate chains interfere with lacritin binding. Since syndecans are always decorated with heparan sulfate, this means that heparanase must be available to partially or completely cleave off heparan sulfate, allowing lacritin to bind. Indeed, no binding was detected from cells lacking heparanase after siRNA depletion. Binding was restored by spiking in exogenous heparanase or heparitinase. Thus, heparanase regulates lacritin function as an 'on-switch'. Exposed 3-O sulfated group(s) on heparanase-cleaved heparan sulfate (that likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix), and an N-terminal chondroitin sulfate chain (likely also binds to the cationic face) appear to contribute to binding. Point mutagenesis of lacritin has narrowed the ligation site. This novel heparanase mechanism appears at first glance to be poor for ocular health since heparanase release from invading lymphocytes in the corneal stroma is inflammatory. Yet heparanase is a normal secretory product of the corneal epithelium. Lacritin-dependent mitogenesis is inhibitable by pertussis toxin,. The implication is that another key element of lacritin targeting specificity is a G-protein-coupled receptor that would presumably form a cell surface targeting complex with SDC1. Involvement of a G-protein coupled receptor would explain the rapidity of lacritin signaling. # Function Lacritin is a glycoprotein of the human tear film, and to a lesser extent of saliva, lung lavage and plasma. It is mainly produced by the lacrimal gland. Some lacritin also is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea. The lacritin gene (LACRT) is one of the most transcriptionally regulated genes in the human eye. Functional studies suggest a role in epithelial renewal of some non-germative epithelia. By flowing downstream through ducts, it may generate a 'proliferative field'. Lacritin also promotes secretion (including that of lipocalin-1 and lactoferrin), cell survival and regeneration of the corneal epithelium after wounding. This raises the possibility that lacritin may have clinical applications in the treatment of dry eye, the most common eye disease. It also may be beneficial in promoting healing after LASIK or PRK surgery. Recent studies suggest that lacritin monomer is differentially down regulated in not only in dry eye, but also in blepharitis. Lacritin is an LFU prosecretory mitogen and survival factor with a biphasic dose response that is optimal at 1 - 10 nM for human recombinant lacritin on human cells. Higher human lacritin concentrations are optimal on rat or mouse cells or on rabbit eyes. A biphasic dose response has a bell-shaped curve, with doses lower or higher than the dose optimum less effective. Other mitogens share this property. However, in secretion assays using monkey lacritin on monkey lacrimal acinar cells, the dose response appears to be sigmoidal with increasing lipocalin or lactoferrin secretion through a 0.1, 0.3 and 1 µM dose range. Lacritin flows downstream from the lacrimal gland through ducts onto the eye. Artificial depletion of lacritin from normal human tears revealed that tears lacking lacritin are unable to promote the survival of ocular surface cells stressed with inflammatory cytokines. Human dry eye tears also lack this activity. However, dry eye tears supplemented with lacritin are fully protective. Similarly, tears artificially depleted of lacritin are deficient in bactericidal activity. These observations suggest that among all tear proteins, lacritin may be the master protector. # Signaling Lacritin mitogenic, survival and secretion signaling have been studied. Lacritin mitogenic signaling follows two pathways: - Gαi or Gαo → PKCα/PLCγ2 → Ca2+ → calcineurin → NFATC1 - Gαi or Gαo → PKCα/PLCγ2/PLD1 → mTOR Rapid dephosphorylation of PKCα causes it to transiently move from the cytoplasm to the area of the Golgi apparatus and peripheral nucleus. Here, it forms a complex with PKCα and PLCγ2 from which downstream mTOR and NFAT signaling is initiated. The upstream Gαi or Gαo signaling suggests the involvement of a G-protein-coupled receptor (GPCR). A candidate GPCR is under study. Syndecan-1 likely serves as a co-receptor. Binding lacritin may improve its GPCR affinity. Lacritin survival signaling is observed when cells are stressed. Lacritin promotes survival and homeostasis by transiently stimulating autophagy. The mechanism appears to involve lacritin stimulated acetylation of the transcription factor FOXO3. Acetylated FOXO3 serves as a ligand for the autophagic mediator ATG101. Lacritin also promotes coupling of FOXO1 (that becomes acetylated with stress) with autophagic mediator ATG7. In the absence of lacritin, no coupling is observed. Thus acetylation alone is likely insufficient for FOXO1-ATG7 ligation, unlike an initial claim. Lacritin also restores oxidative phosphorylation and other metabolic events to rescue cells from stress. Lacritin stimulated secretion of tear proteins lipocalin and lactoferrin from monkey lacrimal acinar cells does not appear to be mediated by Ca2+, unlike the agonist carbachol. When monkey lacrimal acinar cells are stressed with inflammatory cytokines (as occurs in dry eye), carbachol loses its capacity to promote the secretion of lipocalin. However, lacritin stimulates lipocalin secretion even in the presence of stress. # Distribution ## Species Genomic sequencing assembled by Ensembl reveals the existence of putative lacritin orthologues in other species. Comparative genomic alignment suggests that horse lacritin is most similar to human lacritin among all non-primate sequences examined. Moreover, it is detectable in horse tears by immunoblotting or by ELISA. Antibodies directed to the C-, but not N-, terminus of human lacritin are most effective - in keeping with the predicted conservation of the C-terminal amphipathic alpha helix necessary for cell targeting. ## Tissue Tissue distribution has been examined in humans and monkeys. Lacritin is most highly expressed in the lacrimal gland, including the accessory lacrimal gland of Wolfring. Expression is moderate in salivary glands and slight in mammary (cancer but not or rarely normal), and thyroid glands. The salivary gland expression appears to be attributable to a discrete group of unidentified ductal-like cells. Some lacritin was reported in lung bronchoalveolar lavage and plasma. In lacrimal gland, polarized lacrimal acinar cells appear to be the most prolific lacritin producers, as evidenced by strong staining of secretory granules in keeping with lacritin release after carbachol stimulation. Carbachol-dependent release involves PKC and calcium signaling. Some lacritin is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea that together with lacrimal gland comprise much of the lacrimal functional unit (LFU). Viewed collectively, the LFU is the primary source of lacritin in the body, and the eye the main target. # Disease Dry eye is the most common eye disease, affecting 5 - 6% of the population. Prevalence rises to 6 - 9.8% in postmenopausal women, and as high as 34% in the elderly. Tears lubricate the lid and are important for the refraction of light. Tears also promote epithelial health. Only a small fraction of the estimated 1543 proteins in tears are differentially deficient or upregulated in dry eye. Lacritin monomer is differentially downregulated in mild to severe aqueous deficient dry eye, and in contact lens-related dry eye. In a larger trial, 95% of tears from patients with aqueous deficient dry eye were lacritin monomer deficient. Two studies that did not differentiate monomer from multimer did note any change of lacritin in dry eye. Topical treatment of eyes of dry eye mice (Aire knockout mouse model of dry eye) restored tearing, and suppressed both corneal staining and the size of inflammatory foci in lacrimal glands. Lacritin monomer deficiency in tears of patients with blepharitis was also reported. Blepharitis is an inflammation of the eyelid often associated with dry eye. In climatic droplet keratopathy, N119 appears to be un-glycosylated. Also a normal breast cancer localization reported by some has not been replicated in Unigene (the 'mammary gland' hit is for breast cancer) and gene array studies, but some breast cancers appear to display elevated expression or LACRT gene amplification. iTRAQ analysis of tears from diabetics at different stages of disease detected relatively more lacritin, lysozyme, lipophilin A, lipocalin 1, immunoglobulin lambda chain and lactotransferrin in tears of patients with diabetic retinopathy. The analysis did not distinguish lacritin monomer from polymer, and proposed the application of all as biomarkers. Tear lacritin monomer is barely detectable in the initial stage of infection by Fusarium solani in fungal keratitis. Also down regulated are tear lipocalin-1 and cystatin S. Fungal keratitis accounts for half of all corneal ulcers in Africa and India - the primary source of blindness in these countries.	Lacritin Lacritin is a 12.3 kDa glycoprotein encoded in humans by the LACRT gene.[1][2] Lacritin's discovery emerged from a screen for factors that stimulate tear protein secretion.[2][3] Lacritin is a secreted protein found in tears and saliva. Lacritin also promotes tear secretion,[2][4] the proliferation[2] and survival of epithelial cells,[5] and corneal wound healing[6] Lacritin is thus a multifunctional prosecretory mitogen with cell survival activity. Natural or bacterial cleavage of lacritin releases a C-terminal fragment that is bactericidal.[7] Most lacritin is produced by the lacrimal gland,[2] including the accessory lacrimal gland of Wolfring.[8] Some lacritin is produced by the meibomian gland, and by epithelial cells of the conjunctiva and cornea.[9] Together these epithelia comprise much of the lacrimal functional unit (LFU). Dry eye is the most common disease of the LFU. A growing number of studies suggest that lacritin may be differentially downregulated in dry eye,[10] including contact lens-related dry eye.[11] Topical lacritin promotes tearing in rabbit preclinical studies.[12] In the Aire knockout mouse model of dry eye (considered similar to human Sjogren's syndrome), topical lacritin restores pilocarpine-induced tearing, largely eliminates lissamine green staining and reduces the size of inflammatory foci in the lacrimal gland.[13] Lacritin cell targeting is dependent on the cell surface heparan sulfate proteoglycan syndecan-1 (SDC1).[14][15] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[14] A G-protein-coupled receptor (GPCR) then appears to be ligated.[16] Targeted cells signal to NFAT and mTOR[16] if conditions are suitable for proliferation, or to AKT and FOXO3 under conditions of stress.[5] # Structure Lacritin consists of 119 amino acids after cleavage of the N-terminal signal peptide and displays several predicted alpha helices, mostly in the C-terminal half. Of these, the two C-terminal ones have been confirmed by circular dichroism.[16] The most C-terminal alpha helix is amphipathic with hydrophobic and hydrophilic residues on opposite faces. The hydrophobic face is an important syndecan-1 binding element.[15] PONDR (Predictor of Naturally Disordered Regions)[17] predicts that the C-terminal and N-terminal halves are respectively 'ordered' and 'disordered'. 11 - 12 predicted O-glycosylation sites populate the N-terminal half. The C-terminal amphipathic alpha helix is also the site of lacritin's only N-glycosylation site. In 'climatic droplet keratopathy' this site is not glycosylated.[18] Lacritin recombinantly generated in E. coli (no glycosylation) and lacritin in tears (glycosylated) differ in size with respective mobilities of ~18 and ~25 kDa by SDS-PAGE. With a predicted protein core molecular weight of 12.3 kDa, it is possible that mobility is partially retarded by lacritin's amphipathic alpha helices. Predicted pI of lacritin's core protein is 5.[10] Lacritin is subject to crosslinking by tissue transglutaminase, thereby giving rise to lacritin multimers including dimers and trimers.[19] Crosslinking is initiated within 1 min in vitro, requiring as little as 0.1 nM lacritin.[19] The ~0.6 micro molar level of tissue transglutaminase estimated in human tears is sufficient to promote crosslinking.[19] Crosslinking involves the donors lysine 82 and 85 and the acceptor glutamine 106.[19] Glutamine 106 resides within the amphipathic alpha helix near the C-terminus responsible for binding the N-terminus of syndecan-1.[15] Accordingly, crosslinked lacritin binds syndecan-1 poorly[19] and is inactive. Several lacritin splice variants have been detected in Aceview,[20] from NEIBank EST data.[21] Lacritin-b (11.1 kDa; pI 5.3) lacks the sequence SIVEKSILTE. Lacritin-c (10.7 kDa; pI 4.6) displays a novel C-terminus that should be incapable of binding syndecan-1, and lacks cell survival activity.[5] # Cell targeting Lacritin targets a restricted group of epithelial cells (including human corneal epithelia), and not fibroblastic, glioma, or lymphoblastic cells.[16] Cell surface proteoglycan syndecan-1 is partly responsible.[14][15] Biotinylated cell surface proteins from a lacritin-responsive cell were incubated with lacritin under conditions of physiological salt. Those that bound lacritin were sequenced by mass spectrometry. Few bound. The most prominent was syndecan-1 (SDC1). In confirmatory pull-down assays, binding was not shared with family members syndecan-2 or syndecan-4,[14] indicating that the protein core (and not the negatively charged heparan sulfate side-chains) was the main site of binding. Further analysis narrowed the site to syndecan-1's N-terminal 51 amino acids,[14] and subsequently to the N-terminal sequence GAGAL that is conserved in syndecan-1's from different species.[15] GAGAL promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix and likely binds to the hydrophobic face.[15] Syndecan-1 binds many growth factors through its long heparan sulfate side-chains. Yet, long heparan sulfate chains interfere with lacritin binding. Since syndecans are always decorated with heparan sulfate, this means that heparanase must be available to partially or completely cleave off heparan sulfate, allowing lacritin to bind. Indeed, no binding was detected from cells lacking heparanase after siRNA depletion.[14] Binding was restored by spiking in exogenous heparanase or heparitinase.[14] Thus, heparanase regulates lacritin function as an 'on-switch'. Exposed 3-O sulfated group(s) on heparanase-cleaved heparan sulfate[15] (that likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix), and an N-terminal chondroitin sulfate chain (likely also binds to the cationic face) appear to contribute to binding.[15] Point mutagenesis of lacritin has narrowed the ligation site.[15] This novel heparanase mechanism appears at first glance to be poor for ocular health since heparanase release from invading lymphocytes in the corneal stroma is inflammatory. Yet heparanase is a normal secretory product of the corneal epithelium.[22] Lacritin-dependent mitogenesis is inhibitable by pertussis toxin,.[16] The implication is that another key element of lacritin targeting specificity is a G-protein-coupled receptor that would presumably form a cell surface targeting complex with SDC1. Involvement of a G-protein coupled receptor would explain the rapidity of lacritin signaling. # Function Lacritin is a glycoprotein of the human tear film, and to a lesser extent of saliva, lung lavage[23] and plasma.[24] It is mainly produced by the lacrimal gland.[2] Some lacritin also is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea.[9] The lacritin gene (LACRT) is one of the most transcriptionally regulated genes in the human eye.[25] Functional studies suggest a role in epithelial renewal of some non-germative epithelia. By flowing downstream through ducts, it may generate a 'proliferative field'.[16] Lacritin also promotes secretion[2] (including that of lipocalin-1 and lactoferrin[4]), cell survival and regeneration of the corneal epithelium after wounding.[6] This raises the possibility that lacritin may have clinical applications in the treatment of dry eye, the most common eye disease. It also may be beneficial in promoting healing after LASIK or PRK surgery. Recent studies suggest that lacritin monomer is differentially down regulated in not only in dry eye,[26] but also in blepharitis.[27] Lacritin is an LFU prosecretory mitogen and survival factor with a biphasic dose response that is optimal at 1 - 10 nM for human recombinant lacritin on human cells.[16] Higher human lacritin concentrations are optimal on rat or mouse cells[2] or on rabbit eyes.[12] A biphasic dose response has a bell-shaped curve, with doses lower or higher than the dose optimum less effective. Other mitogens share this property.[16] However, in secretion assays using monkey lacritin on monkey lacrimal acinar cells, the dose response appears to be sigmoidal with increasing lipocalin or lactoferrin secretion through a 0.1, 0.3 and 1 µM dose range.[4] Lacritin flows downstream from the lacrimal gland through ducts onto the eye. Artificial depletion of lacritin from normal human tears revealed that tears lacking lacritin are unable to promote the survival of ocular surface cells stressed with inflammatory cytokines.[5] Human dry eye tears also lack this activity. However, dry eye tears supplemented with lacritin are fully protective.[5] Similarly, tears artificially depleted of lacritin are deficient in bactericidal activity.[7] These observations suggest that among all tear proteins, lacritin may be the master protector. # Signaling Lacritin mitogenic, survival and secretion signaling have been studied. Lacritin mitogenic signaling[16] follows two pathways: - Gαi or Gαo → PKCα/PLCγ2 → Ca2+ → calcineurin → NFATC1 - Gαi or Gαo → PKCα/PLCγ2/PLD1 → mTOR Rapid dephosphorylation of PKCα causes it to transiently move from the cytoplasm to the area of the Golgi apparatus and peripheral nucleus. Here, it forms a complex with PKCα and PLCγ2 from which downstream mTOR and NFAT signaling is initiated.[16] The upstream Gαi or Gαo signaling suggests the involvement of a G-protein-coupled receptor (GPCR). A candidate GPCR is under study. Syndecan-1 likely serves as a co-receptor. Binding lacritin may improve its GPCR affinity. Lacritin survival signaling is observed when cells are stressed.[5] Lacritin promotes survival and homeostasis by transiently stimulating autophagy.[5] The mechanism appears to involve lacritin stimulated acetylation of the transcription factor FOXO3. Acetylated FOXO3 serves as a ligand for the autophagic mediator ATG101. Lacritin also promotes coupling of FOXO1 (that becomes acetylated with stress) with autophagic mediator ATG7. In the absence of lacritin, no coupling is observed.[5] Thus acetylation alone is likely insufficient for FOXO1-ATG7 ligation, unlike an initial claim.[28] Lacritin also restores oxidative phosphorylation and other metabolic events to rescue cells from stress.[5] Lacritin stimulated secretion of tear proteins lipocalin and lactoferrin from monkey lacrimal acinar cells does not appear to be mediated by Ca2+, unlike the agonist carbachol.[4] When monkey lacrimal acinar cells are stressed with inflammatory cytokines (as occurs in dry eye), carbachol loses its capacity to promote the secretion of lipocalin. However, lacritin stimulates lipocalin secretion even in the presence of stress.[4] # Distribution ## Species Genomic sequencing assembled by Ensembl reveals the existence of putative lacritin orthologues in other species.[29] Comparative genomic alignment suggests that horse lacritin is most similar to human lacritin among all non-primate sequences examined.[26] Moreover, it is detectable in horse tears by immunoblotting or by ELISA.[30] Antibodies directed to the C-, but not N-, terminus of human lacritin are most effective[30] - in keeping with the predicted conservation of the C-terminal amphipathic alpha helix[30] necessary for cell targeting.[14] ## Tissue Tissue distribution has been examined in humans and monkeys. Lacritin is most highly expressed in the lacrimal gland, including the accessory lacrimal gland of Wolfring.[8] Expression is moderate in salivary glands and slight in mammary (cancer but not or rarely normal), and thyroid glands.[2][25][31][32] The salivary gland expression appears to be attributable to a discrete group of unidentified ductal-like cells.[2] Some lacritin was reported in lung bronchoalveolar lavage[33] and plasma.[24] In lacrimal gland, polarized lacrimal acinar cells appear to be the most prolific lacritin producers, as evidenced by strong staining of secretory granules[2] in keeping with lacritin release after carbachol stimulation.[9] Carbachol-dependent release involves PKC and calcium signaling.[34] Some lacritin is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea [9] that together with lacrimal gland comprise much of the lacrimal functional unit (LFU). Viewed collectively, the LFU is the primary source of lacritin in the body, and the eye the main target.[2] # Disease Dry eye is the most common eye disease, affecting 5 - 6% of the population. Prevalence rises to 6 - 9.8% in postmenopausal women,[35] and as high as 34% in the elderly.[36] Tears lubricate the lid and are important for the refraction of light. Tears also promote epithelial health. Only a small fraction of the estimated 1543 proteins[37] in tears are differentially deficient or upregulated in dry eye.[26] Lacritin monomer is differentially downregulated in mild to severe aqueous deficient dry eye,[38] and in contact lens-related dry eye.[11] In a larger trial, 95% of tears from patients with aqueous deficient dry eye were lacritin monomer deficient.[39] Two studies that did not differentiate monomer from multimer did note any change of lacritin in dry eye. Topical treatment of eyes of dry eye mice (Aire knockout mouse model of dry eye) restored tearing, and suppressed both corneal staining and the size of inflammatory foci in lacrimal glands.[13] Lacritin monomer deficiency in tears of patients with blepharitis was also reported.[27] Blepharitis is an inflammation of the eyelid often associated with dry eye.[10] In climatic droplet keratopathy, N119 appears to be un-glycosylated. Also a normal breast cancer localization reported by some has not been replicated in Unigene (the 'mammary gland' hit is for breast cancer) and gene array studies,[32] but some breast cancers appear to display elevated expression[32] or LACRT gene amplification.[40] iTRAQ analysis of tears from diabetics at different stages of disease detected relatively more lacritin, lysozyme, lipophilin A, lipocalin 1, immunoglobulin lambda chain and lactotransferrin in tears of patients with diabetic retinopathy. The analysis did not distinguish lacritin monomer from polymer, and proposed the application of all as biomarkers.[41] Tear lacritin monomer is barely detectable in the initial stage of infection by Fusarium solani in fungal keratitis.[42] Also down regulated are tear lipocalin-1 and cystatin S.[42] Fungal keratitis accounts for half of all corneal ulcers in Africa and India[43][44][45] - the primary source of blindness in these countries.[46]	https://www.wikidoc.org/index.php/Lacritin
35be9ce3a6e70ea46e9ee2680bcbdccae2c9e058	wikidoc	Lactitol	Lactitol # Overview Lactitol is a sugar alcohol used as a replacement bulk sweetener for low calorie foods with approximately 40% of the sweetness of sugar. It is also used medically as a laxative. Lactitol is produced by two manufacturers, Danisco and Purac Biochem. # Applications Lactitol is used in a variety of low food energy or low fat foods. High stability makes it popular for baking. It is used in sugar-free candies, cookies (biscuits), chocolate, and ice cream. Lactitol also promotes colon health as a prebiotic. Because of poor absorption, lactitol only has 2.4 Calories (9 kilojoules) per gram, compared to 4 Calories (17 kJ) per gram for typical carbohydrates. Lactitol is listed as an excipient in some prescription drugs, such as Adderall. Lactitol is a laxative and is used to prevent or treat constipation, e.g. under the trade name Importal. Lactitol in combination with Ispaghula husk is an approved combination for idiopathic constipation as a laxative and is used to prevent or treat constipation. # Safety and health Lactitol, erythritol, sorbitol, xylitol, mannitol, and maltitol are all sugar alcohols. The United States Food and Drug Administration (FDA) classifies sugar alcohols as "generally recognized as safe" (GRAS). They are approved as food additives, and are recognized as not contributing to tooth decay or causing increases in blood glucose. Lactitol is also approved for use in foods in most countries around the world. Like most other sugar alcohols (with the exception of erythritol), lactitol can cause cramping, flatulence, and diarrhea in some individuals. This is because humans lack a suitable beta-galactosidase in the upper gastrointestinal (GI) tract, and a majority of ingested lactitol reaches the large intestine, where it then becomes fermentable to gut microbes (prebiotic) and can pull water into the gut by osmosis. In a human study with sweetened chocolate, consumption of 5 g per day or less resulted in no GI changes, and 10 g per day caused few changes. Those with other health conditions should consult their GP or dietician prior to consumption.	Lactitol Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Lactitol is a sugar alcohol used as a replacement bulk sweetener for low calorie foods with approximately 40% of the sweetness of sugar. It is also used medically as a laxative. Lactitol is produced by two manufacturers, Danisco and Purac Biochem. # Applications Lactitol is used in a variety of low food energy or low fat foods. High stability makes it popular for baking. It is used in sugar-free candies, cookies (biscuits), chocolate, and ice cream. Lactitol also promotes colon health as a prebiotic. Because of poor absorption, lactitol only has 2.4 Calories (9 kilojoules) per gram, compared to 4 Calories (17 kJ) per gram for typical carbohydrates. Lactitol is listed as an excipient in some prescription drugs, such as Adderall.[1] Lactitol is a laxative and is used to prevent or treat constipation, e.g. under the trade name Importal.[2] Lactitol in combination with Ispaghula husk is an approved combination for idiopathic constipation as a laxative and is used to prevent or treat constipation. # Safety and health Lactitol, erythritol, sorbitol, xylitol, mannitol, and maltitol are all sugar alcohols. The United States Food and Drug Administration (FDA) classifies sugar alcohols as "generally recognized as safe" (GRAS). They are approved as food additives, and are recognized as not contributing to tooth decay or causing increases in blood glucose. Lactitol is also approved for use in foods in most countries around the world. Like most other sugar alcohols (with the exception of erythritol), lactitol can cause cramping, flatulence, and diarrhea in some individuals. This is because humans lack a suitable beta-galactosidase in the upper gastrointestinal (GI) tract, and a majority of ingested lactitol reaches the large intestine,[3] where it then becomes fermentable to gut microbes (prebiotic) and can pull water into the gut by osmosis. In a human study with sweetened chocolate, consumption of 5 g per day or less resulted in no GI changes, and 10 g per day caused few changes.[4] Those with other health conditions should consult their GP or dietician prior to consumption.	https://www.wikidoc.org/index.php/Lactitol
94a41e0e9b8586f6d39177e0db77a81192ac2427	wikidoc	Lamiales	Lamiales The order Lamiales is a taxon in the asterid group of dicotyledonous flowering plants. It includes approximately 11,000 species divided up into about 10 families. Well-known members of this order include the lavender, the lilac, the olive, the jasmine, the ash tree, the teak, the snapdragon, and a number of table herbs such as mint, basil, and rosemary. # Characteristics Species in this order typically have the following characteristics, although there are exceptions to all of them: - superior ovary composed of two fused carpels - five petals fused into a tube - bilaterally symmetrical, often bilabiate corollas - four (or fewer) fertile stamens # Taxonomic history Lamiales formerly had a restricted circumscription (e.g., by Arthur Cronquist) that included the major families Lamiaceae (Labiatae), Verbenaceae, and Boraginaceae plus a few smaller families. Recent phylogenetic work has shown that Lamiales is polyphyletic with respect to order Scrophulariales and the two groups are now usually combined in a single order that also includes the former orders Hippuridales and Plantaginales. Lamiales has become the preferred name for this much larger combined group. The placement of Boraginaceae is unclear but phylogenetic work shows that this family does not belong in Lamiales. Also, the circumscription of family Scrophulariaceae, formerly a paraphyletic group defined primarily by plesiomorphic characters and from within which numerous other families of the Lamiales were derived, has been radically altered to create a number of smaller, better-defined and putatively monophyletic families.	Lamiales The order Lamiales is a taxon in the asterid group of dicotyledonous flowering plants. It includes approximately 11,000 species divided up into about 10 families. Well-known members of this order include the lavender, the lilac, the olive, the jasmine, the ash tree, the teak, the snapdragon, and a number of table herbs such as mint, basil, and rosemary. # Characteristics Species in this order typically have the following characteristics, although there are exceptions to all of them: - superior ovary composed of two fused carpels - five petals fused into a tube - bilaterally symmetrical, often bilabiate corollas - four (or fewer) fertile stamens # Taxonomic history Lamiales formerly had a restricted circumscription (e.g., by Arthur Cronquist) that included the major families Lamiaceae (Labiatae), Verbenaceae, and Boraginaceae plus a few smaller families. Recent phylogenetic work has shown that Lamiales is polyphyletic with respect to order Scrophulariales and the two groups are now usually combined in a single order that also includes the former orders Hippuridales and Plantaginales. Lamiales has become the preferred name for this much larger combined group. The placement of Boraginaceae is unclear but phylogenetic work shows that this family does not belong in Lamiales. Also, the circumscription of family Scrophulariaceae, formerly a paraphyletic group defined primarily by plesiomorphic characters and from within which numerous other families of the Lamiales were derived, has been radically altered to create a number of smaller, better-defined and putatively monophyletic families. # External links Template:Wikispecies - Lamiales - A parsimony analysis of the Asteridae sensu lato based on rbcL sequences - Distintegration of the Scrophulariaceae (deals with relationships throughout Lamiales) - http://www.itis.usda.gov of 2002-05-31 TSN: 500018 - L. Watson and M.J. Dallwitz (1992 onwards). The families of flowering plants: descriptions, illustrations, identification, information retrieval. http://delta-intkey.com - http://www.biologie.uni-hamburg.de/b-online/vascular/acanth.htm 2002-09-06 - http://www.biologie.uni-hamburg.de/b-online/d52/52e.htm 2002-09-06 - http://www.biologie.uni-hamburg.de/b-online/d52/52efam.htm 2002-09-06 - http://www.science.siu.edu/parasitic-plants/Relation-Scroph.html - http://www.rbgkew.org.uk/web.dbs/genlist.html 2002-09-06 ca:Lamial da:Læbeblomst-ordenen de:Lippenblütlerartige et:Iminõgeselaadsed ko:꿀풀목 he:צינוראים it:Lamiales lt:Notreliečiai hu:Árvacsalán-virágúak ms:Lamiales nl:Lamiales no:Lamiales fi:Lamiales sv:Lamiales uk:Губоцвіті sr:Lamiales Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Lamiales
76d131ad9ebb1216546df001024d3114a2dca8c6	wikidoc	Lamin B2	Lamin B2 Lamin B2 is a protein that in humans is encoded by the LMNB2 gene. It is the second of two type B nuclear lamins, and it is associated with laminopathies. # Model organisms Model organisms have been used in the study of Lamin B2 function. A conditional knockout mouse line, called Lmnb2tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and four significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Male heterozygotes displayed increased circulating creatinine levels and an increased susceptibility to Salmonella infection.	Lamin B2 Lamin B2 is a protein that in humans is encoded by the LMNB2 gene. It is the second of two type B nuclear lamins, and it is associated with laminopathies. # Model organisms Model organisms have been used in the study of Lamin B2 function. A conditional knockout mouse line, called Lmnb2tm1a(KOMP)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[8][9][10] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty four tests were carried out on mutant mice and four significant abnormalities were observed.[4] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Male heterozygotes displayed increased circulating creatinine levels and an increased susceptibility to Salmonella infection.[4]	https://www.wikidoc.org/index.php/Lamin_B2
c20e84776204de08ac6cceeb73bf7c3a3f87a2ac	wikidoc	Langerin	Langerin CD207, langerin (Cluster of Differentiation 207) is a protein which in humans is encoded by the CD207 gene. Langerin is a type II transmembrane, C-type lectin receptor on Langerhans cells. # Function The protein encoded by this gene is expressed in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. Additionally it is known by the name C-type lectin domain family 4 member K (CD antigen CD207). It is also expressed in several other dendritic cell types including dermal CD103+ DCs and splenic CD8+ DCs. Langerin is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway. # Clinical significance Langerin on mucosal Langerhans cells of the human genital epithelium binds to HIV-1 and subsequently internalizes it into Birbeck granules to be degraded.	Langerin CD207, langerin (Cluster of Differentiation 207) is a protein which in humans is encoded by the CD207 gene.[1][2] Langerin is a type II transmembrane, C-type lectin receptor on Langerhans cells.[2][3] # Function The protein encoded by this gene is expressed in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. Additionally it is known by the name C-type lectin domain family 4 member K (CD antigen CD207). It is also expressed in several other dendritic cell types including dermal CD103+ DCs and splenic CD8+ DCs. Langerin is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway.[1] # Clinical significance Langerin on mucosal Langerhans cells of the human genital epithelium binds to HIV-1 and subsequently internalizes it into Birbeck granules to be degraded.[4][5]	https://www.wikidoc.org/index.php/Langerin
61037d67826256e9d68d45aed9620e525a5be65e	wikidoc	Laudanum	Laudanum Laudanum is an opium tincture, sometimes sweetened with sugar and also called wine of opium. # History In the 16th century, Paracelsus experimented with the medical value of opium. He decided that its medical (analgesic) value was of such magnitude that he called it Laudanum, from the Latin laudare, to praise, or from labdanum, the term for a plant extract. He did not know of its addictive properties. In the 19th century, laudanum was used in many patent medicines to "relieve pain... to produce sleep... to allay irritation... to check excessive secretions... to support the system... as a sudorific". The limited pharmacopoeia of the day meant that opium derivatives were among the most efficacious of available treatments, and so laudanum was widely prescribed for ailments from colds to meningitis to cardiac diseases, in both adults and children. Laudanum was used during the yellow fever epidemic. The Romantic and Victorian eras were marked by the widespread use of laudanum in Europe and the United States. Initially a working class drug, laudanum was cheaper than a bottle of gin or wine, because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage. Literary figures of note who used laudanum include: - Lord Byron - Jane Johnston Schoolcraft, the early American Indian writer - Kate Chopin - Samuel Taylor Coleridge, who was addicted for much of his adult life - Thomas de Quincey, who turned his addiction into literary success with the publication of Confessions of an English Opium Eater - Percy Bysshe Shelley, who suffered raging laudanum-induced hallucinations - John Keats - Lewis Carroll of which some inspiration of Alice in Wonderland could have come from - Iolo Morgannwg, the Welsh antiquarian - Charles Dickens - Antonin Artaud - Edgar Allan Poe - Charles Baudelaire - Branwell Brontë (brother of the Brontë sisters). - Mary Todd Lincoln, wife of President Abraham Lincoln, misprescribed for sleep problems, which caused anxiety and hallucinations. Upon increase of these hallucinations, more laudanum and chloral hydrate was administered, which increased the problem and led to her eventual commitment to an asylum. Political figures who used the drug included George Washington, William Wilberforce and Meriwether Lewis. Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches and used it to achieve the pallid complexion associated with tuberculosis (frailty and paleness were particularly prized in females at the time). Nurses also spoon-fed laudanum to infants. The Pre-Raphaelite muse Elizabeth Siddal died of a laudanum overdose. # Depictions in fiction ## Literature - In William Faulkner's novel "Pylon", the reporter tries to buy absinthe, but is given gin with laudanum in it. - In Thomas Harris's novel Hannibal Rising, Hannibal Lecter is asked by a condemned prisoner to give him laudanum before facing death by guillotine, in exchange for allowing his body to be used in a Paris medical school. It is later suggested that this was common practice at the time. - In Patrick O'Brian's Aubrey–Maturin series of novels, the ship's surgeon, Stephen Maturin, both uses the drug professionally and battles his own addiction to it. - In Alan Moore's The League of Extraordinary Gentlemen, Allan Quatermain, opium-addicted, uses his bottle of laudanum to paralyze Edward Hyde. - In Joanne Harris's 1993 novel Sleep Pale Sister, Effie was fed laudanum to keep her out of "hysterics" and also so that she could sleep. - The character of Oscar Hopkins in Peter Carey's novel Oscar and Lucinda (1988) uses laudanum, initially under duress, to dull his hydrophobia during his expedition from Sydney. - Mary Shelley's character Victor Frankenstein uses laudanum to help him sleep after the death of his friend, Henry Clerval. - In E.L. Doctorow's Ragtime, Harry K. Thaw is said to have once drank an entire bottle of laudanum. - In Jack Finney's Time and Again, the main character, Si Morley, wonders if a live baby in an 1882 display case has been "doped up with one of the laudanum preparations I'd seen advertised in Harpers." - Laudanum is also used as a means to circumvent Speck magic in the Soldier Son Trilogy by Robin Hobb. - Laudanum is mentioned frequently in William S. Burroughs' Naked Lunch, and The Nova Trilogy, beginning with The Soft Machine. - In the tenth chapter of James Joyce's Ulysses, Haines is depicted drinking laudanum from a phial. - In Octavia E. Butler's Kindred, Rufus' mother uses laudanum as a medicine to relieve her pain. - In Wilkie Collins' The Moonstone (1868), a valuable diamond, the Moonstone, is stolen by a character in a laudanum-induced stupor. - It is mentioned in Sarah Waters' Tipping the Velvet as a way a nanny calmed the child Cyril, and thus an argument for Nancy to stay with that family and watch the child during the day. - The character Cassy in Uncle Tom's Cabin kills one of her children with laudanum to prevent it from growing up in slavery. - Hannibal Sefton, a tuberculosis-afflicted violinist in Barbara Hambly's Benjamin January mystery series, is addicted to laudanum, and uses it as a means of self-medication. - It appears in the hard-boiled detective novels of Dashiell Hammett and Raymond Chandler, including Red Harvest and The Big Sleep, respectively. - In Charles Dickens' novel The Mystery of Edwin Drood it is the drink of choice for the sinister uncle Jasper. - In Love in the Time of Cholera by Gabriel Garcia Marquez, laudanum is the drink that America Vicuna uses to kill herself. - In One Hundred Years of Solitude by Gabriel Garcia Marquez, Amaranta decides to poison her adopted sister Rebeca with laudanum in order to prevent the latter's marriage to Pietro Crespi, whom Amaranta secretly loves. Instead, Amaranta inadvertently poisons her innocent sister-in-law Remedios Mascote. - In "Kal" by Judy Nunn, the character "Carmelina" is given laudanum by Lewis as a sexual enhancement; (p568)"Just a sip, my darling, just for fun", He'd said the first time he offered her the spoon.....and of course, she'd obeyed. - In Affinity (novel) by Sarah Waters, protagonist Margaret Prior takes laudanum as advised by her doctor. - In Cloud Atlas, one of the protagonists Adam Ewing is made to become addicted to laudanum after being fed it as medicine by another passenger without being aware of its nature. - In Bram Stoker's Dracula Lucy Westenra's maids are poisoned (though not killed) by Dracula with a dose of laudanum put into wine. - In Interview with the Vampire (from The Vampire Chronicles series by Anne Rice), Claudia gives a deadly dose of laudanum to two orphans whom Lestat is tricked into feeding upon, thus poisoning him. - In The House of the Scorpion by Nancy Farmer, the protagonist, Matt is accused of killing the dog of his friend, Maria, by adding laudanum to its meat. - In Alice Munro's short story "Meneseteung", Almeda Roth, an eccentric spinster, is imagined (by the narrator) to have taken laudanum ("Many ladies did", Munro writes.) - In Libba Bray's novels A Great and Terrible Beauty ,Rebel Angels and The Sweet Far Thing, Gemma's father is addicted to laudanum as a result of the death of his wife. - Samuel Taylor Coleridge wrote the poem fragment Kubla Khan immediately on waking from a laudanum-induced dream. - In Robery Hicks novel The Widow of the South laudanum is mentioned by Carrie McGavock as a method of controlling grief in women whose husbands and sons had gone to war. - Also in the novel Freaks: Alive, on the Inside, author Annette Curtis Klause has a character by the name of Ceecee harboring a dangerous secret of laudanum addiction. - Dirk Gently's Holistic Detective Agency by Douglas Adams references Samuel Taylor Coleridge's use of Laudanum. - In Asterix, Laudanum is one of the four Roman encampments surrounding the protagonists' village. - In the Great and Terrible Beauty novels by Libba Bray, the protagonist, Gemma, is the daughter of a laundanum addict. Her father takes up the drug after the death of his wife (her mother) Virginia. ## Film - In the 2001 movie From Hell laudanum plays an important role: Jack the Ripper is shown using it to numb his victims, while Inspector Frederick Abberline (played by Johnny Depp) uses a laudanum and absinthe mixture to see visions of the future or past. - In John Wayne's final movie The Shootist, his character J.B. Books is suffering from terminal cancer, and his doctor E.W. Hostetler (played by James Stewart) prescribes laudanum to relieve the pain. - In Amazing Grace, the William Wilberforce Story, there are numerous scenes of Wilberforce being given laudanum to relieve symptoms of colitis. - In Cold Mountain the main character Inman gets a drink with laudanum from the old woman who killed her goat to feed him. - In Master and Commander: The Far Side of the World, the doctor issues laudanum to a boy whose arm is to be amputated. - In the 1971 movie The Beguiled, Geraldine Page's character used laudanum to sedate Clint Eastwood's character when she amputated his leg. - In Shadow of the Vampire F.W. Murnau (played by John Malkovich) is discovered using laudanum by his cinematographer. - In Tombstone, Mattie Blaylock, Wyatt Earp's common law wife, is depicted as a laudanum addict, true to her real-life addiction. - In the 1995 Ang Lee adaptation of Jane Austen's Sense and Sensibility, Doctor Harris (Oliver Ford Davies) gives Laudanum to a heartbroken Marianne Dashwood (Kate Winslet) to bring down an infectious fever after she ventures out in a storm to see Willoughby's Estate. - In the movie House of Mirth, Gillian Anderson's character Lily Bart uses laudanum to escape her troubles. - In the film Interview with the Vampire: The Vampire Chronicles, Claudia poisons two young boys with laudanum to keep their blood warm and fool Lestat into drinking from them. ## Television - Alma Garrett (played by Molly Parker) was addicted to laudanum in Deadwood. - In the Hornblower television movies "The Mutiny" and "Retribution", Dr. Clive (played by David Rintoul) freely dispensed laudanum to injured or beaten seamen, to the mentally unstable Captain Sawyer (played by David Warner), and to himself. - In an episode of the Little House on the Prairie television series titled "Blizzard", several children are experiencing pain in their hands and feet as they are warmed up in the schoolhouse after suffering from partial hypothermia and frostbite. To help them with the pain, Dr. Baker issues laudanum, but "just half a teaspoon!". - In the first episode of the 19th season of The Simpsons, entitled "He Loves To Fly And He D'oh's", Mr. Burns has a shopping list on which "Laudanum" is first on the list. Followed by: "cotton gin", "spats", "cell phone" and "Brooklyn Dodgers." - In episode seven of the first season of Bramwell, Lady Cora Peters (played by actress Michele Dotrice) suffered acute stomach pains which turned out to be appendicitis inaccurately diagnosed as tifilitis by her doctor who prescribed a small bottle of laudanum to ease her pain. ## Music - laudanum is the french electronic project of Matthieu Malon who releases several singles & also 2 albums with that name : system:on in 2002 & your place & time will be mine in 2006. his myspace page & his label. - Avec Laudenum is the title of the fifth release by the ambient group Stars of the Lid. - "Laudanum" is the title of the fifth track on the CD Wholesale Meats and Fish by Letters to Cleo. - Laudanum is mentioned in the song "The Legionnaire's Lament" by The Decemberists. - Laudanum is the name of a song by Montreal Guitar Prodigy Domininc Cifarelli's "The Chronicles of Israfel" - Laudanum is also mentioned in the song "The Byronic Man" by British band Cradle of Filth on their 2006 album, Thornography. - Laudanum and Poitín are mentioned in the song "The Snake With Eyes of Garnet" by Shane MacGowan (Shane MacGowan and The Popes) on his 1994 album, The Snake. - Laudanum is used by the character Mrs. Sedley in Benjamin Britten's opera, Peter Grimes. - "Halcion laudanum and Opium" is a line in Josh Ritter's song "Thin Blue Flame". - In the song "I Met Everybody I Knew" by Mark Sheridan, he describes his ennui with life and wishes to end it with laudanum # Today's status Laudanum is still available by prescription in the United States. It is classified as a Schedule II drug under the Controlled Substances Act. Its most common formulation is known as "deodorized tincture of opium", (or DTO), and is manufactured in the United States by Ranbaxy Pharmaceuticals. Deodorized or "denarcotized" opium means that narcotine, one of the most prevalent alkaloids in opium, has been removed, usually by a petroleum distillate. Narcotine has no analgesic properties, and frequently causes nausea and stomach upset; hence the preference for denarcotized opium. The only medically-approved uses for laudanum in the United States are for treating diarrhea and pain. Laudanum, as deodorized opium tincture, contains the equivalent of 10 milligrams of morphine per milliliter. By contrast, laudanum's weaker cousin, paregoric, also known as camphorated tincture of opium, is 1/25th the strength of laudanum, containing only 0.4 milligrams of morphine per milliliter. Caution should be employed so as not to confuse opium tincture (laudanum) and camphorated opium tincture (paregoric), since overdose may occur if the former is used when the latter has been indicated. The United States Pharmacopia recommends that the abbreviation "DTO" never be used in place of "deodorized tincture of opium", since DTO is sometimes employed to abbreviate "diluted tincture of opium", which is a 1:25 dilution of opium tincture and water commonly employed to treat withdrawal symptoms in neonates. Further, paregoric's synonym "camphorated tincture of opium" should not be used, since it could easily be confused with "tincture of opium" or "deodorized tincture of opium." The usual adult dosage of laudanum for the treatment of diarrhea is 0.6 mL (equivalent to 6 mg of morphine) four times a day. There is no maximum dose; refractory cases (e.g. diarrhea associated with AIDS) may require doses as high as 4 mL (equivalent to 40 mg of morphine) every three hours.	Laudanum Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Laudanum is an opium tincture, sometimes sweetened with sugar and also called wine of opium. # History In the 16th century, Paracelsus experimented with the medical value of opium. He decided that its medical (analgesic) value was of such magnitude that he called it Laudanum, from the Latin laudare, to praise, or from labdanum, the term for a plant extract. He did not know of its addictive properties. In the 19th century, laudanum was used in many patent medicines to "relieve pain... to produce sleep... to allay irritation... to check excessive secretions... to support the system... [and] as a sudorific".[1] The limited pharmacopoeia of the day meant that opium derivatives were among the most efficacious of available treatments, and so laudanum was widely prescribed for ailments from colds to meningitis to cardiac diseases, in both adults and children. Laudanum was used during the yellow fever epidemic. The Romantic and Victorian eras were marked by the widespread use of laudanum in Europe and the United States. Initially a working class drug, laudanum was cheaper than a bottle of gin or wine, because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage. Literary figures of note who used laudanum include: - Lord Byron[citation needed] - Jane Johnston Schoolcraft, the early American Indian writer - Kate Chopin - Samuel Taylor Coleridge, who was addicted for much of his adult life - Thomas de Quincey, who turned his addiction into literary success with the publication of Confessions of an English Opium Eater - Percy Bysshe Shelley, who suffered raging laudanum-induced hallucinations - John Keats - Lewis Carroll of which some inspiration of Alice in Wonderland could have come from - Iolo Morgannwg, the Welsh antiquarian - Charles Dickens - Antonin Artaud - Edgar Allan Poe - Charles Baudelaire[citation needed] - Branwell Brontë (brother of the Brontë sisters). - Mary Todd Lincoln, wife of President Abraham Lincoln, misprescribed for sleep problems, which caused anxiety and hallucinations. Upon increase of these hallucinations, more laudanum and chloral hydrate was administered, which increased the problem and led to her eventual commitment to an asylum. Political figures who used the drug included George Washington, William Wilberforce and Meriwether Lewis. Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches and used it to achieve the pallid complexion associated with tuberculosis (frailty and paleness were particularly prized in females at the time)[citation needed]. Nurses also spoon-fed laudanum to infants. The Pre-Raphaelite muse Elizabeth Siddal died of a laudanum overdose. # Depictions in fiction ## Literature - In William Faulkner's novel "Pylon", the reporter tries to buy absinthe, but is given gin with laudanum in it. - In Thomas Harris's novel Hannibal Rising, Hannibal Lecter is asked by a condemned prisoner to give him laudanum before facing death by guillotine, in exchange for allowing his body to be used in a Paris medical school. It is later suggested that this was common practice at the time. - In Patrick O'Brian's Aubrey–Maturin series of novels, the ship's surgeon, Stephen Maturin, both uses the drug professionally and battles his own addiction to it. - In Alan Moore's The League of Extraordinary Gentlemen, Allan Quatermain, opium-addicted, uses his bottle of laudanum to paralyze Edward Hyde. - In Joanne Harris's 1993 novel Sleep Pale Sister, Effie was fed laudanum to keep her out of "hysterics" and also so that she could sleep. - The character of Oscar Hopkins in Peter Carey's novel Oscar and Lucinda (1988) uses laudanum, initially under duress, to dull his hydrophobia during his expedition from Sydney. - Mary Shelley's character Victor Frankenstein uses laudanum to help him sleep after the death of his friend, Henry Clerval. - In E.L. Doctorow's Ragtime, Harry K. Thaw is said to have once drank an entire bottle of laudanum. - In Jack Finney's Time and Again, the main character, Si Morley, wonders if a live baby in an 1882 display case has been "doped up with one of the laudanum preparations I'd seen advertised in Harpers." - Laudanum is also used as a means to circumvent Speck magic in the Soldier Son Trilogy by Robin Hobb. - Laudanum is mentioned frequently in William S. Burroughs' Naked Lunch, and The Nova Trilogy, beginning with The Soft Machine. - In the tenth chapter of James Joyce's Ulysses, Haines is depicted drinking laudanum from a phial.[2] - In Octavia E. Butler's Kindred, Rufus' mother uses laudanum as a medicine to relieve her pain. - In Wilkie Collins' The Moonstone (1868), a valuable diamond, the Moonstone, is stolen by a character in a laudanum-induced stupor. - It is mentioned in Sarah Waters' Tipping the Velvet as a way a nanny calmed the child Cyril, and thus an argument for Nancy to stay with that family and watch the child during the day. - The character Cassy in Uncle Tom's Cabin kills one of her children with laudanum to prevent it from growing up in slavery. - Hannibal Sefton, a tuberculosis-afflicted violinist in Barbara Hambly's Benjamin January mystery series, is addicted to laudanum, and uses it as a means of self-medication. - It appears in the hard-boiled detective novels of Dashiell Hammett and Raymond Chandler, including Red Harvest and The Big Sleep, respectively. - In Charles Dickens' novel The Mystery of Edwin Drood it is the drink of choice for the sinister uncle Jasper. - In Love in the Time of Cholera by Gabriel Garcia Marquez, laudanum is the drink that America Vicuna uses to kill herself. - In One Hundred Years of Solitude by Gabriel Garcia Marquez, Amaranta decides to poison her adopted sister Rebeca with laudanum in order to prevent the latter's marriage to Pietro Crespi, whom Amaranta secretly loves. Instead, Amaranta inadvertently poisons her innocent sister-in-law Remedios Mascote. - In "Kal" by Judy Nunn, the character "Carmelina" is given laudanum by Lewis as a sexual enhancement; (p568)"Just a sip, my darling, just for fun", He'd said the first time he offered her the spoon.....and of course, she'd obeyed. - In Affinity (novel) by Sarah Waters, protagonist Margaret Prior takes laudanum as advised by her doctor. - In Cloud Atlas, one of the protagonists Adam Ewing is made to become addicted to laudanum after being fed it as medicine by another passenger without being aware of its nature. - In Bram Stoker's Dracula Lucy Westenra's maids are poisoned (though not killed) by Dracula with a dose of laudanum put into wine. - In Interview with the Vampire (from The Vampire Chronicles series by Anne Rice), Claudia gives a deadly dose of laudanum to two orphans whom Lestat is tricked into feeding upon, thus poisoning him. - In The House of the Scorpion by Nancy Farmer, the protagonist, Matt is accused of killing the dog of his friend, Maria, by adding laudanum to its meat. - In Alice Munro's short story "Meneseteung", Almeda Roth, an eccentric spinster, is imagined (by the narrator) to have taken laudanum ("Many ladies did", Munro writes.) - In Libba Bray's novels A Great and Terrible Beauty ,Rebel Angels and The Sweet Far Thing, Gemma's father is addicted to laudanum as a result of the death of his wife. - Samuel Taylor Coleridge wrote the poem fragment Kubla Khan immediately on waking from a laudanum-induced dream. - In Robery Hicks novel The Widow of the South laudanum is mentioned by Carrie McGavock as a method of controlling grief in women whose husbands and sons had gone to war. - Also in the novel Freaks: Alive, on the Inside, author Annette Curtis Klause has a character by the name of Ceecee harboring a dangerous secret of laudanum addiction. - Dirk Gently's Holistic Detective Agency by Douglas Adams references Samuel Taylor Coleridge's use of Laudanum. - In Asterix, Laudanum is one of the four Roman encampments surrounding the protagonists' village. - In the Great and Terrible Beauty novels by Libba Bray, the protagonist, Gemma, is the daughter of a laundanum addict. Her father takes up the drug after the death of his wife (her mother) Virginia. ## Film - In the 2001 movie From Hell laudanum plays an important role: Jack the Ripper is shown using it to numb his victims, while Inspector Frederick Abberline (played by Johnny Depp) uses a laudanum and absinthe mixture to see visions of the future or past. - In John Wayne's final movie The Shootist, his character J.B. Books is suffering from terminal cancer, and his doctor E.W. Hostetler (played by James Stewart) prescribes laudanum to relieve the pain. - In Amazing Grace, the William Wilberforce Story, there are numerous scenes of Wilberforce being given laudanum to relieve symptoms of colitis. - In Cold Mountain the main character Inman gets a drink with laudanum from the old woman who killed her goat to feed him. - In Master and Commander: The Far Side of the World, the doctor issues laudanum to a boy whose arm is to be amputated. - In the 1971 movie The Beguiled, Geraldine Page's character used laudanum to sedate Clint Eastwood's character when she amputated his leg. - In Shadow of the Vampire F.W. Murnau (played by John Malkovich) is discovered using laudanum by his cinematographer. - In Tombstone, Mattie Blaylock, Wyatt Earp's common law wife, is depicted as a laudanum addict, true to her real-life addiction. - In the 1995 Ang Lee adaptation of Jane Austen's Sense and Sensibility, Doctor Harris (Oliver Ford Davies) gives Laudanum to a heartbroken Marianne Dashwood (Kate Winslet) to bring down an infectious fever after she ventures out in a storm to see Willoughby's Estate. - In the movie House of Mirth, Gillian Anderson's character Lily Bart uses laudanum to escape her troubles. - In the film Interview with the Vampire: The Vampire Chronicles, Claudia poisons two young boys with laudanum to keep their blood warm and fool Lestat into drinking from them. ## Television - Alma Garrett (played by Molly Parker) was addicted to laudanum in Deadwood. - In the Hornblower television movies "The Mutiny" and "Retribution", Dr. Clive (played by David Rintoul) freely dispensed laudanum to injured or beaten seamen, to the mentally unstable Captain Sawyer (played by David Warner), and to himself. - In an episode of the Little House on the Prairie television series titled "Blizzard", several children are experiencing pain in their hands and feet as they are warmed up in the schoolhouse after suffering from partial hypothermia and frostbite. To help them with the pain, Dr. Baker issues laudanum, but "just half a teaspoon!". - In the first episode of the 19th season of The Simpsons, entitled "He Loves To Fly And He D'oh's", Mr. Burns has a shopping list on which "Laudanum" is first on the list. Followed by: "cotton gin", "spats", "cell phone" and "Brooklyn Dodgers." - In episode seven of the first season of Bramwell, Lady Cora Peters (played by actress Michele Dotrice) suffered acute stomach pains which turned out to be appendicitis inaccurately diagnosed as tifilitis by her doctor who prescribed a small bottle of laudanum to ease her pain. ## Music - laudanum is the french electronic project of Matthieu Malon who releases several singles & also 2 albums with that name : system:on in 2002 & your place & time will be mine in 2006. his myspace page & his label. - Avec Laudenum is the title of the fifth release by the ambient group Stars of the Lid. - "Laudanum" is the title of the fifth track on the CD Wholesale Meats and Fish by Letters to Cleo. - Laudanum is mentioned in the song "The Legionnaire's Lament" by The Decemberists. - Laudanum is the name of a song by Montreal Guitar Prodigy Domininc Cifarelli's "The Chronicles of Israfel" - Laudanum is also mentioned in the song "The Byronic Man" by British band Cradle of Filth on their 2006 album, Thornography. - Laudanum and Poitín are mentioned in the song "The Snake With Eyes of Garnet" by Shane MacGowan (Shane MacGowan and The Popes) on his 1994 album, The Snake. - Laudanum is used by the character Mrs. Sedley in Benjamin Britten's opera, Peter Grimes. - "Halcion laudanum and Opium" is a line in Josh Ritter's song "Thin Blue Flame". - In the song "I Met Everybody I Knew" by Mark Sheridan, he describes his ennui with life and wishes to end it with laudanum # Today's status Laudanum is still available by prescription in the United States. It is classified as a Schedule II drug under the Controlled Substances Act. Its most common formulation is known as "deodorized tincture of opium", (or DTO), and is manufactured in the United States by Ranbaxy Pharmaceuticals. Deodorized or "denarcotized" opium means that narcotine, one of the most prevalent alkaloids in opium, has been removed, usually by a petroleum distillate. Narcotine has no analgesic properties, and frequently causes nausea and stomach upset; hence the preference for denarcotized opium[citation needed]. The only medically-approved uses for laudanum in the United States are for treating diarrhea and pain. Laudanum, as deodorized opium tincture, contains the equivalent of 10 milligrams of morphine per milliliter. By contrast, laudanum's weaker cousin, paregoric, also known as camphorated tincture of opium, is 1/25th the strength of laudanum, containing only 0.4 milligrams of morphine per milliliter. Caution should be employed so as not to confuse opium tincture (laudanum) and camphorated opium tincture (paregoric), since overdose may occur if the former is used when the latter has been indicated. The United States Pharmacopia recommends that the abbreviation "DTO" never be used in place of "deodorized tincture of opium", since DTO is sometimes employed to abbreviate "diluted tincture of opium", which is a 1:25 dilution of opium tincture and water commonly employed to treat withdrawal symptoms in neonates.[3] Further, paregoric's synonym "camphorated tincture of opium" should not be used, since it could easily be confused with "tincture of opium" or "deodorized tincture of opium." The usual adult dosage of laudanum for the treatment of diarrhea is 0.6 mL (equivalent to 6 mg of morphine) four times a day. There is no maximum dose; refractory cases (e.g. diarrhea associated with AIDS) may require doses as high as 4 mL (equivalent to 40 mg of morphine) every three hours.[citation needed]	https://www.wikidoc.org/index.php/Laudanum
8a2c2dfcfc03dc10c2683bd651c36aa16d6f90fd	wikidoc	Lavender	Lavender The Lavenders Lavandula are a genus of about 25-30 species of flowering plants in the mint family, Lamiaceae, native to the Mediterranean region south to tropical Africa and to the southeast regions of India. The genus includes annuals, herbaceous plants, subshrubs, and small shrubs. The native range extends across the Canary Islands, North and East Africa, south Europe and the Mediterranean, Arabia, and India. Because the cultivated forms are planted in gardens world-wide, they are occasionally found growing wild, as garden escapees, well beyond their natural range. # Uses The most common species in cultivation is the Common Lavender Lavandula angustifolia (formerly L. officinalis). A wide range of cultivars can be found. Other commonly grown ornamental species are L. stoechas, L. dentata, and L. multifida. Lavenders are widely grown in gardens. Flower spikes are used for dried flower arrangements. The fragrant, pale purple flowers and flower buds are used in potpourris. Dried and sealed in pouches, they are placed among stored items of clothing to give a fresh fragrance and as a deterrent to moths. The plant is also grown commercially for extraction of lavender oil from the flowers. This oil is used as an antiseptic and for aromatherapy. Lavender flowers yield abundant nectar which yields a high quality honey for beekeepers. Lavender monofloral honey is produced primarily in the nations around the Mediterranean, and marketed worldwide as a premium product. Lavender flowers can be candied and are used as cake decoration. Lavender is also used as a herb, either alone or as an ingredient of herbes de Provence. Lavender is also used to flavour sugar, the product being called "lavender sugar", and the flowers are sometimes sold in a blend with black tea, as "lavender tea". French chefs in and around Provence, France have been incorporating this herb into their cuisine for many centuries. Lavender lends a floral, slightly sweet and elegant flavour to most dishes. For most cooking applications it is the dried buds (also referred to as flowers) of lavender that are utilised, though some chefs experiment with the leaves as well. It is the buds however that contain the essential oil of lavender, which is where both the scent and flavour of lavender are best derived. ## Medicinal use Lavender has been used extensively in herbalism. English lavender, Lavandula angustifolia, yields a highly effective essential oil with very sweet overtones, and can be used in balms, salves, perfumes, cosmetics, and topical applications. Lavandin, Lavandula x intermedia (also known as French lavender), yields a similar essential oil, but with higher levels of terpenes including camphor, which add a sharper overtone to the fragrance. Spanish lavender, Lavandula stoechas is not used medicinally, but mainly for landscaping purposes. Essential oil of lavender has antiseptic and anti-inflammatory properties. It was used in hospitals during WWI to disinfect floors, walls and other surfaces. An infusion of lavender is claimed to soothe and heal insect bites. Bunches of lavender are also said to ward off insects. If applied to the temples, lavender oil is said to soothe headaches. Lavender is frequently used as an aid to sleep and relaxation: Seeds and flowers of the plant are added to pillows, and an infusion of three flowerheads added to a cup of boiling water are recommended as a soothing and relaxing bedtime drink. Lavender oil (or extract of Lavender) is claimed to heal acne when used diluted 1:10 with water, rosewater, or witch hazel; it is also used in the treatment of skin burns and inflammatory conditions (it is a traditional treatment for these in Iran). Health precautions: There is scientific evidence to support the effectiveness of some of these remedies, especially the anti-inflammatory effects, but they should be used with caution since lavender oil can also be a powerful allergen. Ingesting lavender should be avoided during pregnancy and breastfeeding.. Topically, lavender oil is cytotoxic as well as photosensitizing. A study demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25%. Linalool, a component of lavender oil, reflected the activity of the whole oil, indicating that linalool may be the active component of lavender oil . The result of another study study showed that aqueous extracts reduced mitotic index, but induced chromosome aberrations and mitotic aberrations in comparison with control, significantly. Aqueous extracts induced breaks, stickiness, pole deviations and micronuclei. Furthermore, these effects were related to extract concentrations . ## Gynaecomastia Two essential oils, lavender and tea tree oil, have been implicated in causing gynaecomastia, an abnormal breast tissue growth in prepubescent boys. An article in the New England Journal of Medicine claimed that the use of shampoo and similar products, containing lavender and tea tree oils, in three boys resulted in this condition. The authors were contacted, but have refused to identify the products used or discuss their work further. General knowledge of the formulas of such products, however, suggests that the levels of these materials could not have exceeded a few tenths of one percent--certainly not enough to produce any kind of adverse effects. However, a child hormone specialist at the University of Cambridge has claimed "... these oils can mimic oestrogens" and "people should be a little bit careful about using these products". # History The ancient Greeks called the lavender herb nardus, after the Syrian city of Naarda. It was also commonly called nard. During Roman times, flowers were sold for 100 denarii per pound, which was about the same as a month's wages for a farm labourer, or fifty haircuts from the local barber. Lavender was commonly used in Roman baths to scent the water, and it was thought to restore the skin. Its late Latin name was lavandārius, from lavanda (things to be washed), from the verb lavāre (to wash). When the Roman Empire conquered southern Britain, the Romans introduced lavender. During the height of the Plague, glove makers at Grasse would scent their leathers with lavender oil, and this was claimed to ward off the Plague. This story could have some validity as the Plague was transmitted by fleas, which lavender is known to repel. Former Manchester United striker Ruud Van Nistelrooy advocates the use of Lavender, and has been said to coat his boots in it prior to sleep.	Lavender The Lavenders Lavandula are a genus of about 25-30 species of flowering plants in the mint family, Lamiaceae, native to the Mediterranean region south to tropical Africa and to the southeast regions of India. The genus includes annuals, herbaceous plants, subshrubs, and small shrubs. The native range extends across the Canary Islands, North and East Africa, south Europe and the Mediterranean, Arabia, and India. Because the cultivated forms are planted in gardens world-wide, they are occasionally found growing wild, as garden escapees, well beyond their natural range. # Uses The most common species in cultivation is the Common Lavender Lavandula angustifolia (formerly L. officinalis). A wide range of cultivars can be found. Other commonly grown ornamental species are L. stoechas, L. dentata, and L. multifida. Lavenders are widely grown in gardens. Flower spikes are used for dried flower arrangements. The fragrant, pale purple flowers and flower buds are used in potpourris. Dried and sealed in pouches, they are placed among stored items of clothing to give a fresh fragrance and as a deterrent to moths. The plant is also grown commercially for extraction of lavender oil from the flowers. This oil is used as an antiseptic and for aromatherapy. Lavender flowers yield abundant nectar which yields a high quality honey for beekeepers. Lavender monofloral honey is produced primarily in the nations around the Mediterranean, and marketed worldwide as a premium product. Lavender flowers can be candied and are used as cake decoration. Lavender is also used as a herb, either alone or as an ingredient of herbes de Provence. Lavender is also used to flavour sugar, the product being called "lavender sugar", and the flowers are sometimes sold in a blend with black tea, as "lavender tea". French chefs in and around Provence, France have been incorporating this herb into their cuisine for many centuries. Lavender lends a floral, slightly sweet and elegant flavour to most dishes. For most cooking applications it is the dried buds (also referred to as flowers) of lavender that are utilised, though some chefs experiment with the leaves as well. It is the buds however that contain the essential oil of lavender, which is where both the scent and flavour of lavender are best derived. ## Medicinal use Lavender has been used extensively in herbalism. English lavender, Lavandula angustifolia, yields a highly effective essential oil with very sweet overtones, and can be used in balms, salves, perfumes, cosmetics, and topical applications. Lavandin, Lavandula x intermedia (also known as French lavender), yields a similar essential oil, but with higher levels of terpenes including camphor, which add a sharper overtone to the fragrance. Spanish lavender, Lavandula stoechas is not used medicinally, but mainly for landscaping purposes. Essential oil of lavender has antiseptic and anti-inflammatory properties. It was used in hospitals during WWI to disinfect floors, walls and other surfaces. An infusion of lavender is claimed to soothe and heal insect bites. Bunches of lavender are also said to ward off insects. If applied to the temples, lavender oil is said to soothe headaches. Lavender is frequently used as an aid to sleep and relaxation: Seeds and flowers of the plant are added to pillows, and an infusion of three flowerheads added to a cup of boiling water are recommended as a soothing and relaxing bedtime drink. Lavender oil (or extract of Lavender) is claimed to heal acne when used diluted 1:10 with water, rosewater, or witch hazel; it is also used in the treatment of skin burns and inflammatory conditions (it is a traditional treatment for these in Iran). Health precautions: There is scientific evidence to support the effectiveness of some of these remedies, especially the anti-inflammatory effects, but they should be used with caution since lavender oil can also be a powerful allergen. Ingesting lavender should be avoided during pregnancy and breastfeeding.[1]. Topically, lavender oil is cytotoxic as well as photosensitizing. A study demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25%. Linalool, a component of lavender oil, reflected the activity of the whole oil, indicating that linalool may be the active component of lavender oil [2]. The result of another study study showed that aqueous extracts reduced mitotic index, but induced chromosome aberrations and mitotic aberrations in comparison with control, significantly. Aqueous extracts induced breaks, stickiness, pole deviations and micronuclei. Furthermore, these effects were related to extract concentrations [3]. ## Gynaecomastia Two essential oils, lavender and tea tree oil, have been implicated in causing gynaecomastia, an abnormal breast tissue growth in prepubescent boys. An article in the New England Journal of Medicine claimed that the use of shampoo and similar products, containing lavender and tea tree oils, in three boys resulted in this condition.[4] The authors were contacted, but have refused to identify the products used or discuss their work further. General knowledge of the formulas of such products, however, suggests that the levels of these materials could not have exceeded a few tenths of one percent--certainly not enough to produce any kind of adverse effects. However, a child hormone specialist at the University of Cambridge has claimed "... these oils can mimic oestrogens" and "people should be a little bit careful about using these products". [5][6] # History Template:Refimprovesect The ancient Greeks called the lavender herb nardus, after the Syrian city of Naarda. It was also commonly called nard.[citation needed] During Roman times, flowers were sold for 100 denarii per pound, which was about the same as a month's wages for a farm labourer, or fifty haircuts from the local barber. Lavender was commonly used in Roman baths to scent the water, and it was thought to restore the skin.[citation needed] Its late Latin name was lavandārius, from lavanda (things to be washed), from the verb lavāre (to wash).[7] When the Roman Empire conquered southern Britain, the Romans introduced lavender.[citation needed] During the height of the Plague, glove makers at Grasse would scent their leathers with lavender oil, and this was claimed to ward off the Plague. This story could have some validity as the Plague was transmitted by fleas, which lavender is known to repel.[citation needed] Former Manchester United striker Ruud Van Nistelrooy advocates the use of Lavender, and has been said to coat his boots in it prior to sleep.[citation needed]	https://www.wikidoc.org/index.php/Lavender
4252337e27e79b4fb27fcd0c6890109ffd6227a3	wikidoc	Learning	Learning Learning is the acquisition and development of memories and behaviors, including skills, knowledge, understanding, values, and wisdom. It is the product of experience and the goal of education. Learning ranges from simple forms of learning such as habituation and classical conditioning seen in many animal species, to more complex activities such as play, seen only in relatively intelligent animals. # Physiology of learning "Thought," in a general sense, is commonly conceived as something arising from the stimulation of neurons in the brain. Current understanding of neurons and the central nervous system implies that the process of learning corresponds to changes in the relationship between certain neurons in the brain. Research is ongoing in this area. It is generally recognized that memory is more easily retained when multiple parts of the brain are stimulated, such as through combinations of hearing, seeing, smelling, motor skills, touch sense, and logical thinking. Repeating thoughts and actions is an essential part of learning. Thinking about a specific memory will make it easy to recall. This is the reason why reviews are such an integral part of education. On first performing a task, it is difficult as there is no path from axon to dendrite. After several repetitions a pathway begins to form and the task becomes easier. When the task becomes so easy that you can perform it at any time, the pathway is fully formed. The speed at which a pathway is formed depends on the individual, but is usually localised resulting in talents. # Types of learning ## Simple non-associative learning ### Habituation In psychology, habituation is an example of non-associative learning in which there is a progressive diminution of behavioral response probability with repetition of a stimulus. It is another form of integration. An animal first responds to a stimulus, but if it is neither rewarding nor harmful the animal reduces subsequent responses. One example of this can be seen in small song birds - if a stuffed owl (or similar predator) is put into the cage, the birds initially react to it as though it were a real predator. Soon the birds react less, showing habituation. If another stuffed owl is introduced (or the same one removed and re-introduced), the birds react to it as though it were a predator, showing that it is only a very specific stimulus that is habituated to (namely, one particular unmoving owl in one place). Habituation has been shown in essentially every species of animal, including the large protozoan Stentor coeruleus. ### Sensitization Sensitization is an example of non-associative learning in which the progressive amplification of a response follows repeated administrations of a stimulus (Bell et al., 1995). An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm continuously. After a while, this stimulation will create a warm sensation that will eventually turn painful. The pain is the result of the progressively amplified synaptic response of the peripheral nerves warning the person that the stimulation is harmful. Sensitization is thought to underlie both adaptive as well as maladaptive learning processes in the organism. ## Associative learning ### Operant conditioning Operant conditioning is the use of consequences to modify the occurrence and form of behavior. Operant conditioning is distinguished from Pavlovian conditioning in that operant conditioning deals with the modification of voluntary behavior. Discrimination learning is a major form of operant conditioning. One form of it is called Errorless learning. ### Classical conditioning The typical paradigm for classical conditioning involves repeatedly pairing an unconditioned stimulus (which unfailingly evokes a particular response) with another stimulus (which does not normally evoke the response). Following conditioning, the response occurs both to the unconditioned stimulus and to the other, unrelated stimulus (now referred to as the "conditioned stimulus"). The response to the conditioned stimulus is termed a conditioned response. ## Imprinting Imprinting is the term used in psychology and ethology to describe any kind of phase-sensitive learning (learning occurring at a particular age or a particular life stage) that is rapid and apparently independent of the consequences of behavior. It was first used to describe situations in which an animal or person learns the characteristics of some stimulus, which is therefore said to be "imprinted" onto the subject. ## Observational learning The most basic learning process is imitation; one's personal repetition of an observed process, such as a smile. Thus an imitation will take one's time (attention to the details), space (a location for learning), skills (or practice), and other resources (for example, a protected area). Through copying, most infants learn how to hunt (i.e., direct one's attention), feed and perform most basic tasks necessary for survival. ## Play Play generally describes behavior which has no particular end in itself, but improves performance in similar situations in the future. This is seen in a wide variety of vertebrates besides humans, but is mostly limited to mammals and birds. Cats are known to play with a ball of string when young, which gives them experience with catching prey. Besides inanimate objects, animals may play with other members of their own species or other animals, such as orcas playing with seals they have caught. Play involves a significant cost to animals, such as increased vulnerability to predators and the risk or injury and possibly infection. It also consumes energy, so there must be significant benefits associated with play for it to have evolved. Play is generally seen in younger animals, suggesting a link with learning. However, it may also have other benefits not associated directly with learning, for example improving physical fitness. ## Multimedia learning The learning associated with multimedia learning environments (Mayer, 2001). This type of learning relies of dual-coding theory (Paivio, 1971). ## Electronic learning Electronic learning or E-learning is a general term used to refer to computer-enhanced learning. # Machine learning Although learning is often thought of as a property associated with living things, computers are also able to modify their own behaviors as a result of experiences. Known as machine learning, this is a broad subfield of artificial intelligence concerned with the design and development of algorithms and techniques that allow computers to "learn". At a general level, there are two types of learning: inductive, and deductive. Inductive machine learning methods extract rules and patterns out of massive data sets. The major focus of machine learning research is to extract information from data automatically, by computational and statistical methods. Hence, machine learning is closely related to data mining and statistics but also theoretical computer science. Machine learning has a wide spectrum of applications including natural language processing, syntactic pattern recognition, search engines, medical diagnosis, bioinformatics and cheminformatics, detecting credit card fraud, stock market analysis, classifying DNA sequences, speech and handwriting recognition, object recognition in computer vision, game playing and robot locomotion. # Approaches to learning ## Rote learning Rote learning is a technique which avoids understanding the inner complexities and inferences of the subject that is being learned and instead focuses on memorizing the material so that it can be recalled by the learner exactly the way it was read or heard. The major practice involved in rote learning techniques is learning by repetition, based on the idea that one will be able to quickly recall the meaning of the material the more it is repeated. Rote learning is used in diverse areas, from mathematics to music to religion. Although it has been criticized by some schools of thought, rote learning is a necessity in many situations. ## Informal learning Informal learning occurs through the experience of day-to-day situations (for example, one would learn to look ahead while walking because of the danger inherent in not paying attention to where one is going). It is learning from life, during a meal at table with parents, Play, exploring. ## Formal learning Formal learning is learning that takes place within a teacher-student relationship, such as in a school system. Non-formal learning is organized learning outside the formal learning system. For example: learning by coming together with people with similar interests and exchanging viewpoints, in clubs or in (international) youth organisations, workshops. ## Non-formal learning and combined approaches The educational system may use a combination of formal, informal, and non-formal learning methods. The UN and EU recognize these different forms of learning (cf. links below). In some schools students can get points that count in the formal-learning systems if they get work done in informal-learning circuits. They may be given time to assist international youth workshops and training courses, on the condition they prepare, contribute, share and can proof this offered valuable new insights, helped to acquire new skills, a place to get experience in organising, teaching, etc. In order to learn a skill, such as solving a Rubik's cube quickly, several factors come into play at once: - Directions help one learn the patterns of solving a Rubik's cube - Practicing the moves repeatedly and for extended time helps with "muscle memory" and therefore speed - Thinking critically about moves helps find shortcuts, which in turn helps to speed up future attempts. - The Rubik's cube's six colors help anchor solving it within the head. - Occasionally revisiting the cube helps prevent loss of skill	Learning Template:Cleanup Template:Neuropsychology Learning is the acquisition and development of memories and behaviors, including skills, knowledge, understanding, values, and wisdom. It is the product of experience and the goal of education. Learning ranges from simple forms of learning such as habituation and classical conditioning seen in many animal species, to more complex activities such as play, seen only in relatively intelligent animals.[1][2] # Physiology of learning "Thought," in a general sense, is commonly conceived as something arising from the stimulation of neurons in the brain. Current understanding of neurons and the central nervous system implies that the process of learning corresponds to changes in the relationship between certain neurons in the brain. Research is ongoing in this area.[citation needed] It is generally recognized that memory is more easily retained when multiple parts of the brain are stimulated, such as through combinations of hearing, seeing, smelling, motor skills, touch sense, and logical thinking.[citation needed] Repeating thoughts and actions is an essential part of learning. Thinking about a specific memory will make it easy to recall. This is the reason why reviews are such an integral part of education. On first performing a task, it is difficult as there is no path from axon to dendrite. After several repetitions a pathway begins to form and the task becomes easier. When the task becomes so easy that you can perform it at any time, the pathway is fully formed. The speed at which a pathway is formed depends on the individual, but is usually localised resulting in talents.[citation needed] # Types of learning ## Simple non-associative learning ### Habituation In psychology, habituation is an example of non-associative learning in which there is a progressive diminution of behavioral response probability with repetition of a stimulus. It is another form of integration. An animal first responds to a stimulus, but if it is neither rewarding nor harmful the animal reduces subsequent responses. One example of this can be seen in small song birds - if a stuffed owl (or similar predator) is put into the cage, the birds initially react to it as though it were a real predator. Soon the birds react less, showing habituation. If another stuffed owl is introduced (or the same one removed and re-introduced), the birds react to it as though it were a predator, showing that it is only a very specific stimulus that is habituated to (namely, one particular unmoving owl in one place). Habituation has been shown in essentially every species of animal, including the large protozoan Stentor coeruleus.[3] ### Sensitization Sensitization is an example of non-associative learning in which the progressive amplification of a response follows repeated administrations of a stimulus (Bell et al., 1995). An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm continuously. After a while, this stimulation will create a warm sensation that will eventually turn painful. The pain is the result of the progressively amplified synaptic response of the peripheral nerves warning the person that the stimulation is harmful. Sensitization is thought to underlie both adaptive as well as maladaptive learning processes in the organism. ## Associative learning ### Operant conditioning Operant conditioning is the use of consequences to modify the occurrence and form of behavior. Operant conditioning is distinguished from Pavlovian conditioning in that operant conditioning deals with the modification of voluntary behavior. Discrimination learning is a major form of operant conditioning. One form of it is called Errorless learning. ### Classical conditioning The typical paradigm for classical conditioning involves repeatedly pairing an unconditioned stimulus (which unfailingly evokes a particular response) with another stimulus (which does not normally evoke the response). Following conditioning, the response occurs both to the unconditioned stimulus and to the other, unrelated stimulus (now referred to as the "conditioned stimulus"). The response to the conditioned stimulus is termed a conditioned response. ## Imprinting Template:Section stub Imprinting is the term used in psychology and ethology to describe any kind of phase-sensitive learning (learning occurring at a particular age or a particular life stage) that is rapid and apparently independent of the consequences of behavior. It was first used to describe situations in which an animal or person learns the characteristics of some stimulus, which is therefore said to be "imprinted" onto the subject. ## Observational learning The most basic learning process is imitation; one's personal repetition of an observed process, such as a smile. Thus an imitation will take one's time (attention to the details), space (a location for learning), skills (or practice), and other resources (for example, a protected area). Through copying, most infants learn how to hunt (i.e., direct one's attention), feed and perform most basic tasks necessary for survival. ## Play Play generally describes behavior which has no particular end in itself, but improves performance in similar situations in the future. This is seen in a wide variety of vertebrates besides humans, but is mostly limited to mammals and birds. Cats are known to play with a ball of string when young, which gives them experience with catching prey. Besides inanimate objects, animals may play with other members of their own species or other animals, such as orcas playing with seals they have caught. Play involves a significant cost to animals, such as increased vulnerability to predators and the risk or injury and possibly infection. It also consumes energy, so there must be significant benefits associated with play for it to have evolved. Play is generally seen in younger animals, suggesting a link with learning. However, it may also have other benefits not associated directly with learning, for example improving physical fitness. ## Multimedia learning The learning associated with multimedia learning environments (Mayer, 2001). This type of learning relies of dual-coding theory (Paivio, 1971). ## Electronic learning Electronic learning or E-learning is a general term used to refer to computer-enhanced learning. # Machine learning Although learning is often thought of as a property associated with living things, computers are also able to modify their own behaviors as a result of experiences. Known as machine learning, this is a broad subfield of artificial intelligence concerned with the design and development of algorithms and techniques that allow computers to "learn". At a general level, there are two types of learning: inductive, and deductive. Inductive machine learning methods extract rules and patterns out of massive data sets. The major focus of machine learning research is to extract information from data automatically, by computational and statistical methods. Hence, machine learning is closely related to data mining and statistics but also theoretical computer science. Machine learning has a wide spectrum of applications including natural language processing, syntactic pattern recognition, search engines, medical diagnosis, bioinformatics and cheminformatics, detecting credit card fraud, stock market analysis, classifying DNA sequences, speech and handwriting recognition, object recognition in computer vision, game playing and robot locomotion. # Approaches to learning ## Rote learning Rote learning is a technique which avoids understanding the inner complexities and inferences of the subject that is being learned and instead focuses on memorizing the material so that it can be recalled by the learner exactly the way it was read or heard. The major practice involved in rote learning techniques is learning by repetition, based on the idea that one will be able to quickly recall the meaning of the material the more it is repeated. Rote learning is used in diverse areas, from mathematics to music to religion. Although it has been criticized by some schools of thought, rote learning is a necessity in many situations. ## Informal learning Informal learning occurs through the experience of day-to-day situations (for example, one would learn to look ahead while walking because of the danger inherent in not paying attention to where one is going). It is learning from life, during a meal at table with parents, Play, exploring. ## Formal learning Formal learning is learning that takes place within a teacher-student relationship, such as in a school system. Non-formal learning is organized learning outside the formal learning system. For example: learning by coming together with people with similar interests and exchanging viewpoints, in clubs or in (international) youth organisations, workshops. ## Non-formal learning and combined approaches The educational system may use a combination of formal, informal, and non-formal learning methods. The UN and EU recognize these different forms of learning (cf. links below). In some schools students can get points that count in the formal-learning systems if they get work done in informal-learning circuits. They may be given time to assist international youth workshops and training courses, on the condition they prepare, contribute, share and can proof this offered valuable new insights, helped to acquire new skills, a place to get experience in organising, teaching, etc. In order to learn a skill, such as solving a Rubik's cube quickly, several factors come into play at once: - Directions help one learn the patterns of solving a Rubik's cube - Practicing the moves repeatedly and for extended time helps with "muscle memory" and therefore speed - Thinking critically about moves helps find shortcuts, which in turn helps to speed up future attempts. - The Rubik's cube's six colors help anchor solving it within the head. - Occasionally revisiting the cube helps prevent loss of skill	https://www.wikidoc.org/index.php/Learning
e105c54c85a5784e4117f15a175cc6608dd02642	wikidoc	Lecithin	Lecithin # Overview Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol). Lecithin was first isolated in 1846 by the French chemist and pharmacist Theodore Gobley. In 1850, he named the phosphatidylcholine lécithine. Gobley originally isolated lecithin from egg yolk—λέκιθος lekithos is "egg yolk" in Ancient Greek—and established the complete chemical formula of phosphatidylcholine in 1874; in between, he had demonstrated the presence of lecithin in a variety of biological matters, including venous blood, bile, human brain tissue, fish eggs, fish roe, and chicken and sheep brain. Lecithin can easily be extracted chemically (using hexane, ethanol, acetone, petroleum ether, benzene, etc.) or mechanically. It is usually available from sources such as soybeans, eggs, milk, marine sources, rapeseed, cottonseed, and sunflower. It has low solubility in water, but is an excellent emulsifier. In aqueous solution, its phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature. This results in a type of surfactant that usually is classified as amphipathic. Lecithin is sold as a food supplement and for medical uses. In cooking, it is sometimes used as an emulsifier and to prevent sticking, for example in nonstick cooking spray. # Biology Lecithin, as a food additive, is also a dietary source of several active compounds: Choline and its metabolites are needed for several physiological purposes, including cell membrane signaling and cholinergic neurotransmission, and is a major source for methyl groups via its metabolite, trimethylglycine (betaine). Phosphatidylcholine occurs in all cellular organisms, being one of the major components of the phospholipid portion of the cell membrane. While lecitihin is also a rich source of a variety of types of dietary fats, the small amounts of lecithin typically used for food additive purposes mean it is not a significant source of fats. # Production Commercial lecithin, as used by food manufacturers, is a mixture of phospholipids in oil. The lecithin can be obtained by water degumming the extracted oil of seeds. It is a mixture of various phospholipids, and the composition depends on the origin of the lecithin. A major source of lecithin is soybean oil. Because of the EU requirement to declare additions of allergens in foods, in addition to regulations regarding genetically modified crops, a gradual shift to other sources of lecithin (e.g., sunflower oil) is taking place. The main phospholipids in lecithin from soya and sunflower are phosphatidyl choline, phosphatidyl inositol, phosphatidyl ethanolamine, and phosphatidic acid. They often are abbreviated to PC, PI, PE, and PA, respectively. Purified phospholipids are produced by companies commercially. ## Hydrolysed lecithin To modify the performance of lecithin to make it suitable for the product to which it is added, it may be hydrolysed enzymatically. In hydrolysed lecithins, a portion of the phospholipids have one fatty acid removed by phospholipase. Such phospholipids are called lysophospholipids. The most commonly used phospholipase is phospholipase A2, which removes the fatty acid at the C2 position of glycerol. Lecithins may also be modified by a process called fractionation. During this process, lecithin is mixed with an alcohol, usually ethanol. Some phospholipids, such as phosphatidylcholine, have good solubility in ethanol, whereas most other phospholipids do not dissolve well in ethanol. The ethanol is separated from the lecithin sludge, after which the ethanol is removed by evaporation to obtain a phosphatidylcholine-enriched lecithin fraction. ## Genetically modified crops as a source of lecithin As described above, lecithin is highly processed. Therefore, genetically modified (GM) protein or DNA from the original GM crop from which it is derived often is undetectable – in other words, it is not substantially different from lecithin derived from non-GM crops. Nonetheless, consumer concerns about genetically modified food have extended to highly purified derivatives from GM food, such as lecithin. This concern led to policy and regulatory changes in the European Union in 2000, when Commission Regulation (EC) 50/2000 was passed which required labelling of food containing additives derived from GMOs, including lecithin. Because it is nearly impossible to detect the origin of derivatives such as lecithin, the European regulations require those who wish to sell lecithin in Europe to use a meticulous system of identity preservation (IP). # Properties and applications Lecithin has emulsification and lubricant properties, and is a surfactant. It can be totally metabolized (see Inositol) by humans, so is well tolerated by humans and nontoxic when ingested; some other emulsifiers can only be excreted via the kidneys. The major components of commercial soybean-derived lecithin are: - 33–35% Soybean oil - 20–21% Inositol phosphatides - 19–21% Phosphatidylcholine - 8–20% Phosphatidylethanolamine - 5–11% Other phosphatides - 5% Free carbohydrates - 2–5% Sterols - 1% Moisture Lecithin is used for applications in human food, animal feed, pharmaceuticals, paints, and other industrial applications. Applications include: - In the pharmaceutical industry, it acts as a wetting, stabilizing agent and a choline enrichment carrier, helps in emulsifications and encapsulation, and is a good dispersing agent. It can be used in manufacture of intravenous fat infusions and for therapeutic use. - In animal feed, it enriches fat and protein and improves pelletization. - In the paint industry, it forms protective coatings for surfaces with painting and printing ink, has antioxidant properties, helps as a rust inhibitor, is a colour-intensifying agent, catalyst, conditioning aid modifier, and dispersing aid; it is a good stabilizing and suspending agent, emulsifier, and wetting agent, helps in maintaining uniform mixture of several pigments, helps in grinding of metal oxide pigments, is a spreading and mixing aid, prevents hard settling of pigments, eliminates foam in water-based paints, and helps in fast dispersion of latex-based paints. - Lecithin also may be used as a release agent for plastics, an antisludge additive in motor lubricants, an antigumming agent in gasoline, and an emulsifier, spreading agent, and antioxidant in textile, rubber, and other industries. ## Food additive The nontoxicity of lecithin leads to its use with food, as an additive or in food preparation. It is used commercially in foods requiring a natural emulsifier or lubricant. In confectionery, it reduces viscosity, replaces more expensive ingredients, controls sugar crystallization and the flow properties of chocolate, helps in the homogeneous mixing of ingredients, improves shelf life for some products, and can be used as a coating. In emulsions and fat spreads, it stabilizes emulsions, reduces spattering during frying, improves texture of spreads and flavour release. In doughs and bakery, it reduces fat and egg requirements, helps even distribution of ingredients in dough, stabilizes fermentation, increases volume, protects yeast cells in dough when frozen, and acts as a releasing agent to prevent sticking and simplify cleaning. It improves wetting properties of hydrophilic powders (e.g., low-fat proteins) and lipophilic powders (e.g., cocoa powder), controls dust, and helps complete dispersion in water. Lecithin keeps cocoa and cocoa butter in a candy bar from separating. It can be used as a component of cooking sprays to prevent sticking and as a releasing agent. In margarines, especially those containing high levels of fat (>75%), lecithin is added as an 'antispattering' agent for shallow frying. Lecithin is approved by the United States Food and Drug Administration for human consumption with the status "generally recognized as safe". Lecithin is admitted by the EU as a food additive, designated as E322. Research studies show soy-derived lecithin has significant effects on lowering serum cholesterol and triglycerides, while increasing HDL ("good cholesterol") levels in the blood of rats. ## Dietary supplement Because it contains phosphatidylcholines, lecithin is a source of choline, an essential nutrient. Clinical studies have shown benefit in acne, in improving liver function, and in lowering cholesterol, but clinical studies in dementia and dyskinesias have found no benefit. An earlier study using a small sample (20 men divided in 3 groups) did not detect statistically significant short term (2-4 weeks) effects on cholesterol in hyperlipidaemic men. La Leche League recommends its use to prevent blocked or plugged milk ducts which can lead to mastitis in breastfeeding women. ## Compatibility with special diets Egg-derived lecithin is not usually a concern for those allergic to eggs since commercially available egg lecithin is highly purified and devoid of allergy-causing egg proteins. Egg lecithin is not a concern for those on low-cholesterol diets, because the lecithin found in eggs markedly inhibits the absorption of the cholesterol contained in eggs. ## Possible link to heart disease A growing body of evidence indicates lecithin is converted by gut bacteria into trimethylamine-N-oxide(TMAO), which is released into circulation, and may with time contribute to atherosclerosis and heart attacks. ## Religious restrictions Soy-derived lecithin is considered by some to be kitniyot and prohibited on Passover for Ashkenazi Jews when many grain-based foods are forbidden, but not at other times. This does not necessarily affect Sephardi Jews, who do not have the same restrictions on rice and kitniyot during Pesach/Passover. Muslims are not forbidden to eat lecithin per se; however, since it may be derived from animal as well as plant sources, care must be taken to ensure this source is halal. Lecithin derived from plants and egg yolks is permissible, as is that derived from animals slaughtered according to the rules of dhabihah.	Lecithin Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol). Lecithin was first isolated in 1846 by the French chemist and pharmacist Theodore Gobley.[1] In 1850, he named the phosphatidylcholine lécithine.[2] Gobley originally isolated lecithin from egg yolk—λέκιθος lekithos is "egg yolk" in Ancient Greek—and established the complete chemical formula of phosphatidylcholine in 1874;[3] in between, he had demonstrated the presence of lecithin in a variety of biological matters, including venous blood, bile, human brain tissue, fish eggs, fish roe, and chicken and sheep brain. Lecithin can easily be extracted chemically (using hexane, ethanol, acetone, petroleum ether, benzene, etc.) or mechanically. It is usually available from sources such as soybeans, eggs, milk, marine sources, rapeseed, cottonseed, and sunflower. It has low solubility in water, but is an excellent emulsifier. In aqueous solution, its phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature. This results in a type of surfactant that usually is classified as amphipathic. Lecithin is sold as a food supplement and for medical uses. In cooking, it is sometimes used as an emulsifier and to prevent sticking, for example in nonstick cooking spray. # Biology Template:Unsourced Lecithin, as a food additive, is also a dietary source of several active compounds: Choline and its metabolites are needed for several physiological purposes, including cell membrane signaling and cholinergic neurotransmission, and is a major source for methyl groups via its metabolite, trimethylglycine (betaine). Phosphatidylcholine occurs in all cellular organisms, being one of the major components of the phospholipid portion of the cell membrane. While lecitihin is also a rich source of a variety of types of dietary fats, the small amounts of lecithin typically used for food additive purposes mean it is not a significant source of fats. # Production Commercial lecithin, as used by food manufacturers, is a mixture of phospholipids in oil. The lecithin can be obtained by water degumming the extracted oil of seeds. It is a mixture of various phospholipids, and the composition depends on the origin of the lecithin. A major source of lecithin is soybean oil. Because of the EU requirement to declare additions of allergens in foods, in addition to regulations regarding genetically modified crops, a gradual shift to other sources of lecithin (e.g., sunflower oil) is taking place. The main phospholipids in lecithin from soya and sunflower are phosphatidyl choline, phosphatidyl inositol, phosphatidyl ethanolamine, and phosphatidic acid. They often are abbreviated to PC, PI, PE, and PA, respectively. Purified phospholipids are produced by companies commercially. ## Hydrolysed lecithin To modify the performance of lecithin to make it suitable for the product to which it is added, it may be hydrolysed enzymatically. In hydrolysed lecithins, a portion of the phospholipids have one fatty acid removed by phospholipase. Such phospholipids are called lysophospholipids. The most commonly used phospholipase is phospholipase A2, which removes the fatty acid at the C2 position of glycerol. Lecithins may also be modified by a process called fractionation. During this process, lecithin is mixed with an alcohol, usually ethanol. Some phospholipids, such as phosphatidylcholine, have good solubility in ethanol, whereas most other phospholipids do not dissolve well in ethanol. The ethanol is separated from the lecithin sludge, after which the ethanol is removed by evaporation to obtain a phosphatidylcholine-enriched lecithin fraction. ## Genetically modified crops as a source of lecithin As described above, lecithin is highly processed. Therefore, genetically modified (GM) protein or DNA from the original GM crop from which it is derived often is undetectable – in other words, it is not substantially different from lecithin derived from non-GM crops.[4] Nonetheless, consumer concerns about genetically modified food have extended to highly purified derivatives from GM food, such as lecithin.[5] This concern led to policy and regulatory changes in the European Union in 2000, when Commission Regulation (EC) 50/2000 was passed[6] which required labelling of food containing additives derived from GMOs, including lecithin. Because it is nearly impossible to detect the origin of derivatives such as lecithin, the European regulations require those who wish to sell lecithin in Europe to use a meticulous system of identity preservation (IP).[4][7] # Properties and applications Lecithin has emulsification and lubricant properties, and is a surfactant. It can be totally metabolized (see Inositol) by humans, so is well tolerated by humans and nontoxic when ingested; some other emulsifiers can only be excreted via the kidneys. The major components of commercial soybean-derived lecithin are:[8] - 33–35% Soybean oil - 20–21% Inositol phosphatides - 19–21% Phosphatidylcholine - 8–20% Phosphatidylethanolamine - 5–11% Other phosphatides - 5% Free carbohydrates - 2–5% Sterols - 1% Moisture Lecithin is used for applications in human food, animal feed, pharmaceuticals, paints, and other industrial applications. Applications include: - In the pharmaceutical industry, it acts as a wetting, stabilizing agent and a choline enrichment carrier, helps in emulsifications and encapsulation, and is a good dispersing agent. It can be used in manufacture of intravenous fat infusions and for therapeutic use. - In animal feed, it enriches fat and protein and improves pelletization. - In the paint industry, it forms protective coatings for surfaces with painting and printing ink, has antioxidant properties, helps as a rust inhibitor, is a colour-intensifying agent, catalyst, conditioning aid modifier, and dispersing aid; it is a good stabilizing and suspending agent, emulsifier, and wetting agent, helps in maintaining uniform mixture of several pigments, helps in grinding of metal oxide pigments, is a spreading and mixing aid, prevents hard settling of pigments, eliminates foam in water-based paints, and helps in fast dispersion of latex-based paints. - Lecithin also may be used as a release agent for plastics, an antisludge additive in motor lubricants, an antigumming agent in gasoline, and an emulsifier, spreading agent, and antioxidant in textile, rubber, and other industries. ## Food additive The nontoxicity of lecithin leads to its use with food, as an additive or in food preparation. It is used commercially in foods requiring a natural emulsifier or lubricant. In confectionery, it reduces viscosity, replaces more expensive ingredients, controls sugar crystallization and the flow properties of chocolate, helps in the homogeneous mixing of ingredients, improves shelf life for some products, and can be used as a coating. In emulsions and fat spreads, it stabilizes emulsions, reduces spattering during frying, improves texture of spreads and flavour release. In doughs and bakery, it reduces fat and egg requirements, helps even distribution of ingredients in dough, stabilizes fermentation, increases volume, protects yeast cells in dough when frozen, and acts as a releasing agent to prevent sticking and simplify cleaning. It improves wetting properties of hydrophilic powders (e.g., low-fat proteins) and lipophilic powders (e.g., cocoa powder), controls dust, and helps complete dispersion in water.[9] Lecithin keeps cocoa and cocoa butter in a candy bar from separating. It can be used as a component of cooking sprays to prevent sticking and as a releasing agent. In margarines, especially those containing high levels of fat (>75%), lecithin is added as an 'antispattering' agent for shallow frying. Lecithin is approved by the United States Food and Drug Administration for human consumption with the status "generally recognized as safe". Lecithin is admitted by the EU as a food additive, designated as E322. Research studies show soy-derived lecithin has significant effects on lowering serum cholesterol and triglycerides, while increasing HDL ("good cholesterol") levels in the blood of rats.[10][11][12] ## Dietary supplement Because it contains phosphatidylcholines, lecithin is a source of choline, an essential nutrient.[13][14] Clinical studies have shown benefit in acne, in improving liver function, and in lowering cholesterol, but clinical studies in dementia and dyskinesias have found no benefit.[14][15][16] An earlier study using a small sample (20 men divided in 3 groups) did not detect statistically significant short term (2-4 weeks) effects on cholesterol in hyperlipidaemic men.[17] La Leche League recommends its use to prevent blocked or plugged milk ducts which can lead to mastitis in breastfeeding women.[18] ## Compatibility with special diets Egg-derived lecithin is not usually a concern for those allergic to eggs since commercially available egg lecithin is highly purified and devoid of allergy-causing egg proteins.[19] Egg lecithin is not a concern for those on low-cholesterol diets, because the lecithin found in eggs markedly inhibits the absorption of the cholesterol contained in eggs.[20] ## Possible link to heart disease A growing body of evidence indicates lecithin is converted by gut bacteria into trimethylamine-N-oxide(TMAO), which is released into circulation, and may with time contribute to atherosclerosis and heart attacks.[21][22][23] ## Religious restrictions Soy-derived lecithin is considered by some to be kitniyot and prohibited on Passover for Ashkenazi Jews when many grain-based foods are forbidden, but not at other times. This does not necessarily affect Sephardi Jews, who do not have the same restrictions on rice and kitniyot during Pesach/Passover.[24] Muslims are not forbidden to eat lecithin per se; however, since it may be derived from animal as well as plant sources, care must be taken to ensure this source is halal. Lecithin derived from plants and egg yolks is permissible, as is that derived from animals slaughtered according to the rules of dhabihah.[25]	https://www.wikidoc.org/index.php/Lecithin
2c69e2a0695ee425076ed778cbbf976275e798fc	wikidoc	Lentinan	Lentinan # Overview Lentinan is an intravenous anti-tumor polysaccharide isolated from the fruit body of shiitake (Lentinula edodes). Lentinan has been approved as an adjuvant for stomach cancer in Japan since 1985. Lentinan is one of the host-mediated anti-cancer drugs which has been shown to affect host defense immune systems. # Chemistry Lentinan is a β-1,3 beta-glucan with β-1,6 branching. Molecular weight of lentinan is 500,000 Da. Specific rotation +14-22° (NaOH). # Research An in vitro experiment showed lentinan stimulated production of white blood cells in the human cell line U937. A pharmacological blend (MC-S) of lentinan, PSK, Ganoderma lucidum and Astragalus propinquus has also been shown to stimulate white blood cell production in vitro. An in vivo experiment on mice, revealed lentinan is orally active (since clinical use of the drug is administered through an IV). Limited clinical studies of cancer patients have associated lentinan with a higher survival rate, higher quality of life, and lower re-occurrence of cancer. # Formulations containing Lentinan Lentinex is a formulation featuring lentinan and is approved as a safe novel food in the EU.	Lentinan Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Lentinan is an intravenous anti-tumor polysaccharide isolated from the fruit body of shiitake (Lentinula edodes). Lentinan has been approved as an adjuvant for stomach cancer in Japan since 1985.[2] Lentinan is one of the host-mediated anti-cancer drugs which has been shown to affect host defense immune systems. # Chemistry Lentinan is a β-1,3 beta-glucan with β-1,6 branching. Molecular weight of lentinan is 500,000 Da. Specific rotation +14-22° (NaOH). # Research An in vitro experiment showed lentinan stimulated production of white blood cells in the human cell line U937.[1] A pharmacological blend (MC-S) of lentinan, PSK, Ganoderma lucidum and Astragalus propinquus has also been shown to stimulate white blood cell production in vitro.[2] An in vivo experiment on mice, revealed lentinan is orally active (since clinical use of the drug is administered through an IV).[3] Limited clinical studies of cancer patients have associated lentinan with a higher survival rate, higher quality of life, and lower re-occurrence of cancer.[4][5][6][7][8][9][10][11] # Formulations containing Lentinan Lentinex is a formulation featuring lentinan and is approved as a safe novel food in the EU.[12]	https://www.wikidoc.org/index.php/Lentinan
447db50b1626d862e7ba2699fa1a61e4f9fe08aa	wikidoc	Shiitake	Shiitake The shiitake (Lentinula edodes) is an edible mushroom native to East Asia. It is generally known in the English-speaking world by its Japanese name, shiitake Template:Audio (kanji: 椎茸; lit. "shii mushroom", from the Japanese name of the tree that provides the dead logs on which it is typically cultivated). In Chinese, it is called xiānggū (香菇, lit. "fragrant mushroom"). Two Chinese variant names for high grades of shiitake are dōnggū (Template:Zh-c, "winter mushroom") and huāgū (花菇, "flower mushroom", which has a flower-like cracking pattern on the mushroom's upper surface); both are produced at colder temperatures. Other names by which the mushroom is known in English include Chinese black mushroom and black forest mushroom. In Korean it is called pyogo (hangul: 표고; hanja: 瓢菰), in Thai they are called hed hom (เห็ดหอม, "fragrant mushroom"), and in Vietnamese they are called nấm hương ("fragrant mushroom"). The species was formerly known as Lentinus edodes and Agaricus edodes. The latter name was first applied by the English botanist Miles Joseph Berkeley in 1878. # History of cultivation Shiitake are native to China but have been grown in both Japan and China since prehistoric times. They have been cultivated for over 1000 years; the first written record of shiitake cultivation can be traced to Wu Sang Kwuang, born during the Song Dynasty (960-1127 A.D.). However, some documents record the uncultivated mushroom being eaten as early as 199 A.D. During the Ming Dynasty (1368-1644 A.D.), physician Wu Juei wrote that the mushroom could be used not only as a food but was taken as a remedy for upper respiratory diseases, poor blood circulation, liver trouble, exhaustion and weakness, and to boost qi, or life energy. It was also believed to prevent premature aging. Before 1982 the Japanese variety of these mushooms could only be grown in traditional locations using ancient methods. In the late '70s, Gary F. Leatham published a doctoral thesis based on his research on the budding and growth of the Japan Islands variety; the work helped make commercial cultivation possible world-wide, and Dr. Leatham is now known in the industry as the "Father of Shiitake farming in the USA." # Culinary use Shiitake have many uses in Chinese and Japanese cuisines. They are served in miso soup, used as the basis for a kind of vegetarian dashi, and also as an ingredient in many steamed and simmered dishes. In Thailand, they can be fried as well as steamed. Shiitake are often dried and sold as preserved food in packages. These must be rehydrated by soaking in water before using. Many people prefer dried shiitake to fresh, considering that the sun-drying process draws out the superior umami flavour from the dried mushrooms by breaking down proteins into amino acids. The stems of shiitake are rarely used in Japanese and other cuisines, primarily because the stems are harder and take longer to cook than the soft fleshy caps. The highest grade of shiitake are called donko in Japanese. Today, Shiitake mushrooms have become popular in many other countries as well. Russia produces and also consumes large amounts of them, mostly sold pickled; and the shiitake is slowly making its way into western cuisine as well. There is a global industry in shiitake production, with local farms in most western countries in addition to large scale importation from China, Japan, and elsewhere. Because they can now be grown world wide, their availability is widespread and their price has decreased. # Medicinal use Shiitake mushrooms have been researched for their medicinal benefits, most notably their anti-tumor properties in laboratory mice. These studies have also identified the polysaccharide lentinan, a (1-3) β-D-glucan, as the active compound responsible for the anti-tumor effects. Extracts from shiitake mushrooms have also been researched for many other immunological benefits, ranging from anti-viral properties to possible treatments for severe allergies, as well as arthritis. Lenthionine, a key flavour compound of shiitake, also inhibits platelet aggregation, so it is a promising treatment for thrombosis. Shiitake are also one of a few known natural sources of vegan and kosher vitamin D (vitamin D2). # References in popular culture Shiitake is often referred to in popular culture, usually for its spelling similarity to "shit." - In the 2002 film Austin Powers in Goldmember, a scene with a character speaking Japanese sees the sentence "Please eat some Shitake mushrooms" as a translation at the bottom of the screen. However, the "-ake mushrooms" portion is obscured temporarily so that it reads, "Please eat some Shit", implying the vernacular. Note that the correct spelling is "Shiitake"; without the modification the joke would not work. A similar joke appears in the movie Spy Kids. - In the short film The Madagascar Penguins in a Christmas Caper, from the movie Madagascar (2004), one of the penguins, Skipper, exclaims "Shiitake Mushrooms!", again implying the vernacular. - In the second series of The Catherine Tate Show, the fictional characters Janice and Ray, who frequently complain about restaurant meals, expressed disgust about being fed, what they described as "dried shit ache mushrooms". - In the Japanese anime series Cowboy Bebop, shiitake mushrooms are a central plot device in the episode "Mushroom Samba." - In the videogame Castlevania: Symphony of the Night, shiitake mushrooms can be found and eaten to restore the player's health. - In the videogame Chrono Trigger, the party encounters large, mobile, mushroom-like enemies called "Shitake" in the Prehistoric period of 65,000,000 B.C. - In the videogame Kingdom Hearts, if you bounce a Rare Truffle 50 times, you get a "Shiitake Rank" to signify that you have done so. - In the book Dragon Rider by Cornelia Funke, shiitake are one of the many types of mushrooms cultivated by brownies. - On the cooking competition television programme Iron Chef, shiitake mushrooms are a common ingredient in many of the entrées. - In the Japanese manga series Hajime no Ippo, Mamoru Takamura uses dried Shiitake as part of his weight management program in preparation for his World Championship title match. - In the Spike TV game show, MXC, a game called "Eat Shitake" is played in which the players must hold on to a large artificial mushroom while it spins across a body of water. If they make it across without slipping off, they score a point for their team. - In the movie Spy Kids, Carmen fixes her vulgar with the sentence " Oh shii..take mushrooms"	Shiitake Template:Mycomorphbox The shiitake (Lentinula edodes) is an edible mushroom native to East Asia. It is generally known in the English-speaking world by its Japanese name, shiitake Template:Audio (kanji: 椎茸; lit. "shii mushroom", from the Japanese name of the tree that provides the dead logs on which it is typically cultivated). In Chinese, it is called xiānggū (香菇, lit. "fragrant mushroom"). Two Chinese variant names for high grades of shiitake are dōnggū (Template:Zh-c, "winter mushroom") and huāgū (花菇, "flower mushroom", which has a flower-like cracking pattern on the mushroom's upper surface); both are produced at colder temperatures. Other names by which the mushroom is known in English include Chinese black mushroom and black forest mushroom. In Korean it is called pyogo (hangul: 표고; hanja: 瓢菰), in Thai they are called hed hom (เห็ดหอม, "fragrant mushroom"), and in Vietnamese they are called nấm hương ("fragrant mushroom"). The species was formerly known as Lentinus edodes and Agaricus edodes. The latter name was first applied by the English botanist Miles Joseph Berkeley in 1878. # History of cultivation Shiitake are native to China but have been grown in both Japan and China since prehistoric times[1]. They have been cultivated for over 1000 years; the first written record of shiitake cultivation can be traced to Wu Sang Kwuang, born during the Song Dynasty (960-1127 A.D.). However, some documents record the uncultivated mushroom being eaten as early as 199 A.D. During the Ming Dynasty (1368-1644 A.D.), physician Wu Juei wrote that the mushroom could be used not only as a food but was taken as a remedy for upper respiratory diseases, poor blood circulation, liver trouble, exhaustion and weakness, and to boost qi, or life energy. It was also believed to prevent premature aging. Before 1982 the Japanese variety of these mushooms could only be grown in traditional locations using ancient methods. In the late '70s, Gary F. Leatham published a doctoral thesis based on his research on the budding and growth of the Japan Islands variety; the work helped make commercial cultivation possible world-wide, and Dr. Leatham is now known in the industry as the "Father of Shiitake farming in the USA." # Culinary use Shiitake have many uses in Chinese and Japanese cuisines. They are served in miso soup, used as the basis for a kind of vegetarian dashi, and also as an ingredient in many steamed and simmered dishes. In Thailand, they can be fried as well as steamed. Shiitake are often dried and sold as preserved food in packages. These must be rehydrated by soaking in water before using. Many people prefer dried shiitake to fresh, considering that the sun-drying process draws out the superior umami flavour from the dried mushrooms by breaking down proteins into amino acids. The stems of shiitake are rarely used in Japanese and other cuisines, primarily because the stems are harder and take longer to cook than the soft fleshy caps. The highest grade of shiitake are called donko in Japanese. Today, Shiitake mushrooms have become popular in many other countries as well. Russia produces and also consumes large amounts of them, mostly sold pickled; and the shiitake is slowly making its way into western cuisine as well. There is a global industry in shiitake production, with local farms in most western countries in addition to large scale importation from China, Japan, and elsewhere. Because they can now be grown world wide, their availability is widespread and their price has decreased. # Medicinal use Shiitake mushrooms have been researched for their medicinal benefits, most notably their anti-tumor properties in laboratory mice. These studies have also identified the polysaccharide lentinan, a (1-3) β-D-glucan, as the active compound responsible for the anti-tumor effects.[2] Extracts from shiitake mushrooms have also been researched for many other immunological benefits, ranging from anti-viral properties to possible treatments for severe allergies, as well as arthritis.[3] Lenthionine, a key flavour compound of shiitake, also inhibits platelet aggregation, so it is a promising treatment for thrombosis.[citation needed] Shiitake are also one of a few known natural sources of vegan and kosher vitamin D (vitamin D2). # References in popular culture Template:Trivia Shiitake is often referred to in popular culture, usually for its spelling similarity to "shit." - In the 2002 film Austin Powers in Goldmember, a scene with a character speaking Japanese sees the sentence "Please eat some Shitake mushrooms" as a translation at the bottom of the screen. However, the "-ake mushrooms" portion is obscured temporarily so that it reads, "Please eat some Shit", implying the vernacular. Note that the correct spelling is "Shiitake"; without the modification the joke would not work. A similar joke appears in the movie Spy Kids. - In the short film The Madagascar Penguins in a Christmas Caper, from the movie Madagascar (2004), one of the penguins, Skipper, exclaims "Shiitake Mushrooms!", again implying the vernacular. - In the second series of The Catherine Tate Show, the fictional characters Janice and Ray, who frequently complain about restaurant meals, expressed disgust about being fed, what they described as "dried shit ache mushrooms". - In the Japanese anime series Cowboy Bebop, shiitake mushrooms are a central plot device in the episode "Mushroom Samba." - In the videogame Castlevania: Symphony of the Night, shiitake mushrooms can be found and eaten to restore the player's health. - In the videogame Chrono Trigger, the party encounters large, mobile, mushroom-like enemies called "Shitake" in the Prehistoric period of 65,000,000 B.C. - In the videogame Kingdom Hearts, if you bounce a Rare Truffle 50 times, you get a "Shiitake Rank" to signify that you have done so. - In the book Dragon Rider by Cornelia Funke, shiitake are one of the many types of mushrooms cultivated by brownies. - On the cooking competition television programme Iron Chef, shiitake mushrooms are a common ingredient in many of the entrées. - In the Japanese manga series Hajime no Ippo, Mamoru Takamura uses dried Shiitake as part of his weight management program in preparation for his World Championship title match. - In the Spike TV game show, MXC, a game called "Eat Shitake" is played in which the players must hold on to a large artificial mushroom while it spins across a body of water. If they make it across without slipping off, they score a point for their team. - In the movie Spy Kids, Carmen fixes her vulgar with the sentence " Oh shii..take mushrooms"	https://www.wikidoc.org/index.php/Lentinula_edodes
96b4c67f00a69125ff817ddee3aa2e93021df1d9	wikidoc	Lobotomy	Lobotomy # Overview A lobotomy (Greek: lobos: Lobe of brain, tomos: "cut/slice") is a form of psychosurgery, also known as a leukotomy or leucotomy (from Greek leukos: clear or white and tomos meaning "cut/slice"). It consists of cutting the connections to and from, or simply destroying, the prefrontal cortex. These procedures often result in major personality changes and possible mental retardation. Lobotomies were used in the past to treat a wide range of severe mental illnesses, including schizophrenia, clinical depression, and various anxiety disorders. # History In 1890, Dr. Gottlieb Burckhardt performed partial leucotomies on six patients of a psychiatric hospital in Switzerland. He drilled holes into their heads and extracted sections of their frontal lobes. One died after the operation, and another was found dead in a river 10 days after release (whether by accident, suicide, or crime is unknown). The others exhibited altered behavior. Based on his research about brain function, the Portuguese physician and neurologist António Egas Moniz in 1936 developed a technique for leucotomy in humans. His method involved drilling holes in patients' heads and destroying the tissue connecting the frontal lobes by injecting alcohol into them. Moniz won the Nobel Prize for medicine in 1949 for this work. It was intended to give relief to patients who were hopelessly ill and severely agitated. The procedure was refined by British psychiatrists including Eric Cunningham Dax. Drs. Walter Freeman and James W. Watts refined Moniz's procedure, brought the surgery to the US, and changed its name from leucotomy to lobotomy. Freeman later developed a simplified procedure to reach frontal lobe tissue through the tear ducts. In his trans-orbital lobotomy, he used a mallet to force a thin surgical instrument through the thin layer of skull at the top of the eye socket. The pick was then moved to sever connections between the frontal lobes and rest of the brain. Because of the appearance of the instrument, it was termed an "ice pick lobotomy." This technique could be performed in a doctor's office rather than in an operating room, and required only a few minutes to perform. Watts sharply disagreed with him over using this procedure and their partnership ended. Concerns about lobotomy steadily grew. Numerous countries, including Germany and Japan banned it, as did several U.S. states. Lobotomy was legally practiced in controlled and regulated U.S. centers and in Finland, Sweden, Norway (2005 cases), the United Kingdom, Spain, India, Belgium and the Netherlands. In 1977, the U.S. Congress created a National Committee for the Protection of Human Subjects of Biomedical and Behavioral Research to investigate allegations that psychosurgery — including lobotomy techniques — was used to control minorities and restrain individual rights. It also investigated after-effects of the surgery. The committee concluded that some extremely limited and properly performed psychosurgery could have positive effects. By the early 1970s the practice had generally ceased, but some countries continued small-scale operations through the late 1980s. In France, 32 lobotomies were performed between 1980 and 1986 according to an IGAS report; about 15 each year in the UK, 70 in Belgium, and about 15 for the Massachusetts General Hospital of Boston. # Scale Lobotomy procedures were done most frequently in the United States, where approximately 40,000 persons were so treated. Great Britain performed procedures on 17,000 people, and the three Scandinavian countries had a combined figure of approximately 9,300 persons treated. # Cases - Rosemary Kennedy, the sister of President John F. Kennedy, was given a lobotomy when her father complained to doctors about the 23-year-old’s moodiness. Dr. Walter Freeman personally performed the procedure. Rather than any improvement, however, the lobotomy reduced Rosemary to an infantile mentality including incontinence. Her verbal skills were reduced to unintelligible babble. Her father hid the nature of Rosemary's affliction for years and described it as the result of mental retardation. Rosemary's sister Eunice Kennedy Shriver founded the Special Olympics in her honor in 1968. - Howard Dully had a lobotomy at 12, after his stepmother was simply tired of his "youthful defiance". At the age of 56 he said, "I've always felt different -- wondered if something's missing from my soul. I have no memory of the operation". Late in his life, Dully uncovered the story of his lobotomy. Crown Publishers published Howard Dully's memoir (co-written by Charles Fleming), My Lobotomy , in September 2007. - New Zealand author and poet, Janet Frame was due to have a lobotomy because of a diagnosis of mental illness. She was saved from this procedure by receiving a literary award the day before her operation was to take place. # In popular culture - Transorbital lobotomy is discussed in a scene from the 2001 horror movie, Session 9. The post-operative treatment is described as "a pair of sunglasses". Later, a character is seen lobotomized in such a fashion, walking around in sunglasses. - The Simpsons episodes 7F24 Stark Raving Dad where Bart daydreams of his father undergoing the operation and 2F03 Treehouse of Horror V where Ned Flanders performs lobotomies on the Simpson family. - The Velvet Underground song, "Lady Godiva's Operation", depicts a lobotomy. - A lobotomy is mentioned in the song "Paralyzed" by KISS off of their album Revenge. "Don't see nothin' in my eyes, 'cause man I've been lobotomized" - A lobotomy is mentioned in the song "Leper Friend" by Dog Fashion Disco from their album "The Embryo's in Bloom". "The cure for clinical depression is a lobotomy." - In the 1947 radio play "Dark Curtain", Veronica Lake portrays a paranoid schizophrenic bride-to-be who receives a failed series of convulsive electroshock treatments followed by a successful lobotomy. The shock treatments and the brain surgery are described in clinical detail. The glowingly positive light in which these "advances in modern medicine" were depicted make it difficult for a contemporary audience to listen to it. - In Tennessee Williams's play, Suddenly, Last Summer, Catherine, the protagonist, is threatened with a lobotomy to stop her from telling the truth about her cousin Sebastian. - In the Pink Floyd song Brain Damage, the second verse includes the lines "You raise the blade/You make the change/You rearrange me till I'm sane", discussing lobotomy. - In the 1962 book One Flew Over the Cuckoo's Nest (and the 1975 film based on it), McMurphy was lobotomized after he angrily attacked Nurse Ratched. - The novel All the King's Men by Robert Penn Warren described a lobotomy. - In the 1968 film Planet of the Apes, Taylor was separated from his fellow astronauts. He later finds that the apes gave astronaut Landon a lobotomy. - The 1982 biopic Frances included a fictional scene of the titular actress Frances Farmer undergoing transorbital lobotomy. - In the DCAU Justice League two part episode, "A Better World", Justice Lord Superman uses his heat-ray ability to lobotomize his most powerful enemy, Doomsday, defeating him. - The Ramones song titled "Teenage Lobotomy" as well as the book "Lobotomy: Surviving the Ramones" written by Dee Dee Ramone. - The Iron Maiden album "Piece Of Mind" depicts the character Eddie after having a lobotomy. Therefore they have taken a piece of Eddie's mind. - The track "Lobotomy Gets 'em Home" by The Men They Couldn't Hang, is about the enforced treatment of the American actress Frances Farmer - Karen from the US localization of "The Office" sarcastically mentions giving herself a lobotomy with a corkscrew after a difficult day at work. - British rock band "Bullamakanka" have a song called "lobotomy" about a boy with suicidal tendencies. - Zebrahead has a song entitled "Lobotomy for Dummies", which is about a man who's girlfriend broke up with him, and wishes to undergo lobotomy so he doesn't have to deal with it. - Sylvia Plath's novel "The Bell Jar" mentions a young woman Valerie, whom Plath met in the mental institution, who was lobotomized. - In the Playstation 2 video game Timesplitters Future Perfect, the announcer may exclaim "Lobotomy!" if a headshot is performed in arcade mode. - In the 1996 X-Files episode entitled "Unruhe", the villain performs trans-orbital lobotomies on his victims.	Lobotomy # Overview A lobotomy (Greek: lobos: Lobe of brain, tomos: "cut/slice") is a form of psychosurgery, also known as a leukotomy or leucotomy (from Greek leukos: clear or white and tomos meaning "cut/slice"). It consists of cutting the connections to and from, or simply destroying, the prefrontal cortex. These procedures often result in major personality changes and possible mental retardation. Lobotomies were used in the past to treat a wide range of severe mental illnesses, including schizophrenia, clinical depression, and various anxiety disorders. # History In 1890, Dr. Gottlieb Burckhardt performed partial leucotomies on six patients of a psychiatric hospital in Switzerland. He drilled holes into their heads and extracted sections of their frontal lobes. One died after the operation, and another was found dead in a river 10 days after release (whether by accident, suicide, or crime is unknown). The others exhibited altered behavior. Based on his research about brain function, the Portuguese physician and neurologist António Egas Moniz in 1936 developed a technique for leucotomy in humans. His method involved drilling holes in patients' heads and destroying the tissue connecting the frontal lobes by injecting alcohol into them. Moniz won the Nobel Prize for medicine in 1949 for this work. It was intended to give relief to patients who were hopelessly ill and severely agitated. The procedure was refined by British psychiatrists including Eric Cunningham Dax. Drs. Walter Freeman and James W. Watts refined Moniz's procedure, brought the surgery to the US, and changed its name from leucotomy to lobotomy. Freeman later developed a simplified procedure to reach frontal lobe tissue through the tear ducts. In his trans-orbital lobotomy, he used a mallet to force a thin surgical instrument through the thin layer of skull at the top of the eye socket. The pick was then moved to sever connections between the frontal lobes and rest of the brain. Because of the appearance of the instrument, it was termed an "ice pick lobotomy." This technique could be performed in a doctor's office rather than in an operating room, and required only a few minutes to perform. Watts sharply disagreed with him over using this procedure and their partnership ended. Concerns about lobotomy steadily grew. Numerous countries, including Germany and Japan banned it, as did several U.S. states. Lobotomy was legally practiced in controlled and regulated U.S. centers and in Finland, Sweden, Norway (2005 cases[1]), the United Kingdom, Spain, India, Belgium and the Netherlands. In 1977, the U.S. Congress created a National Committee for the Protection of Human Subjects of Biomedical and Behavioral Research to investigate allegations that psychosurgery — including lobotomy techniques — was used to control minorities and restrain individual rights. It also investigated after-effects of the surgery. The committee concluded that some extremely limited and properly performed psychosurgery could have positive effects. By the early 1970s the practice had generally ceased, but some countries continued small-scale operations through the late 1980s. In France, 32 lobotomies were performed between 1980 and 1986 according to an IGAS report; about 15 each year in the UK, 70 in Belgium, and about 15 for the Massachusetts General Hospital of Boston.[2] # Scale Lobotomy procedures were done most frequently in the United States, where approximately 40,000 persons were so treated. Great Britain performed procedures on 17,000 people, and the three Scandinavian countries had a combined figure of approximately 9,300 persons treated.[3] # Cases - Rosemary Kennedy, the sister of President John F. Kennedy, was given a lobotomy when her father complained to doctors about the 23-year-old’s moodiness. Dr. Walter Freeman personally performed the procedure. Rather than any improvement, however, the lobotomy reduced Rosemary to an infantile mentality including incontinence. Her verbal skills were reduced to unintelligible babble. Her father hid the nature of Rosemary's affliction for years and described it as the result of mental retardation. Rosemary's sister Eunice Kennedy Shriver founded the Special Olympics in her honor in 1968. - Howard Dully had a lobotomy at 12, after his stepmother was simply tired of his "youthful defiance". At the age of 56 he said, "I've always felt different -- wondered if something's missing from my soul. I have no memory of the operation". Late in his life, Dully uncovered the story of his lobotomy. Crown Publishers published Howard Dully's memoir (co-written by Charles Fleming), My Lobotomy [1], in September 2007.[4][5] - New Zealand author and poet, Janet Frame was due to have a lobotomy because of a diagnosis of mental illness. She was saved from this procedure by receiving a literary award the day before her operation was to take place. # In popular culture - Transorbital lobotomy is discussed in a scene from the 2001 horror movie, Session 9. The post-operative treatment is described as "a pair of sunglasses". Later, a character is seen lobotomized in such a fashion, walking around in sunglasses. - The Simpsons episodes 7F24 Stark Raving Dad where Bart daydreams of his father undergoing the operation and 2F03 Treehouse of Horror V where Ned Flanders performs lobotomies on the Simpson family. - The Velvet Underground song, "Lady Godiva's Operation", depicts a lobotomy. - A lobotomy is mentioned in the song "Paralyzed" by KISS off of their album Revenge. "Don't see nothin' in my eyes, 'cause man I've been lobotomized" - A lobotomy is mentioned in the song "Leper Friend" by Dog Fashion Disco from their album "The Embryo's in Bloom". "The cure for clinical depression is a lobotomy." - In the 1947 radio play "Dark Curtain", Veronica Lake portrays a paranoid schizophrenic bride-to-be who receives a failed series of convulsive electroshock treatments followed by a successful lobotomy. The shock treatments and the brain surgery are described in clinical detail. The glowingly positive light in which these "advances in modern medicine" were depicted make it difficult for a contemporary audience to listen to it. - In Tennessee Williams's play, Suddenly, Last Summer, Catherine, the protagonist, is threatened with a lobotomy to stop her from telling the truth about her cousin Sebastian. - In the Pink Floyd song Brain Damage, the second verse includes the lines "You raise the blade/You make the change/You rearrange me till I'm sane", discussing lobotomy. - In the 1962 book One Flew Over the Cuckoo's Nest (and the 1975 film based on it), McMurphy was lobotomized after he angrily attacked Nurse Ratched. - The novel All the King's Men by Robert Penn Warren described a lobotomy. - In the 1968 film Planet of the Apes, Taylor was separated from his fellow astronauts. He later finds that the apes gave astronaut Landon a lobotomy. - The 1982 biopic Frances included a fictional scene of the titular actress Frances Farmer undergoing transorbital lobotomy. - In the DCAU Justice League two part episode, "A Better World", Justice Lord Superman uses his heat-ray ability to lobotomize his most powerful enemy, Doomsday, defeating him. - The Ramones song titled "Teenage Lobotomy" as well as the book "Lobotomy: Surviving the Ramones" written by Dee Dee Ramone. - The Iron Maiden album "Piece Of Mind" depicts the character Eddie after having a lobotomy. Therefore they have taken a piece of Eddie's mind. - The track "Lobotomy Gets 'em Home" by The Men They Couldn't Hang, is about the enforced treatment of the American actress Frances Farmer - Karen from the US localization of "The Office" sarcastically mentions giving herself a lobotomy with a corkscrew after a difficult day at work. - British rock band "Bullamakanka" have a song called "lobotomy" about a boy with suicidal tendencies. - Zebrahead has a song entitled "Lobotomy for Dummies", which is about a man who's girlfriend broke up with him, and wishes to undergo lobotomy so he doesn't have to deal with it. - Sylvia Plath's novel "The Bell Jar" mentions a young woman Valerie, whom Plath met in the mental institution, who was lobotomized. - In the Playstation 2 video game Timesplitters Future Perfect, the announcer may exclaim "Lobotomy!" if a headshot is performed in arcade mode. - In the 1996 X-Files episode entitled "Unruhe", the villain performs trans-orbital lobotomies on his victims.	https://www.wikidoc.org/index.php/Leukotomy
fce7d4e812b7819e795357e440fdbb4b7c084852	wikidoc	Licorice	Licorice Liquorice or licorice (see spelling differences) (Template:IPAEng, or Template:IPA) is the root of Glycyrrhiza glabra, from which a sweet flavour can be extracted. The liquorice plant is a legume (related to beans and peas) and native to southern Europe and parts of Asia. It is an herbaceous perennial, growing to 1 m in height, with pinnate leaves about 7–15 centimetres (3–6 inches) long, with 9–17 leaflets. The flowers are 0.8–1.2 cm (1/3 to 1/2 inch) long, purple to pale whitish blue, produced in a loose inflorescence. The fruit is an oblong pod, 2–3 centimetres (about 1 inch) long, containing several seeds. # Cultivation and uses Liquorice grows best in deep, fertile, well-drained soils, with full sun, and is harvested in the autumn two to three years after planting. Liquorice extract is produced by boiling liquorice root and subsequently evaporating most of the water (in fact, the word 'liquorice' is derived from the Ancient Greek words for 'sweet root'). Liquorice extract is traded both in solid and syrup form. Its active principle is glycyrrhizin, a sweetener more than 50 times as sweet as sucrose which also has pharmaceutical effects. G. uralensis contains this chemical in much greater concentration. ## Culinary use Liquorice flavour is found in a wide variety of liquorice candies. The most popular in the United Kingdom are liquorice allsorts. In continental Europe, however, far stronger, saltier candies are preferred. It should be noted, though, that in most of these candies the taste is reinforced by aniseed oil, and the actual content of liquorice is quite low. Pontefract in Yorkshire was the first place where liquorice mixed with sugar began to be used as a sweet in the same way it is in the modern day. In the Netherlands Liquorice candy is called "Drop" (and it is actually one of the most popular forms of candy), but only a few of the many forms that are sold contain aniseed, although mixing it with mint, menthol or with laurel is popular, and mixing it with Ammonium chloride creates the very popular salty liquorice. Liquorice is also found in some soft drinks (such as root beer), and is in some herbal teas where it provides a sweet aftertaste. The flavour is common in medicines to disguise unpleasant flavours. Dutch youth often make their own "Dropwater" (Liquorice water) by putting a few pieces of laurel liquorice and a piece of liquorice root in a bottle with water and then shake it to a frothy liquid, and Dutch youths like to drink a liquorice based liqueur called a "dropshot". Liquorice is popular in Italy (particularly in the South) and Spain in its natural form. The root of the plant is simply dug up, washed and chewed as mouth-freshener. Throughout Italy unsweetened liquorice is consumed in the form of small black pieces made only from 100% pure liquorice extract; the taste is bitter and intense. In Calabria a popular liqueur is made from pure liquorice extract. Liquorice is also very popular in Syria where it is sold as a drink. Dried liquorice root can be chewed as a sweet. According to the US Department of Agriculture Food Database, black liquorice contains approximately 100 calories per ounce (28g). Chinese cuisine uses liquorice as a culinary spice for savoury foods. It is often employed to flavour broths and foods simmered in soy sauce. Other herbs and spices of similar flavour include anise, star anise, tarragon, and fennel. It is also the main ingredient of a very well known soft drink in Egypt, called عرقسوس ('erk-soos) ## Medicinal use Powdered liquorice root is an effective expectorant, and has been used for this purpose since ancient times, especially in Ayurvedic medicine where it is also used in tooth powders. Modern cough syrups often include liquorice extract as an ingredient. Additionally, liquorice may be useful in conventional and naturopathic medicine for both mouth ulcers and peptic ulcers. Non-prescription aphthous ulcer treatment CankerMelts incorporates glycyrrhiza in a dissolving adherent troche. Liquorice is also a mild laxative and may be used as a topical antiviral agent for shingles, ophthalmic, oral or genital herpes. Liquorice affects the body's endocrine system as it contains isoflavones (phytoestrogens). It can lower the amount of serum testosterone, but whether it affects the amount of free testosterone is unclear. Large doses of glycyrrhizinic acid and glycyrrhetinic acid in liquorice extract can lead to hypokalemia and serious increases in blood pressure, a syndrome known as apparent mineralocorticoid excess. These side effects stem from the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase (type 2) and subsequent increase in activity of cortisol on the kidney. 11β-hydroxysteroid dehydrogenase normally inactivates cortisol in the kidney; thus, liquorice's inhibition of this enzyme makes the concentration of cortisol appear to increase. Cortisol acts at the same receptor as the hormone aldosterone in the kidney and the effects mimic aldosterone excess, although aldosterone remains low or normal during liquorice overdose. To decrease the chances of these serious side effects, deglycyrrhizinated liquorice preparations are available. The disabling of similar enzymes in the gut by glycyrrhizinic acid and glycyrrhetinic acid also causes increased mucus and decreased acid secretion. It inhibits Helicobacter pylori, is used as an aid for healing stomach and duodenal ulcers, and in moderate amounts may soothe an upset stomach. Liquorice can be used to treat ileitis, leaky gut syndrome, irritable bowel syndrome and Crohn's disease as it is antispasmodic in the bowels. Liquorice is an adaptogen which helps reregulate the Hypothalamic-pituitary-adrenal axis. It can also be used for auto-immune conditions including lupus, scleroderma, rheumatoid arthritis and animal dander allergies. In traditional Chinese medicine, liquorice is commonly used in herbal formulae to "harmonize" the other ingredients in the formula and to carry the formula into all 12 of the regular meridians and to relieve a spasmodic cough. In traditional American herbalism it is used in the Hoxsey anti-cancer formula. ## Toxicity Excessive consumption of liquorice or liquorice candy is known to be toxic to the liver and may produce hypokalemia, hypertension and edema. There have been occasional cases where blood pressure has increased with excessive consumption of liquorice tea, but such occasions are rare and reversible when the herb is withdrawn. Most cases of hypertension from liquorice were caused by eating too much concentrated liquorice candy. Doses as low as 50g daily for two weeks can cause a significant rise in blood pressure. # Gallery - Sliver of liquorice root Sliver of liquorice root - Various liqourice root slivers Various liqourice root slivers # Notes - ↑ Jump up to: 1.0 1.1 1.2 "Glycyrrhiza glabra information from NPGS/GRIN". www.ars-grin.gov. Retrieved 2008-03-06..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} - ↑ Jump up to: 2.0 2.1 Huxley, A., ed. (1992). New RHS Dictionary of Gardening. ISBN 0-333-47494-5 - ↑ "Right good food from the Ridings". AboutFood.com. 25 October 2007. Check date values in: \|date= (help) - ↑ Dutch website of Wageningen University with English information about "Drop" - ↑ semi-official "drop-shot" site (In Dutch) - ↑ Licorice Calories - ↑ عرقسوس (Liquorice) - ↑ Das, S.K. "Deglycyrrhizinated liquorice in aphthous ulcers". The Journal of the Association of Physicians of India. Association of Physicians of India. 37 (10): 647. Unknown parameter \|coauthors= ignored (help) - ↑ Krausse, R. (2004). "In vitro anti-Helicobacter pylori activity of Extractum liquiritiae, glycyrrhizin and its metabolites". The Journal of Antimicrobial Chemotherapy. Oxford University Press. 54 (1): 243–246. Unknown parameter \|coauthors= ignored (help) - ↑ Materia Medica, retrieved 24 May 2007 - ↑ Jump up to: 11.0 11.1 Winston, David (2007). Adaptogens: Herbs for Strength, Stamina, and Stress Relief. Healing Arts Press. Unknown parameter \|coauthors= ignored (help) - ↑ Bensky, Dan (2004). Chinese Herbal Medicine: Materia Medica, Third Edition. Eastland Press. ISBN 0939616424. Unknown parameter \|coauthors= ignored (help) - ↑ The Nurse's Guide To Herbal Remedies from Salisbury University - ↑ Liquorice and hypertension Editorial in The Netherlands Journal of Medicine, 2005 - ↑ A Guide to Medicinal and Aromatic Plants from Purdue University - ↑ Subhuti Dharmananda, Ph.D., Safety Issues Affecting Herbs: Herbs that May Increase Blood Pressue, retrieved 24 May 2007 - ↑ Sigurjónsdóttir, H.A., et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. Journal of Human Hypertension (2001) 15, 549-552.	Licorice Liquorice or licorice (see spelling differences) (Template:IPAEng, or Template:IPA) is the root of Glycyrrhiza glabra, from which a sweet flavour can be extracted. The liquorice plant is a legume (related to beans and peas) and native to southern Europe and parts of Asia. It is an herbaceous perennial, growing to 1 m in height, with pinnate leaves about 7–15 centimetres (3–6 inches) long, with 9–17 leaflets. The flowers are 0.8–1.2 cm (1/3 to 1/2 inch) long, purple to pale whitish blue, produced in a loose inflorescence. The fruit is an oblong pod, 2–3 centimetres (about 1 inch) long, containing several seeds.[2] # Cultivation and uses Liquorice grows best in deep, fertile, well-drained soils, with full sun, and is harvested in the autumn two to three years after planting.[2] Liquorice extract is produced by boiling liquorice root and subsequently evaporating most of the water (in fact, the word 'liquorice' is derived from the Ancient Greek words for 'sweet root'). Liquorice extract is traded both in solid and syrup form. Its active principle is glycyrrhizin, a sweetener more than 50 times as sweet as sucrose which also has pharmaceutical effects. G. uralensis contains this chemical in much greater concentration. ## Culinary use Template:Mainarticle Liquorice flavour is found in a wide variety of liquorice candies. The most popular in the United Kingdom are liquorice allsorts. In continental Europe, however, far stronger, saltier candies are preferred. It should be noted, though, that in most of these candies the taste is reinforced by aniseed oil, and the actual content of liquorice is quite low. Pontefract in Yorkshire was the first place where liquorice mixed with sugar began to be used as a sweet in the same way it is in the modern day.[3] In the Netherlands Liquorice candy is called "Drop" (and it is actually one of the most popular forms of candy), but only a few of the many forms that are sold contain aniseed, although mixing it with mint, menthol or with laurel is popular, and mixing it with Ammonium chloride creates the very popular salty liquorice. [4] Liquorice is also found in some soft drinks (such as root beer), and is in some herbal teas where it provides a sweet aftertaste. The flavour is common in medicines to disguise unpleasant flavours. Dutch youth often make their own "Dropwater" (Liquorice water) by putting a few pieces of laurel liquorice and a piece of liquorice root in a bottle with water and then shake it to a frothy liquid, and Dutch youths like to drink a liquorice based liqueur called a "dropshot".[5] Liquorice is popular in Italy (particularly in the South) and Spain in its natural form. The root of the plant is simply dug up, washed and chewed as mouth-freshener. Throughout Italy unsweetened liquorice is consumed in the form of small black pieces made only from 100% pure liquorice extract; the taste is bitter and intense. In Calabria a popular liqueur is made from pure liquorice extract. Liquorice is also very popular in Syria where it is sold as a drink. Dried liquorice root can be chewed as a sweet. According to the US Department of Agriculture Food Database, black liquorice contains approximately 100 calories per ounce (28g).[6] Chinese cuisine uses liquorice as a culinary spice for savoury foods. It is often employed to flavour broths and foods simmered in soy sauce. Other herbs and spices of similar flavour include anise, star anise, tarragon, and fennel. It is also the main ingredient of a very well known soft drink in Egypt, called عرقسوس ('erk-soos) [7] ## Medicinal use Powdered liquorice root is an effective expectorant, and has been used for this purpose since ancient times, especially in Ayurvedic medicine where it is also used in tooth powders. Modern cough syrups often include liquorice extract as an ingredient. Additionally, liquorice may be useful in conventional and naturopathic medicine for both mouth ulcers[8] and peptic ulcers.[9] Non-prescription aphthous ulcer treatment CankerMelts incorporates glycyrrhiza in a dissolving adherent troche. Liquorice is also a mild laxative and may be used as a topical antiviral agent for shingles, ophthalmic, oral or genital herpes. Liquorice affects the body's endocrine system as it contains isoflavones (phytoestrogens). It can lower the amount of serum testosterone,[10] but whether it affects the amount of free testosterone is unclear. Large doses of glycyrrhizinic acid and glycyrrhetinic acid in liquorice extract can lead to hypokalemia and serious increases in blood pressure, a syndrome known as apparent mineralocorticoid excess. These side effects stem from the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase (type 2) and subsequent increase in activity of cortisol on the kidney. 11β-hydroxysteroid dehydrogenase normally inactivates cortisol in the kidney; thus, liquorice's inhibition of this enzyme makes the concentration of cortisol appear to increase. Cortisol acts at the same receptor as the hormone aldosterone in the kidney and the effects mimic aldosterone excess, although aldosterone remains low or normal during liquorice overdose. To decrease the chances of these serious side effects, deglycyrrhizinated liquorice preparations are available. The disabling of similar enzymes in the gut by glycyrrhizinic acid and glycyrrhetinic acid also causes increased mucus and decreased acid secretion. It inhibits Helicobacter pylori, is used as an aid for healing stomach and duodenal ulcers, and in moderate amounts may soothe an upset stomach. Liquorice can be used to treat ileitis, leaky gut syndrome, irritable bowel syndrome and Crohn's disease as it is antispasmodic in the bowels.[11] Liquorice is an adaptogen which helps reregulate the Hypothalamic-pituitary-adrenal axis. It can also be used for auto-immune conditions including lupus, scleroderma, rheumatoid arthritis and animal dander allergies.[11] In traditional Chinese medicine, liquorice is commonly used in herbal formulae to "harmonize" the other ingredients in the formula and to carry the formula into all 12 of the regular meridians[12] and to relieve a spasmodic cough. In traditional American herbalism it is used in the Hoxsey anti-cancer formula. ## Toxicity Excessive consumption of liquorice or liquorice candy is known to be toxic to the liver[13] and may produce hypokalemia, hypertension [14] and edema.[15] There have been occasional cases where blood pressure has increased with excessive consumption of liquorice tea, but such occasions are rare and reversible when the herb is withdrawn.[16] Most cases of hypertension from liquorice were caused by eating too much concentrated liquorice candy. Doses as low as 50g daily for two weeks can cause a significant rise in blood pressure.[17] # Gallery - Sliver of liquorice root Sliver of liquorice root - Various liqourice root slivers Various liqourice root slivers # Notes - ↑ Jump up to: 1.0 1.1 1.2 "Glycyrrhiza glabra information from NPGS/GRIN". www.ars-grin.gov. Retrieved 2008-03-06..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} - ↑ Jump up to: 2.0 2.1 Huxley, A., ed. (1992). New RHS Dictionary of Gardening. ISBN 0-333-47494-5 - ↑ "Right good food from the Ridings". AboutFood.com. 25 October 2007. Check date values in: \|date= (help) - ↑ [1] Dutch website of Wageningen University with English information about "Drop" - ↑ [2] semi-official "drop-shot" site (In Dutch) - ↑ Licorice Calories - ↑ عرقسوس (Liquorice) - ↑ Das, S.K. "Deglycyrrhizinated liquorice in aphthous ulcers". The Journal of the Association of Physicians of India. Association of Physicians of India. 37 (10): 647. Unknown parameter \|coauthors= ignored (help) - ↑ Krausse, R. (2004). "In vitro anti-Helicobacter pylori activity of Extractum liquiritiae, glycyrrhizin and its metabolites". The Journal of Antimicrobial Chemotherapy. Oxford University Press. 54 (1): 243–246. Unknown parameter \|coauthors= ignored (help) - ↑ Materia Medica, retrieved 24 May 2007 - ↑ Jump up to: 11.0 11.1 Winston, David (2007). Adaptogens: Herbs for Strength, Stamina, and Stress Relief. Healing Arts Press. Unknown parameter \|coauthors= ignored (help) - ↑ Bensky, Dan (2004). Chinese Herbal Medicine: Materia Medica, Third Edition. Eastland Press. ISBN 0939616424. Unknown parameter \|coauthors= ignored (help) - ↑ The Nurse's Guide To Herbal Remedies from Salisbury University - ↑ Liquorice and hypertension Editorial in The Netherlands Journal of Medicine, 2005 - ↑ A Guide to Medicinal and Aromatic Plants from Purdue University - ↑ Subhuti Dharmananda, Ph.D., Safety Issues Affecting Herbs: Herbs that May Increase Blood Pressue, retrieved 24 May 2007 - ↑ Sigurjónsdóttir, H.A., et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. Journal of Human Hypertension (2001) 15, 549-552. # External links - Herb Teas and Old Remedies : Liquorice (fr.with translator) - National Institute of Health - Medline - PDRhealth.com - Profile of Deglycyrrhizinated Licorice (DGL) - Chemical & Engineering News article on Licorice - Non-profit dedicated to promoting licorice - Offers information and more than 160 licorice products from 13 countries - Pontefract Liquorice Festival Template:Herbs & spices ar:عرقسوس bg:Женско биле cs:Lékořice lysá da:Glat Lakrids de:Lakritze hsb:Słódnik id:Licorice it:Glycyrrhiza glabra lb:Séissholz lt:Paprastasis saldymedis hu:Édesgyökér ms:Pokok Akar Manis nl:Zoethout no:Lakrisplante sr:Сладић fi:Lakritsikasvi sv:Lakritsrot th:ชะเอมเทศ vec:Glycyrrhiza glabra Template:WH Template:WS	https://www.wikidoc.org/index.php/Licorice
42b080ebbff47a0a1f8713fb38f95436948d11b2	wikidoc	Organism	Organism In biology and ecology, an organism (in Greek organon = instrument) is an individual living system (such as animal, plant, fungus or micro-organism). In at least some form, all organisms are capable of reacting to stimuli, reproduction, growth and maintenance as a stable whole (after FAO). An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs. Based on cell type, organisms may be divided into the prokaryotic and eukaryotic groups. The prokaryotes are generally considered to represent two separate domains, called the Bacteria and Archaea, which are not closer to one another than to the eukaryotes. The gap between prokaryotes and eukaryotes is widely considered a major missing link in evolutionary history. Eukaryotic organisms, with a membrane-bounded cell nucleus, also contain organelles, namely mitochondria and (in plants) plastids, generally considered to be derived from endosymbiotic bacteria. A similar symbiogenesis hypothesis has been proposed involving the origins of the cell nucleus, it is described as viral eukaryogenesis. Fungi, animals and plants are examples of species that are eukaryotes.More recently a clade, Neomura, has been proposed, by Thomas Cavalier-Smith, which groups together the Archaea and Eukarya. Cavalier-Smith also proposed that the Neomura evolved from Bacteria, more precisely from Actinobacteria. The phrase complex organism describes any organism with more than one cell. # Semantics The word "organism" may broadly be defined as an assembly of molecules that influence each other in such a way that they function as a more or less stable whole and have properties of life. However, many sources, lexical and scientific, add conditions that are problematic to defining the word. The Oxford English Dictionary defines an organism as " individual animal, plant, or single-celled life form" This definition problematically excludes non-animal and plant multi-cellular life forms such as some fungi and protista. Less controversially, perhaps, it excludes viruses and theoretically-possible man-made non-organic life forms. Chambers Online Reference provides a much broader definition: "any living structure, such as a plant, animal, fungus or bacterium, capable of growth and reproduction". The definition emphasises life; it allows for any life form, organic or otherwise, to be considered an organism. This does encompass all cellular life, as well as possible synthetic life. This definition does lack anything approximating to the word "individual" which would exclude viruses. Some may use a definition not including cells. For example its definition might be; a structure that has a DNA. This allows different things by definition to be counted as an organism. The word "organism" usually describes an independent collections of systems (for example circulatory, digestive, or reproductive) themselves collections of organs; these are, in turn, collections of tissues, which are themselves made of cells. ## Viruses Viruses are not typically considered to be organisms because they are incapable of "independent" reproduction or metabolism. This controversy is problematic, though, since some parasites and endosymbionts are also incapable of independent life. Although viruses have enzymes and molecules characteristic of living organisms, they are incapable of reproducing outside a host cell and most of their metabolic processes require a host and its 'genetic machinery.' ## Superorganism A superorganism is an organism consisting of many organisms. This is usually meant to be a social unit of eusocial animals, where division of labour is highly specialised and where individuals are not able to survive by themselves for extended periods of time. Ants are the most well known example of such a superorganism. Thermoregulation, a feature usually exhibited by individual organisms, does not occur in individuals or small groups of honeybees of the species Apis mellifera. When these bees pack together in clusters of between 5000 and 40000, the colony can thermoregulate. James Lovelock, with his "Gaia Theory" has paralleled the work of Vladimir Vernadsky, who suggested the whole of the biosphere in some respects can be considered as a superorganism. The concept of superorganism is under dispute, as many biologists maintain that in order for a social unit to be considered an organism by itself, the individuals should be in permanent physical connection to each other, and its evolution should be governed by selection to the whole society instead of individuals. While it's generally accepted that the society of eusocial animals is a unit of natural selection to at least some extent, most evolutionists claim that the individuals are still the primary units of selection. The question remains "What is to be considered the individual?". Darwinians like Richard Dawkins suggest that the individual selected is the "Selfish Gene". Others believe it is the whole genome of an organism. E.O. Wilson has shown that with ant-colonies and other social insects it is the breeding entity of the colony that is selected, and not its individual members. This could apply to the bacterial members of a stromatolite, which, because of genetic sharing, in some way comprise a single gene pool. Gaian theorists like Lynn Margulis would argue this applies equally to the symbiogenesis of the bacterial underpinnings of the whole of the Earth. It would appear, from computer simulations like Daisyworld that biological selection occurs at multiple levels simultaneously. It is also argued that humans are actually a superorganism that includes microorganisms such as bacteria. It is estimated that "the human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-D-erythritol 4-phosphate pathway–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes." . # Organizational terminology All organisms are classified by the science of alpha taxonomy into either taxa or clades. Taxa are ranked groups of organisms which run from the general (domain) to the specific (species). A broad scheme of ranks in hierarchical order is: - Domain - Kingdom - Phylum - Class - Order - Family - Genus - Species To give an example, Homo sapiens is the Latin binomial equating to modern humans. All members of the species sapiens are, at least in theory, genetically able to interbreed. Several species may belong to a genus, but the members of different species within a genus are unable to interbreed to produce fertile offspring. Homo, however, only has one surviving species (sapiens); Homo erectus, Homo neanderthalensis, &c. having become extinct thousands of years ago. Several genera belong to the same family and so on up the hierarchy. Eventually, the relevant kingdom (Animalia, in the case of humans) is placed into one of the three domains depending upon certain genetic and structural characteristics. All living organisms known to science are given classification by this system such that the species within a particular family are more closely related and genetically similar than the species within a particular phylum. # Chemistry Organisms are complex chemical systems, organized in ways that promote reproduction and some measure of sustainability or survival. The molecular phenomena of chemistry are fundamental in understanding organisms, but it is a philosophical error (reductionism) to reduce organismal biology to mere chemistry. It is generally the phenomena of entire organisms that determine their fitness to an environment and therefore the survivability of their DNA based genes. Organisms clearly owe their origin, metabolism, and many other internal functions to chemical phenomena, especially the chemistry of large organic molecules. Organisms are complex systems of chemical compounds which, through interaction with each other and the environment, play a wide variety of roles. Organisms are semi-closed chemical systems. Although they are individual units of life (as the definition requires) they are not closed to the environment around them. To operate they constantly take in and release energy. Autotrophs produce usable energy (in the form of organic compounds) using light from the sun or inorganic compounds while heterotrophs take in organic compounds from the environment. The primary chemical element in these compounds is carbon. The physical properties of this element such as its great affinity for bonding with other small atoms, including other carbon atoms, and its small size makes it capable of forming multiple bonds, make it ideal as the basis of organic life. It is able to form small compounds containing three atoms (such as carbon dioxide) as well as large chains of many thousands of atoms which are able to store data (nucleic acids), hold cells together and transmit information (protein). ## Macromolecules The compounds which make up organisms may be divided into macromolecules and other, smaller molecules. The four groups of macromolecule are nucleic acids, proteins, carbohydrates and lipids. Nucleic acids (specifically deoxyribonucleic acid, or DNA) store genetic data as a sequence of nucleotides. The particular sequence of the four different types of nucleotides (adenine, cytosine, guanine, and thymine) dictate the many characteristics which constitute the organism. The sequence is divided up into codons, each of which is a particular sequence of three nucleotides and corresponds to a particular amino acid. Thus a sequence of DNA codes for a particular protein which, due to the chemical properties of the amino acids of which it is made, folds in a particular manner and so performs a particular function. The following functions of protein have been recognized: - Enzymes, which catalyze all of the reactions of metabolism; - Structural proteins, such as tubulin, or collagen; - Regulatory proteins, such as transcription factors or cyclins that regulate the cell cycle; - Signalling molecules or their receptors such as some hormones and their receptors; - Defensive proteins, which can include everything from antibodies of the immune system, to toxins (e.g., dendrotoxins of snakes), to proteins that include unusual amino acids like canavanine. Lipids make up the membrane of cells which constitutes a barrier, containing everything within the cell and preventing compounds from freely passing into, and out of, the cell. In some multi-cellular organisms they serve to store energy and mediate communication between cells. Carbohydrates also store and transport energy in some organisms, but are more easily broken down than lipids. # Structure All organisms consist of monomeric units called cells; some contain a single cell (unicellular) and others contain many units (multicellular). Multicellular organisms are able to specialise cells to perform specific functions, a group of such cells is tissue the four basic types of which are epithelium, nervous tissue, muscle tissue and connective tissue. Several types of tissue work together in the form of an organ to produce a particular function (such as the pumping of the blood by the heart, or as a barrier to the environment as the skin). This pattern continues to a higher level with several organs functioning as an organ system to allow for reproduction, digestion, &c. Many multicelled organisms comprise of several organ systems which coordinate to allow for life. ## The cell The cell theory, first developed in 1839 by Schleiden and Schwann, states that all organisms are composed of one or more cells; all cells come from preexisting cells; all vital functions of an organism occur within cells, and cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells. There are two types of cells, eukaryotic and prokaryotic. Prokaryotic cells are usually singletons, while eukaryotic cells are usually found in multi-cellular organisms. Prokaryotic cells lack a nuclear membrane so DNA is unbound within the cell, eukaryotic cells have nuclear membranes. All cells, whether prokaryotic or eukaryotic, have a membrane, which envelopes the cell, separates its interior from its environment, regulates what moves in and out, and maintains the electric potential of the cell. Inside the membrane, a salty cytoplasm takes up most of the cell volume. All cells possess DNA, the hereditary material of genes, and RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery. There are also other kinds of biomolecules in cells. All cells share several abilities: - Reproduction by cell division (binary fission, mitosis or meiosis). - Use of enzymes and other proteins coded for by DNA genes and made via messenger RNA intermediates and ribosomes. - Metabolism, including taking in raw materials, building cell components, converting energy, molecules and releasing by-products. The functioning of a cell depends upon its ability to extract and use chemical energy stored in organic molecules. This energy is derived from metabolic pathways. - Response to external and internal stimuli such as changes in temperature, pH or nutrient levels. - Cell contents are contained within a cell surface membrane that contains proteins and a lipid bilayer. # Life span One of the basic parameters of organism is its life span. Some animals live as short as one day, while some plants can live thousands of years. Aging is important when determining life span of most organisms, bacterium, a virus or even a prion. # Evolution In biology, the theory of universal common descent proposes that all organisms on Earth are descended from a common ancestor or ancestral gene pool. Evidence for common descent may be found in traits shared between all living organisms. In Darwin's day, the evidence of shared traits was based solely on visible observation of morphologic similarities, such as the fact that all birds have wings, even those which do not fly. Today, there is strong evidence from genetics that all organisms have a common ancestor. For example, every living cell makes use of nucleic acids as its genetic material, and uses the same twenty amino acids as the building blocks for proteins. The universality of these traits strongly suggests common ancestry. The "Last Universal Ancestor" is the name given to the hypothetical single cellular organism or single cell that gave rise to all life on Earth 3.9 to 4.1 billion years ago; however, this hypothesis has since been refuted on many grounds. For example, it was once thought that the genetic code was universal (see: universal genetic code), but differences in the genetic code and differences in how each organism translates nucleic acid sequences into proteins, provide support that there never was any "last universal common ancestor." Back in the early 1970s, evolutionary biologists thought that a given piece of DNA specified the same protein subunit in every living thing, and that the genetic code was thus universal. Since this is something unlikely to happen by chance, it was interpreted as evidence that every organism had inherited its genetic code from a single common ancestor, aka., the "Last Universal Ancestor." In 1979, however, exceptions to the code were found in mitochondria, the tiny energy factories inside cells. Biologists subsequently found exceptions in bacteria and in the nuclei of algae and single-celled animals. It is now clear that the genetic code is not the same in all living things, and that it does not provide powerful evidence that all living things evolved on a single tree of life. Further support that there is no "Last Universal Ancestor" has been provided over the years by Lateral gene transfer in both prokaryote and eukaryote single cell organisms. This is why phylogenetic trees cannot be rooted, why almost all phylogenetic trees have different branching structures, particularly near the base of the tree, and why many organisms have been found with codons and sections of their DNA sequence that are unrelated to any other species. Information about the early development of life includes input from the fields of geology and planetary science. These sciences provide information about the history of the Earth and the changes produced by life. However, a great deal of information about the early Earth has been destroyed by geological processes over the course of time. ## History of life The chemical evolution from self-catalytic chemical reactions to life (see Origin of life) is not a part of biological evolution, but it is unclear at which point such increasingly complex sets of reactions became what we would consider, today, to be living organisms. Not much is known about the earliest developments in life. However, all existing organisms share certain traits, including cellular structure and genetic code. Most scientists interpret this to mean all existing organisms share a common ancestor, which had already developed the most fundamental cellular processes, but there is no scientific consensus on the relationship of the three domains of life (Archaea, Bacteria, Eukaryota) or the origin of life. Attempts to shed light on the earliest history of life generally focus on the behavior of macromolecules, particularly RNA, and the behavior of complex systems. The emergence of oxygenic photosynthesis (around 3 billion years ago) and the subsequent emergence of an oxygen-rich, non-reducing atmosphere can be traced through the formation of banded iron deposits, and later red beds of iron oxides. This was a necessary prerequisite for the development of aerobic cellular respiration, believed to have emerged around 2 billion years ago. In the last billion years, simple multicellular plants and animals began to appear in the oceans. Soon after the emergence of the first animals, the Cambrian explosion (a period of unrivaled and remarkable, but brief, organismal diversity documented in the fossils found at the Burgess Shale) saw the creation of all the major body plans, or phyla, of modern animals. This event is now believed to have been triggered by the development of the Hox genes. About 500 million years ago, plants and fungi colonized the land, and were soon followed by arthropods and other animals, leading to the development of land ecosystems with which we are familiar. The evolutionary process may be exceedingly slow. Fossil evidence indicates that the diversity and complexity of modern life has developed over much of the history of the earth. Geological evidence indicates that the Earth is approximately 4.6 billion years old. Studies on guppies by David Reznick at the University of California, Riverside, however, have shown that the rate of evolution through natural selection can proceed 10 thousand to 10 million times faster than what is indicated in the fossil record.. Such comparative studies however are invariably biased by disparities in the time scales over which evolutionary change is measured in the laboratory, field experiments, and the fossil record. ## Horizontal gene transfer, and the history of life The ancestry of living organisms has traditionally been reconstructed from morphology, but is increasingly supplemented with phylogenetics - the reconstruction of phylogenies by the comparison of genetic (DNA) sequence. "Sequence comparisons suggest recent horizontal transfer of many genes among diverse species including across the boundaries of phylogenetic 'domains'. Thus determining the phylogenetic history of a species can not be done conclusively by determining evolutionary trees for single genes." Biologist Gogarten suggests "the original metaphor of a tree no longer fits the data from recent genome research", therefore "biologists use the metaphor of a mosaic to describe the different histories combined in individual genomes and use metaphor of a net to visualize the rich exchange and cooperative effects of HGT among microbes."	Organism Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] In biology and ecology, an organism (in Greek organon = instrument) is an individual living system (such as animal, plant, fungus or micro-organism). In at least some form, all organisms are capable of reacting to stimuli, reproduction, growth and maintenance as a stable whole (after FAO[1]). An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs. Based on cell type, organisms may be divided into the prokaryotic and eukaryotic groups. The prokaryotes are generally considered to represent two separate domains, called the Bacteria and Archaea, which are not closer to one another than to the eukaryotes. The gap between prokaryotes and eukaryotes is widely considered a major missing link in evolutionary history. Eukaryotic organisms, with a membrane-bounded cell nucleus, also contain organelles, namely mitochondria and (in plants) plastids, generally considered to be derived from endosymbiotic bacteria. A similar symbiogenesis hypothesis has been proposed involving the origins of the cell nucleus, it is described as viral eukaryogenesis. Fungi, animals and plants are examples of species that are eukaryotes.More recently a clade, Neomura, has been proposed, by Thomas Cavalier-Smith, which groups together the Archaea and Eukarya. Cavalier-Smith also proposed that the Neomura evolved from Bacteria, more precisely from Actinobacteria. The phrase complex organism describes any organism with more than one cell. # Semantics The word "organism" may broadly be defined as an assembly of molecules that influence each other in such a way that they function as a more or less stable whole and have properties of life. However, many sources, lexical and scientific, add conditions that are problematic to defining the word. The Oxford English Dictionary defines an organism as "[an] individual animal, plant, or single-celled life form"[2] This definition problematically excludes non-animal and plant multi-cellular life forms such as some fungi and protista. Less controversially, perhaps, it excludes viruses and theoretically-possible man-made non-organic life forms. Chambers Online Reference provides a much broader definition: "any living structure, such as a plant, animal, fungus or bacterium, capable of growth and reproduction"[3]. The definition emphasises life; it allows for any life form, organic or otherwise, to be considered an organism. This does encompass all cellular life, as well as possible synthetic life. This definition does lack anything approximating to the word "individual" which would exclude viruses. Some may use a definition not including cells. For example its definition might be; a structure that has a DNA. This allows different things by definition to be counted as an organism. The word "organism" usually describes an independent collections of systems (for example circulatory, digestive, or reproductive) themselves collections of organs; these are, in turn, collections of tissues, which are themselves made of cells. ## Viruses Viruses are not typically considered to be organisms because they are incapable of "independent" reproduction or metabolism. This controversy is problematic, though, since some parasites and endosymbionts are also incapable of independent life. Although viruses have enzymes and molecules characteristic of living organisms, they are incapable of reproducing outside a host cell and most of their metabolic processes require a host and its 'genetic machinery.' ## Superorganism A superorganism is an organism consisting of many organisms. This is usually meant to be a social unit of eusocial animals, where division of labour is highly specialised and where individuals are not able to survive by themselves for extended periods of time. Ants are the most well known example of such a superorganism. Thermoregulation, a feature usually exhibited by individual organisms, does not occur in individuals or small groups of honeybees of the species Apis mellifera. When these bees pack together in clusters of between 5000 and 40000, the colony can thermoregulate.[4] James Lovelock, with his "Gaia Theory" has paralleled the work of Vladimir Vernadsky, who suggested the whole of the biosphere in some respects can be considered as a superorganism. The concept of superorganism is under dispute, as many biologists maintain that in order for a social unit to be considered an organism by itself, the individuals should be in permanent physical connection to each other, and its evolution should be governed by selection to the whole society instead of individuals. While it's generally accepted that the society of eusocial animals is a unit of natural selection to at least some extent, most evolutionists claim that the individuals are still the primary units of selection. The question remains "What is to be considered the individual?". Darwinians like Richard Dawkins suggest that the individual selected is the "Selfish Gene". Others believe it is the whole genome of an organism. E.O. Wilson has shown that with ant-colonies and other social insects it is the breeding entity of the colony that is selected, and not its individual members. This could apply to the bacterial members of a stromatolite, which, because of genetic sharing, in some way comprise a single gene pool. Gaian theorists like Lynn Margulis would argue this applies equally to the symbiogenesis of the bacterial underpinnings of the whole of the Earth. It would appear, from computer simulations like Daisyworld that biological selection occurs at multiple levels simultaneously. It is also argued that humans are actually a superorganism that includes microorganisms such as bacteria. It is estimated that "the human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own[...] Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-D-erythritol 4-phosphate pathway–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes." [5]. # Organizational terminology All organisms are classified by the science of alpha taxonomy into either taxa or clades. Taxa are ranked groups of organisms which run from the general (domain) to the specific (species). A broad scheme of ranks in hierarchical order is: - Domain - Kingdom - Phylum - Class - Order - Family - Genus - Species To give an example, Homo sapiens is the Latin binomial equating to modern humans. All members of the species sapiens are, at least in theory, genetically able to interbreed. Several species may belong to a genus, but the members of different species within a genus are unable to interbreed to produce fertile offspring. Homo, however, only has one surviving species (sapiens); Homo erectus, Homo neanderthalensis, &c. having become extinct thousands of years ago. Several genera belong to the same family and so on up the hierarchy. Eventually, the relevant kingdom (Animalia, in the case of humans) is placed into one of the three domains depending upon certain genetic and structural characteristics. All living organisms known to science are given classification by this system such that the species within a particular family are more closely related and genetically similar than the species within a particular phylum. # Chemistry Organisms are complex chemical systems, organized in ways that promote reproduction and some measure of sustainability or survival. The molecular phenomena of chemistry are fundamental in understanding organisms, but it is a philosophical error (reductionism) to reduce organismal biology to mere chemistry. It is generally the phenomena of entire organisms that determine their fitness to an environment and therefore the survivability of their DNA based genes. Organisms clearly owe their origin, metabolism, and many other internal functions to chemical phenomena, especially the chemistry of large organic molecules. Organisms are complex systems of chemical compounds which, through interaction with each other and the environment, play a wide variety of roles. Organisms are semi-closed chemical systems. Although they are individual units of life (as the definition requires) they are not closed to the environment around them. To operate they constantly take in and release energy. Autotrophs produce usable energy (in the form of organic compounds) using light from the sun or inorganic compounds while heterotrophs take in organic compounds from the environment. The primary chemical element in these compounds is carbon. The physical properties of this element such as its great affinity for bonding with other small atoms, including other carbon atoms, and its small size makes it capable of forming multiple bonds, make it ideal as the basis of organic life. It is able to form small compounds containing three atoms (such as carbon dioxide) as well as large chains of many thousands of atoms which are able to store data (nucleic acids), hold cells together and transmit information (protein). ## Macromolecules The compounds which make up organisms may be divided into macromolecules and other, smaller molecules. The four groups of macromolecule are nucleic acids, proteins, carbohydrates and lipids. Nucleic acids (specifically deoxyribonucleic acid, or DNA) store genetic data as a sequence of nucleotides. The particular sequence of the four different types of nucleotides (adenine, cytosine, guanine, and thymine) dictate the many characteristics which constitute the organism. The sequence is divided up into codons, each of which is a particular sequence of three nucleotides and corresponds to a particular amino acid. Thus a sequence of DNA codes for a particular protein which, due to the chemical properties of the amino acids of which it is made, folds in a particular manner and so performs a particular function. The following functions of protein have been recognized: - Enzymes, which catalyze all of the reactions of metabolism; - Structural proteins, such as tubulin, or collagen; - Regulatory proteins, such as transcription factors or cyclins that regulate the cell cycle; - Signalling molecules or their receptors such as some hormones and their receptors; - Defensive proteins, which can include everything from antibodies of the immune system, to toxins (e.g., dendrotoxins of snakes), to proteins that include unusual amino acids like canavanine. Lipids make up the membrane of cells which constitutes a barrier, containing everything within the cell and preventing compounds from freely passing into, and out of, the cell. In some multi-cellular organisms they serve to store energy and mediate communication between cells. Carbohydrates also store and transport energy in some organisms, but are more easily broken down than lipids. # Structure All organisms consist of monomeric units called cells; some contain a single cell (unicellular) and others contain many units (multicellular). Multicellular organisms are able to specialise cells to perform specific functions, a group of such cells is tissue the four basic types of which are epithelium, nervous tissue, muscle tissue and connective tissue. Several types of tissue work together in the form of an organ to produce a particular function (such as the pumping of the blood by the heart, or as a barrier to the environment as the skin). This pattern continues to a higher level with several organs functioning as an organ system to allow for reproduction, digestion, &c. Many multicelled organisms comprise of several organ systems which coordinate to allow for life. ## The cell The cell theory, first developed in 1839 by Schleiden and Schwann, states that all organisms are composed of one or more cells; all cells come from preexisting cells; all vital functions of an organism occur within cells, and cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells. There are two types of cells, eukaryotic and prokaryotic. Prokaryotic cells are usually singletons, while eukaryotic cells are usually found in multi-cellular organisms. Prokaryotic cells lack a nuclear membrane so DNA is unbound within the cell, eukaryotic cells have nuclear membranes. All cells, whether prokaryotic or eukaryotic, have a membrane, which envelopes the cell, separates its interior from its environment, regulates what moves in and out, and maintains the electric potential of the cell. Inside the membrane, a salty cytoplasm takes up most of the cell volume. All cells possess DNA, the hereditary material of genes, and RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery. There are also other kinds of biomolecules in cells. All cells share several abilities[6]: - Reproduction by cell division (binary fission, mitosis or meiosis). - Use of enzymes and other proteins coded for by DNA genes and made via messenger RNA intermediates and ribosomes. - Metabolism, including taking in raw materials, building cell components, converting energy, molecules and releasing by-products. The functioning of a cell depends upon its ability to extract and use chemical energy stored in organic molecules. This energy is derived from metabolic pathways. - Response to external and internal stimuli such as changes in temperature, pH or nutrient levels. - Cell contents are contained within a cell surface membrane that contains proteins and a lipid bilayer. # Life span One of the basic parameters of organism is its life span. Some animals live as short as one day, while some plants can live thousands of years. Aging is important when determining life span of most organisms, bacterium, a virus or even a prion. # Evolution Template:Seealso In biology, the theory of universal common descent proposes that all organisms on Earth are descended from a common ancestor or ancestral gene pool. Evidence for common descent may be found in traits shared between all living organisms. In Darwin's day, the evidence of shared traits was based solely on visible observation of morphologic similarities, such as the fact that all birds have wings, even those which do not fly. Today, there is strong evidence from genetics that all organisms have a common ancestor. For example, every living cell makes use of nucleic acids as its genetic material, and uses the same twenty amino acids as the building blocks for proteins. The universality of these traits strongly suggests common ancestry. The "Last Universal Ancestor" is the name given to the hypothetical single cellular organism or single cell that gave rise to all life on Earth 3.9 to 4.1 billion years ago; however, this hypothesis has since been refuted on many grounds. For example, it was once thought that the genetic code was universal (see: universal genetic code), but differences in the genetic code and differences in how each organism translates nucleic acid sequences into proteins, provide support that there never was any "last universal common ancestor." Back in the early 1970s, evolutionary biologists thought that a given piece of DNA specified the same protein subunit in every living thing, and that the genetic code was thus universal. Since this is something unlikely to happen by chance, it was interpreted as evidence that every organism had inherited its genetic code from a single common ancestor, aka., the "Last Universal Ancestor." In 1979, however, exceptions to the code were found in mitochondria, the tiny energy factories inside cells. Biologists subsequently found exceptions in bacteria and in the nuclei of algae and single-celled animals. It is now clear that the genetic code is not the same in all living things, and that it does not provide powerful evidence that all living things evolved on a single tree of life.[7] Further support that there is no "Last Universal Ancestor" has been provided over the years by Lateral gene transfer in both prokaryote and eukaryote single cell organisms. This is why phylogenetic trees cannot be rooted, why almost all phylogenetic trees have different branching structures, particularly near the base of the tree, and why many organisms have been found with codons and sections of their DNA sequence that are unrelated to any other species. Information about the early development of life includes input from the fields of geology and planetary science. These sciences provide information about the history of the Earth and the changes produced by life. However, a great deal of information about the early Earth has been destroyed by geological processes over the course of time. ## History of life The chemical evolution from self-catalytic chemical reactions to life (see Origin of life) is not a part of biological evolution, but it is unclear at which point such increasingly complex sets of reactions became what we would consider, today, to be living organisms. Not much is known about the earliest developments in life. However, all existing organisms share certain traits, including cellular structure and genetic code. Most scientists interpret this to mean all existing organisms share a common ancestor, which had already developed the most fundamental cellular processes, but there is no scientific consensus on the relationship of the three domains of life (Archaea, Bacteria, Eukaryota) or the origin of life. Attempts to shed light on the earliest history of life generally focus on the behavior of macromolecules, particularly RNA, and the behavior of complex systems. The emergence of oxygenic photosynthesis (around 3 billion years ago) and the subsequent emergence of an oxygen-rich, non-reducing atmosphere can be traced through the formation of banded iron deposits, and later red beds of iron oxides. This was a necessary prerequisite for the development of aerobic cellular respiration, believed to have emerged around 2 billion years ago. In the last billion years, simple multicellular plants and animals began to appear in the oceans. Soon after the emergence of the first animals, the Cambrian explosion (a period of unrivaled and remarkable, but brief, organismal diversity documented in the fossils found at the Burgess Shale) saw the creation of all the major body plans, or phyla, of modern animals. This event is now believed to have been triggered by the development of the Hox genes. About 500 million years ago, plants and fungi colonized the land, and were soon followed by arthropods and other animals, leading to the development of land ecosystems with which we are familiar. The evolutionary process may be exceedingly slow. Fossil evidence indicates that the diversity and complexity of modern life has developed over much of the history of the earth. Geological evidence indicates that the Earth is approximately 4.6 billion years old. Studies on guppies by David Reznick at the University of California, Riverside, however, have shown that the rate of evolution through natural selection can proceed 10 thousand to 10 million times faster than what is indicated in the fossil record.[8]. Such comparative studies however are invariably biased by disparities in the time scales over which evolutionary change is measured in the laboratory, field experiments, and the fossil record. ## Horizontal gene transfer, and the history of life The ancestry of living organisms has traditionally been reconstructed from morphology, but is increasingly supplemented with phylogenetics - the reconstruction of phylogenies by the comparison of genetic (DNA) sequence. "Sequence comparisons suggest recent horizontal transfer of many genes among diverse species including across the boundaries of phylogenetic 'domains'. Thus determining the phylogenetic history of a species can not be done conclusively by determining evolutionary trees for single genes." [9] Biologist Gogarten suggests "the original metaphor of a tree no longer fits the data from recent genome research", therefore "biologists [should] use the metaphor of a mosaic to describe the different histories combined in individual genomes and use [the] metaphor of a net to visualize the rich exchange and cooperative effects of HGT among microbes." [10]	https://www.wikidoc.org/index.php/Life_form
f43b03d49557ce9067ebf92470d32f8ffbc3c564	wikidoc	Linalool	Linalool Linalool (Template:IPA2) is a naturally-occurring terpene alcohol chemical found in many flowers and spice plants with many commercial applications, the majority of which are based on its pleasant scent (floral, with a touch of spiciness). It has other names such as β-linalool, linalyl alcohol, linaloyl oxide, p-linalool, allo-ocimenol and 2,6-dimethyl-2,7-octadien-6-ol. ## In nature Over 200 species of plants produce linalool, mainly from the families Lamiaceae (mints, scented herbs), Lauraceae (laurels, cinnamon, rosewood) and Rutaceae (citrus fruits), but also birch trees and other plants, from tropical to boreal climate zones. It was also found in some fungi. ## Enantiomers Linalool has a chiral center at C3 and therefore two stereoisomers: licareol is (S)-(+)-linalool with CAS No. 126–90–9 (PubChem 67179) and coriandrol is (R)-(–)-linalool with CAS No. 126–91–0 (PubChem 13562). Both enantiomeric forms are found in nature: S-linalool is found, for example, as a major constituent of the essential oils of coriander (Coriandrum sativum L. family Apiaceae) seed, palmarosa , and sweet orange (Citrus sinensis Osbeck, family Rutaceae) flowers. R-linalool is present in lavender (Lavandula officinalis Chaix, family Lamiaceae), laurel (Laurus nobilis, family Lauraceae), and sweet basil (Ocimum basilicum, family Lamiaceae), among others. Each enantiomer evokes different neural responses in humans, and therefore are anthropophilically classified as possessing distinct scents. 3S-(+)-linalool is perceived as sweet, floral, petitgrain-like (odour threshold 7.4 ppb) and the 3R-form as more woody and lavender-like (odour threshold 0.8 ppb) ## Biosynthesis In higher plants linalool as other monoterpenoids is produced from isopentenyl pyrophosphate via the universal isoprenoid intermediate geranyl pyrophosphate, through a class of memabrane-bound enzymes named monoterpene synthases. One of these, linalool synthase (LIS), has been reported to produce (S)-linalool in several floral tissues. ## Uses In addition to its use as a scent in domestic products such as soap, detergent, shampoo, and lotion, linalool is also used as a chemical intermediate. One common downstream product of linalool is Vitamin E. # Safety information Linalool should be avoided by people with perfume allergy.	Linalool Template:Chembox new Linalool (Template:IPA2) is a naturally-occurring terpene alcohol chemical found in many flowers and spice plants with many commercial applications, the majority of which are based on its pleasant scent (floral, with a touch of spiciness). It has other names such as β-linalool, linalyl alcohol, linaloyl oxide, p-linalool, allo-ocimenol and 2,6-dimethyl-2,7-octadien-6-ol. ## In nature Over 200 species of plants produce linalool, mainly from the families Lamiaceae (mints, scented herbs), Lauraceae (laurels, cinnamon, rosewood) and Rutaceae (citrus fruits), but also birch trees and other plants, from tropical to boreal climate zones. It was also found in some fungi. ## Enantiomers Linalool has a chiral center at C3 and therefore two stereoisomers: licareol is (S)-(+)-linalool with CAS No. 126–90–9 (PubChem 67179) and coriandrol is (R)-(–)-linalool with CAS No. 126–91–0 (PubChem 13562). Both enantiomeric forms are found in nature: S-linalool is found, for example, as a major constituent of the essential oils of coriander (Coriandrum sativum L. family Apiaceae) seed, palmarosa [Cymbopogon martinii var martinii (Roxb.) Wats., family Poaceae], and sweet orange (Citrus sinensis Osbeck, family Rutaceae) flowers. R-linalool is present in lavender (Lavandula officinalis Chaix, family Lamiaceae), laurel (Laurus nobilis, family Lauraceae), and sweet basil (Ocimum basilicum, family Lamiaceae), among others. Each enantiomer evokes different neural responses in humans, and therefore are anthropophilically classified as possessing distinct scents. 3S-(+)-linalool is perceived as sweet, floral, petitgrain-like (odour threshold 7.4 ppb) and the 3R-form as more woody and lavender-like (odour threshold 0.8 ppb) ## Biosynthesis In higher plants linalool as other monoterpenoids is produced from isopentenyl pyrophosphate via the universal isoprenoid intermediate geranyl pyrophosphate, through a class of memabrane-bound enzymes named monoterpene synthases. One of these, linalool synthase (LIS), has been reported to produce (S)-linalool in several floral tissues. ## Uses In addition to its use as a scent in domestic products such as soap, detergent, shampoo, and lotion, linalool is also used as a chemical intermediate. One common downstream product of linalool is Vitamin E. # Safety information Linalool should be avoided by people with perfume allergy[1].	https://www.wikidoc.org/index.php/Linalool
60c836832730cad689334d35c04329b834ca71f6	wikidoc	Lip balm	Lip balm Lip balm or lip salve is a substance topically applied to the lips of the mouth to relieve chapped or dry lips, angular cheilitis or stomatitis, and cold sores. Lip gloss is similar, but generally has only cosmetic properties. The balm is usually manufactured from beeswax, petroleum jelly, menthol, camphor, scented oils, and various other ingredients. Some manufacturers also add vitamins, alum, salicylic acid, or aspirin. Most lip balms also contain octinoxate, avobenzone, and/or other sunscreens to minimize sun damage. The primary purpose of Lip Balm is to provide an occlusive layer on the lip surface to seal moisture in lips and protect them from external exposure. Dry air, cold temperatuers and wind all have a drying effect on skin by drawing moisture away from the body. Lips are particularly vulnerable because the skin is so thin, and thus they are often the first to present signs of dryness. The occlusives materials like waxes and petroleum jelly prevent moisture loss and maintain lip comfort while flavorants, colorants, sunscreens and various medicaments can provide additional, specific benefits. Lip balm usually comes in small containers; either one in which a finger is used to apply it to the lips, or in 'stick' form (similar to lipstick) which is applied directly to the lips. # Brands - Blistex - Burt's Bees - Bag Balm - Carmex - ChapStick - Labello - Tholene - Vaseline and Vaseline Lip Therapy - Verissima - Sues Salves Sues Salves Lip Butter	Lip balm Lip balm or lip salve is a substance topically applied to the lips of the mouth to relieve chapped or dry lips, angular cheilitis or stomatitis, and cold sores. Lip gloss is similar, but generally has only cosmetic properties. The balm is usually manufactured from beeswax, petroleum jelly, menthol, camphor, scented oils, and various other ingredients. Some manufacturers also add vitamins, alum, salicylic acid, or aspirin. Most lip balms also contain octinoxate, avobenzone, and/or other sunscreens to minimize sun damage. The primary purpose of Lip Balm is to provide an occlusive layer on the lip surface to seal moisture in lips and protect them from external exposure. Dry air, cold temperatuers and wind all have a drying effect on skin by drawing moisture away from the body. Lips are particularly vulnerable because the skin is so thin, and thus they are often the first to present signs of dryness. The occlusives materials like waxes and petroleum jelly prevent moisture loss and maintain lip comfort while flavorants, colorants, sunscreens and various medicaments can provide additional, specific benefits. Lip balm usually comes in small containers; either one in which a finger is used to apply it to the lips, or in 'stick' form (similar to lipstick) which is applied directly to the lips. # Brands - Blistex - Burt's Bees[1] - Bag Balm - Carmex - ChapStick - Labello - Tholene - Vaseline and Vaseline Lip Therapy - Verissima - Sues Salves Sues Salves Lip Butter	https://www.wikidoc.org/index.php/Lip_balm
19eba7d87cf0ebe5ae681d5dae4112d31071e60d	wikidoc	Lipaemia	Lipaemia Synonyms and keywords: lipemia, hyperlipaemia, hyperlipemia, hyperlipidaemia, hyperlipidemia, hyperlipoidaemia, hyperlipoidemia, lipemia, lipidaemia, lipidemia, lipoidaemia, lipoidemia # Overview Lipaemia is defined as an abnormally high concentration of lipids in the blood, usually in the form of very low density lipoproteins (VLDLs) or chylomicrons. Characteristically the blood plasma may appear white or milky in colour due to the presence of fat. Triglycerides in the 400–800 mg/dl range may produce visible lipaemia. # Causes ## Common Causes - Eating fatty foods. This may happen soon after a fatty meal, although patients who are very overweight may constantly have mildly lipaemic blood - Diabetes mellitus - Alcoholism - Medications such as steroids, oestrogens, and protease inhibitors (for HIV infection) - Chronic renal failure - Hypothyroidism - Pancreatitis and other pancreatic or hepatic disorders - Multiple myeloma - Primary biliary cirrhosis - Systemic lupus erythematosus - Total parenteral nutrition # Interference with laboratory testing Assays and analysers routinely used for biochemical and haematological laboratory tests can be classified according to how they work: - Assays involving light scattering (these are affected by lipaemia) - Assays involving volume displacement (these are affected by lipaemia) - Assays involving the aqueous fraction (these are not affected by lipaemia) - Assays involving optical clot detection methods (these are affected by lipaemia) - Mechanical or electromechanical means of clot detection (these are not affected by lipaemia) In lipaemia, chylomicrons and VLDLs are suspended in the blood and scatter light, producing the characteristic cloudiness or turbidity similar to that seen in milk. This suspension interferes with laboratory instrument systems that function based on light detection or scatter (turbidimetry and nephelometry). The lipid particles also exert a volume effect and can interfere with laboratory assays involving volume displacement. This effect can cause a pseudo-hyponatremia for example. Assays involving the aqueous fraction, such as methods involving ionselective electrodes are not affected by lipaemia. Using optical clot detection methods, as is commonly used in determining prothrombin time and activated partial thromboplastin time, lipemia may result in artificial prolongation of clotting times. Mechanical or electromechanical means of clot detection are not affected by lipemia. # Tests affected by lipaemia Lipemia artificially increases values of the following analytes: - Glucose - Phosphorus - Bilirubin - Uric acid - Total protein - HbA1c - Fructosamine - Triglycerides - D-dimer Lipaemia artificially decreases values of the following analytes: - Sodium (] - HDL cholesterol - Ceruloplasmin - Prealbumin - Transferrin # Dealing with a lipaemic sample Many instruments employ an optical detection method to measure the optical density of a sample. If a sample is lipaemic and the baseline optical density is too high, the instrument will not report a result. Other techniques will be needed to analyse the sample: - Ask the patient to fast for 12 hours before sample collection - Dilution. Interference by lipaemia is dependent on the dilution of samples used in the reaction. The higher the dilution that can be afforded, the lesser the chance of lipid-based interference. For example, samples diluted 1:20 can show lipid interference, which may be avoided using dilutions such as 1:400. - Ultracentrifugation can separate out a fatty layer which is discarded before normal analysis - Solvent extraction. Extraction of lipids from blood specimens with n-hexane before coagulation testing has been described but is not common practice in clinical laboratories	Lipaemia Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: lipemia, hyperlipaemia, hyperlipemia, hyperlipidaemia, hyperlipidemia, hyperlipoidaemia, hyperlipoidemia, lipemia, lipidaemia, lipidemia, lipoidaemia, lipoidemia # Overview Lipaemia is defined as an abnormally high concentration of lipids in the blood, usually in the form of very low density lipoproteins (VLDLs) or chylomicrons. Characteristically the blood plasma may appear white or milky in colour due to the presence of fat. Triglycerides in the 400–800 mg/dl range may produce visible lipaemia. # Causes ## Common Causes - Eating fatty foods. This may happen soon after a fatty meal, although patients who are very overweight may constantly have mildly lipaemic blood - Diabetes mellitus - Alcoholism - Medications such as steroids, oestrogens, and protease inhibitors (for HIV infection) - Chronic renal failure - Hypothyroidism - Pancreatitis and other pancreatic or hepatic disorders - Multiple myeloma - Primary biliary cirrhosis - Systemic lupus erythematosus - Total parenteral nutrition # Interference with laboratory testing Assays and analysers routinely used for biochemical and haematological laboratory tests can be classified according to how they work: - Assays involving light scattering (these are affected by lipaemia) - Assays involving volume displacement (these are affected by lipaemia) - Assays involving the aqueous fraction (these are not affected by lipaemia) - Assays involving optical clot detection methods (these are affected by lipaemia) - Mechanical or electromechanical means of clot detection (these are not affected by lipaemia) In lipaemia, chylomicrons and VLDLs are suspended in the blood and scatter light, producing the characteristic cloudiness or turbidity similar to that seen in milk. This suspension interferes with laboratory instrument systems that function based on light detection or scatter (turbidimetry and nephelometry). The lipid particles also exert a volume effect and can interfere with laboratory assays involving volume displacement. This effect can cause a pseudo-hyponatremia for example. Assays involving the aqueous fraction, such as methods involving ionselective electrodes are not affected by lipaemia. Using optical clot detection methods, as is commonly used in determining prothrombin time and activated partial thromboplastin time, lipemia may result in artificial prolongation of clotting times. Mechanical or electromechanical means of clot detection are not affected by lipemia. # Tests affected by lipaemia Lipemia artificially increases values of the following analytes: - Glucose - Phosphorus - Bilirubin - Uric acid - Total protein - HbA1c - Fructosamine - Triglycerides - D-dimer Lipaemia artificially decreases values of the following analytes: - Sodium ([[pseudohyponatremia)]] - HDL cholesterol - Ceruloplasmin - Prealbumin - Transferrin # Dealing with a lipaemic sample Many instruments employ an optical detection method to measure the optical density of a sample. If a sample is lipaemic and the baseline optical density is too high, the instrument will not report a result. Other techniques will be needed to analyse the sample: - Ask the patient to fast for 12 hours before sample collection - Dilution. Interference by lipaemia is dependent on the dilution of samples used in the reaction. The higher the dilution that can be afforded, the lesser the chance of lipid-based interference. For example, samples diluted 1:20 can show lipid interference, which may be avoided using dilutions such as 1:400. - Ultracentrifugation can separate out a fatty layer which is discarded before normal analysis - Solvent extraction. Extraction of lipids from blood specimens with n-hexane before coagulation testing has been described but is not common practice in clinical laboratories	https://www.wikidoc.org/index.php/Lipaemia
6ec6f5d0ff82001312e89aa15cc266f90eb85de9	wikidoc	Lipedema	Lipedema Lipedema is a disorder of adipose tissue distinguished by five characteristics: 1) it can be inherited; 2) it occurs almost exclusively in women; 3) it can occur in women of all sizes, from the anorexic to the morbidly obese; 3) it involves the excess deposit and expansion of fat cells in an unusual and particular pattern – bilateral, symmetrical and usually from the waist to a distinct line just above the ankles; and 4) unlike the “normal” fat of obesity, lipedemic fat cannot be lost through diet and exercise. Surgery is highly controversial, and in many cases, can make the condition worse. Lipedema usually is triggered at puberty, but can trigger or worsen during or after pregnancy, at peri-menopause, and following gynecological surgery. If lipedema is diagnosed early, which currently is very rare, it is possible to prevent a significant expansion of lipedemic fat cells, and to alert patients to their heightened risk for obesity so they can take appropriate action. Estimates of the incidence of lipedema vary widely, and range as high as 11% of the post-puberty female population. Even if the number were only 5%, that would mean more than 6 million women in the United States alone. # Differentiating lipedema from other diseases Lipedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lymphatic filariasis, myxedema, cellulitis and causes of generalized edema. # Symptoms Patients tend to gain weight in lipedemic areas and lose it in non-lipedemic areas. Obese lipedema patients who undergo bariatric surgery lose fat primarily from the waist up. Even anorexic women can starve and exercise away "normal" fat but retain lipedemic fat. The classic early-stage lipedemic profile is a woman who looks like a size 8 from the waist up and a size 16 from the waist down with disproportionately large, column-like legs. As lipedema progresses, patients become increasingly heavy in the lower body. The additional, expanding fat cells interfere with the pathways of lymphatic vessels, and patients can develop secondary lymphedema, a condition known as lipo-lymphedema. Many lipedema patients cannot tolerate the compression garments associated with conventional lymphedema treatment because the underlying lipedemic fat is very painful, and those patients therefore are at risk for the side effects of uncontrolled lymphedema, including recurring blood infections and fibrosis. Women with lipedema also are at very high risk for obesity because the lipedemic fat cannot be lost, and because as the condition worsens, patients become progressively less mobile. # Treatment Treatment is designed primarily to address the secondary lymphedema part of the lipedema patient’s condition. This treatment includes a course of manual lymphatic drainage and bandaging by a lymphedema therapist, followed by the wearing of custom-fitted compression garments or devices - usually stockings and sometimes biker shorts. Compression prevents recurrence of lymphedema, and in some lipedema patients can reduce the pain of lipedemic fat. There is no cure for lipedema. # History Although first identified in the United States, at the Mayo Clinic in 1940, lipedema is barely known in that country – to physicians or to the patients who have the disease. Lipedema often is confused with obesity, and a significant number of patients currently diagnosed as obese are believed to have lipedema, either instead of or in addition to obesity. Lipedema has multiple spellings. "Lipedema" is the American spelling, while "Lipoedema" is used in Britain and Europe. "Lipodema" is also used occasionally.	Lipedema Lipedema is a disorder of adipose tissue distinguished by five characteristics: 1) it can be inherited; 2) it occurs almost exclusively in women; 3) it can occur in women of all sizes, from the anorexic to the morbidly obese; 3) it involves the excess deposit and expansion of fat cells in an unusual and particular pattern – bilateral, symmetrical and usually from the waist to a distinct line just above the ankles; and 4) unlike the “normal” fat of obesity, lipedemic fat cannot be lost through diet and exercise. Surgery is highly controversial, and in many cases, can make the condition worse. Lipedema usually is triggered at puberty, but can trigger or worsen during or after pregnancy, at peri-menopause, and following gynecological surgery. If lipedema is diagnosed early, which currently is very rare, it is possible to prevent a significant expansion of lipedemic fat cells, and to alert patients to their heightened risk for obesity so they can take appropriate action. Estimates of the incidence of lipedema vary widely, and range as high as 11% of the post-puberty female population. Even if the number were only 5%, that would mean more than 6 million women in the United States alone. # Differentiating lipedema from other diseases Lipedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lymphatic filariasis, myxedema, cellulitis and causes of generalized edema. # Symptoms Patients tend to gain weight in lipedemic areas and lose it in non-lipedemic areas. Obese lipedema patients who undergo bariatric surgery lose fat primarily from the waist up. Even anorexic women can starve and exercise away "normal" fat but retain lipedemic fat. The classic early-stage lipedemic profile is a woman who looks like a size 8 from the waist up and a size 16 from the waist down with disproportionately large, column-like legs. As lipedema progresses, patients become increasingly heavy in the lower body. The additional, expanding fat cells interfere with the pathways of lymphatic vessels, and patients can develop secondary lymphedema, a condition known as lipo-lymphedema. Many lipedema patients cannot tolerate the compression garments associated with conventional lymphedema treatment because the underlying lipedemic fat is very painful, and those patients therefore are at risk for the side effects of uncontrolled lymphedema, including recurring blood infections and fibrosis. Women with lipedema also are at very high risk for obesity because the lipedemic fat cannot be lost, and because as the condition worsens, patients become progressively less mobile. # Treatment Treatment is designed primarily to address the secondary lymphedema part of the lipedema patient’s condition. This treatment includes a course of manual lymphatic drainage and bandaging by a lymphedema therapist, followed by the wearing of custom-fitted compression garments or devices - usually stockings and sometimes biker shorts. Compression prevents recurrence of lymphedema, and in some lipedema patients can reduce the pain of lipedemic fat. There is no cure for lipedema. # History Although first identified in the United States, at the Mayo Clinic in 1940, lipedema is barely known in that country – to physicians or to the patients who have the disease. Lipedema often is confused with obesity, and a significant number of patients currently diagnosed as obese are believed to have lipedema, either instead of or in addition to obesity. Lipedema has multiple spellings. "Lipedema" is the American spelling, while "Lipoedema" is used in Britain and Europe. "Lipodema" is also used occasionally.	https://www.wikidoc.org/index.php/Lipedema
65546361eef5d5c903517bc3a9eb2452b3e6c651	wikidoc	Lipiodol	Lipiodol # Overview Lipiodol is an iodinated, radio-opaque contrast material that is used to outline structures in radiological investigations. It is used in chemoembolization applications as a contrast agent in follow-up imaging. It has an additional use in gastric variceal obliteration as a dilutant that does not affect polymerization of cyanoacrylate. Lipiodol is also used in lymphangiography, the imaging of the lymphatic system. Historically it was often used as a contrast media at hysterosalpingography(HSG). This is an investigation to determine tubal patency as part of the investigation of subfertility. It became less commonly utilised in the 1960s to 1980s because the more modern water soluble media give images that are easier to interpret. There is also an important safety issue with lipiodol in that intravasation (leakage) of the fluid into the venous system has caused patients to be uwell in the past because of intravasation. Recently there has been an increasing interest in the use of lipiodol as a therapeutic agent in the management of unexplained infertility called lipiodol flushing. There have been a small number of studies that suggest that flushing the media through the tubes gives a short term rise in fecundity in patients with unexplained infertility. A recent systematic review has suggested a significant increase in fertility, especially in those women who have endometriosis when using lipiodol flushing (Johnson N.P et al).	Lipiodol # Overview Lipiodol is an iodinated, radio-opaque contrast material that is used to outline structures in radiological investigations. It is used in chemoembolization applications as a contrast agent in follow-up imaging. It has an additional use in gastric variceal obliteration as a dilutant that does not affect polymerization of cyanoacrylate. Lipiodol is also used in lymphangiography, the imaging of the lymphatic system. Historically it was often used as a contrast media at hysterosalpingography(HSG). This is an investigation to determine tubal patency as part of the investigation of subfertility. It became less commonly utilised in the 1960s to 1980s because the more modern water soluble media give images that are easier to interpret. There is also an important safety issue with lipiodol in that intravasation (leakage) of the fluid into the venous system has caused patients to be uwell in the past because of intravasation. Recently there has been an increasing interest in the use of lipiodol as a therapeutic agent in the management of unexplained infertility called lipiodol flushing. There have been a small number of studies that suggest that flushing the media through the tubes gives a short term rise in fecundity in patients with unexplained infertility. A recent systematic review has suggested a significant increase in fertility, especially in those women who have endometriosis when using lipiodol flushing (Johnson N.P et al). Template:WH Template:WS	https://www.wikidoc.org/index.php/Lipiodol
966e77a1f492f3bb9df0468bd2c19abae65bf66a	wikidoc	Liposome	Liposome # Overview A liposome is a spherical vesicle composed of a bilayer membrane. In biology, this specifically refers to a membrane composed of a phospholipid and cholesterol bilayer (see on the right). Liposomes can be composed of naturally-derived phospholipids with mixed lipid chains (like egg phosphatidylethanolamine), or of pure surfactant components like DOPE (dioleoylphosphatidylethanolamine). Liposomes, usually but not by definition, contain a core of aqueous solution; lipid spheres that contain no aqueous material are called micelles, however, reverse micelles can be made to encompass an aqueous environment. # Etymology The name liposome is derived from two Greek words 'Lipid' meaning fat and 'Soma' meaning body. The word liposome does not in itself denote any size characteristics as is frequently presumed and therefore is not an alternative to a Nanosome. Furthermore the term liposome does not necessarily mean that it must contain lipophobic contents, such as water, although it usually does. # Discovery Liposomes were first described by British haematologist Sir. Alec D Bangham in 1961 (published 1964), at the Babraham institute, Cambridge. They were discovered when Bangham and R. W. Horne were testing the institute's new electron microscope by adding negative stain to dry phospholipids. The resemblance to the plasmalemma was obvious, and the microscope pictures served as the first real evidence for the cell membrane being a bilayer lipid structure. # Application Liposomes are used for drug delivery due to their unique properties. A liposome encapsulates a region on aqueous solution inside a hydrophobic membrane; dissolved hydrophilic solutes can not readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents. By making liposomes in a solution of DNA or drugs (which would normally be unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer. Liposomes can also be designed to deliver drugs in other ways. Liposomes that contain low (or high) pH can be constructed such that dissolved aqueous drugs will be charged in solution (i.e., the pH is outside the drug's pI range). As the pH naturally neutralizes within the liposome (protons can pass through some membranes), the drug will also be neutralized, allowing it to freely pass through a membrane. These liposomes work to deliver drug by diffusion rather than by direct cell fusion. Another strategy for liposome drug delivery is to target endocytosis events. Liposomes can be made in a particular size range that makes them viable targets for natural macrophage phagocytosis. These liposomes may be digested while in the magrophage's phagosome, thus releasing its drug. Liposomes can also be decorated with opsonins and ligands to activate endocytosis in other cell types. - The use of liposomes for transformation or transfection of DNA into a host cell is known as lipofection. # Targeting cancer Another interesting property of liposomes are their natural ability to target cancer. The endothelial wall of all healthy human blood vessels are encapsulated by endothelial cells that are bound together by tight junctions. These tight junctions stop any large particle of in the blood from leaking out of the vessel. Tumour vessels do not contain the same level of seal between cells and are diagnostically leaky. This ability is known as the Enhanced Permeability and Retention effect. Liposomes of certain sizes, typically less than 400nm, can rapidly enter tumour sites from the blood, but are kept in the bloodstream by the endothelial wall in healthy tissue vasculature. Anti-cancer drugs such as Doxorubicin (Doxil) and Daunorubicin (Daunoxome) are currently being marketed in liposome delivery systems. # Manufacturing Liposomes can be created by sonicating phospholipids in water. Low shear rates create multilamellar liposomes, which have many layers like an onion. Continued high-shear sonication tends to form smaller unilamellar liposomes. In this technique, the liposome contents are the same as the contents of the aqueous phase. Sonication is generally considered a "gross" method of preparation, and newer methods such as extrusion are employed to produce materials for human use. # Prospect Further advances in liposome research have been able to allow liposomes to avoid detection by the body's immune system, specifically, the cells of reticuloendothelial system (RES). These liposomes are known as "stealth liposomes", and are constructed with PEG (Polyethylene Glycol) studding the outside of the membrane. The PEG coating, which is inert in the body, allows for longer circulatory life for the drug delivery mechanism. However, research currently seeks to investigate at what amount of PEG coating the PEG actually hinders binding of the liposome to the delivery site. In addition to a PEG coating, most stealth liposomes also have some sort of biological species attached as a ligand to the liposome in order to enable binding via a specific expression on the targeted drug delivery site. These targeting ligands could be monoclonal antibodies (making an immunoliposome), vitamins, or specific antigens. Targeted liposomes can target nearly any cell type in the body and deliver drugs that would naturally be systemically delivered. Naturally toxic drugs can be much less toxic if delivered only to diseased tissues.	Liposome # Overview A liposome is a spherical vesicle composed of a bilayer membrane. In biology, this specifically refers to a membrane composed of a phospholipid and cholesterol bilayer (see on the right). Liposomes can be composed of naturally-derived phospholipids with mixed lipid chains (like egg phosphatidylethanolamine), or of pure surfactant components like DOPE (dioleoylphosphatidylethanolamine). Liposomes, usually but not by definition, contain a core of aqueous solution; lipid spheres that contain no aqueous material are called micelles, however, reverse micelles [1] can be made to encompass an aqueous environment. # Etymology The name liposome is derived from two Greek words 'Lipid' meaning fat and 'Soma' meaning body. The word liposome does not in itself denote any size characteristics as is frequently presumed and therefore is not an alternative to a Nanosome. Furthermore the term liposome does not necessarily mean that it must contain lipophobic contents, such as water, although it usually does. # Discovery Liposomes were first described by British haematologist Sir. Alec D Bangham in 1961 (published 1964), at the Babraham institute, Cambridge. They were discovered when Bangham and R. W. Horne were testing the institute's new electron microscope by adding negative stain to dry phospholipids. The resemblance to the plasmalemma was obvious, and the microscope pictures served as the first real evidence for the cell membrane being a bilayer lipid structure. # Application Liposomes are used for drug delivery due to their unique properties. A liposome encapsulates a region on aqueous solution inside a hydrophobic membrane; dissolved hydrophilic solutes can not readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents. By making liposomes in a solution of DNA or drugs (which would normally be unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer. Liposomes can also be designed to deliver drugs in other ways. Liposomes that contain low (or high) pH can be constructed such that dissolved aqueous drugs will be charged in solution (i.e., the pH is outside the drug's pI range). As the pH naturally neutralizes within the liposome (protons can pass through some membranes), the drug will also be neutralized, allowing it to freely pass through a membrane. These liposomes work to deliver drug by diffusion rather than by direct cell fusion. Another strategy for liposome drug delivery is to target endocytosis events. Liposomes can be made in a particular size range that makes them viable targets for natural macrophage phagocytosis. These liposomes may be digested while in the magrophage's phagosome, thus releasing its drug. Liposomes can also be decorated with opsonins and ligands to activate endocytosis in other cell types. - The use of liposomes for transformation or transfection of DNA into a host cell is known as lipofection. # Targeting cancer Another interesting property of liposomes are their natural ability to target cancer. The endothelial wall of all healthy human blood vessels are encapsulated by endothelial cells that are bound together by tight junctions. These tight junctions stop any large particle of in the blood from leaking out of the vessel. Tumour vessels do not contain the same level of seal between cells and are diagnostically leaky. This ability is known as the Enhanced Permeability and Retention effect. Liposomes of certain sizes, typically less than 400nm, can rapidly enter tumour sites from the blood, but are kept in the bloodstream by the endothelial wall in healthy tissue vasculature. Anti-cancer drugs such as Doxorubicin (Doxil) and Daunorubicin (Daunoxome) are currently being marketed in liposome delivery systems. # Manufacturing Liposomes can be created by sonicating phospholipids in water. Low shear rates create multilamellar liposomes, which have many layers like an onion. Continued high-shear sonication tends to form smaller unilamellar liposomes. In this technique, the liposome contents are the same as the contents of the aqueous phase. Sonication is generally considered a "gross" method of preparation, and newer methods such as extrusion are employed to produce materials for human use. # Prospect Further advances in liposome research have been able to allow liposomes to avoid detection by the body's immune system, specifically, the cells of reticuloendothelial system (RES). These liposomes are known as "stealth liposomes", and are constructed with PEG (Polyethylene Glycol) studding the outside of the membrane. The PEG coating, which is inert in the body, allows for longer circulatory life for the drug delivery mechanism. However, research currently seeks to investigate at what amount of PEG coating the PEG actually hinders binding of the liposome to the delivery site. In addition to a PEG coating, most stealth liposomes also have some sort of biological species attached as a ligand to the liposome in order to enable binding via a specific expression on the targeted drug delivery site. These targeting ligands could be monoclonal antibodies (making an immunoliposome), vitamins, or specific antigens. Targeted liposomes can target nearly any cell type in the body and deliver drugs that would naturally be systemically delivered. Naturally toxic drugs can be much less toxic if delivered only to diseased tissues.	https://www.wikidoc.org/index.php/Liposomal
f39ec4c5842180f69148ae3146003eb62778f592	wikidoc	Ringworm	Ringworm # Overview Ringworm, also known as "Tinea", is an infection of the skin, characterized by a reddish to brownish raised or bumpy patch of skin that may be lighter in the center, giving the appearance of a 'ring'. Contrary to its name, ringworm is not caused by a worm but by parasitic fungi (Dermatophytosis). It can exist anywhere on the body. Fungi are tiny organisms that survive by eating plant or animal material, those that cause parasitic infection (dermatophytes) feed on keratin, the material found in the outer layer of skin, hair, and nails. These fungi thrive best on skin that is moist, hot, and hidden from the light. Together with the other dermatophytosis, up to 20 percent of the population has one of these infections at any given moment. # Transmission Ringworm is very common, especially among children, and may be spread by skin-to-skin contact, as well as via contact with contaminated items such as hairbrushes or through the use of the same toilet seat as an infected individual. Ringworm spreads readily, as those infected are contagious even before they show symptoms of the disease. Participants in contact sports such as wrestling have a risk of contracting the fungal infection through skin-to-skin contact. Ringworm is mildly contagious. Ringworm is also a common infection in domestic animals, especially farm animals, dogs and cats. Humans can contract ringworm from these animals as humans are in close contact with them. Chickens may also be a source, due to the dirty conditions in which many poultry must live in which ringworm may thrive. Ringworm can also be caught from other humans, both by direct contact and by prolonged contact with flakes of shed skin (from sharing clothes or from house dust, for instance). To catch ringworm, you have to be exposed to it and you have to be susceptible. Some people are much more susceptible than others. Those with eczema or other skin problems get ringworm more easily because the protective barrier of the skin's outer layer is less intact. Children are more susceptible before puberty. Some people are genetically predisposed, and can get it easily throughout life. # Symptoms and diagnosis The best known sign of ringworm in people is the appearance of one or more red raised itchy patches with defined edges, not unlike the herald rash of Pityriasis rosea. These patches are often lighter in the center, taking on the appearance of a ring. If the infected area involves the scalp or beard area, then bald patches may become evident. The affected area may become itchy for periods of time. Doctors can diagnose ringworm on sight, or they may take a skin scraping, or in the case of animal ringworm or tinea capitis, examine plucked hairs for fungal elements. This is examined under a microscope, or put on an agar plate in a microbiology laboratory and allowed to grow. Some of the fungi fluoresce under a black light examination. In domestic animals, ringworm can cause a variety of symptoms, but most cases show scaling and patches of hair loss. Some cats can be carriers, but show no symptoms. Sometimes a ringworm infection may cause skin lesions in a part of the body that is remote from the actual infection. Such lesions are called "dermatophytids". The lesions themselves are fungus-free, and normally disappear upon treatment of the actual infection. The most common example is an eruption in the hands resulting from a fungus infection of the feet. Dermatophytids are essentially a generalized allergic reaction to the fungus. - Plucked hair treated with KOH showing ectothrix spores and hyphae from a case of feline ringworm - Specialized agar plate, called Dermatophyte Test Medium is used to culture and identify ringworm organisms - Tinea corporis ringworm # Differential diagnosis Ringworm infection must be differentiated from other diseases presenting with an erythmatous, scaly, annular and pruritic rash. The differentials include the following: # Treatment Topical antifungal drugs containing miconazole (Daktarin, Micatin & Monistat), clotrimazole, terbinafine (Lamisil), butenafine and tolnaftate (Tinactin), many available without a prescription, are used to clear up the infection. Pyrithione zinc, found in Head and Shoulders shampoo, is a very effective treatment for ringworm on the scalp and can be used as a body wash to assist in overall treatment. On September 28, 2007, the U.S. Food and Drug Administration stated that Terbinafine (Lamisil by Novartis AG) is a new treatment approved for use by children aged 4 up. Antifungal granules can be sprinkled on a child's food to treat ringworm of the scalp, Tinea capitis. Treatment may be obstructed by itching, burning, cracking, and scaling that accompany this condition and prevent effective treatment. Ointments may be mixed with hydrocortisone creams such as Cortaid appear to reduce inflammation and speed recovery, but not always. Fungal infections may take a while to clear up, but most ringworm infections should see improvement in a week or two. Types affecting the nails or scalp are very difficult to treat due to fungal infection in follicle roots or under the nail itself. Griseofulvin is a traditional drug used to treat ringworm in both animals and people. It can be very effective, but likely requires a prescription and may produce side effects. In cats and cattle, sulfurated lime rinses are often used to treat ringworm; and dilute povidone-iodine may be used as a wash in cattle. Enilconazole, as a rinse, is an effective ringworm treatment available in many countries for treating animals. Lufenuron, the active ingredient in Program oral flea treatment, is also commonly prescribed by vets to treat ringworm infections in cats and dogs. ## Folk remedies Numerous folk remedies have been promoted for the treatment of Ringworm, many of them involving potentially dangerous caustic or acidic ingredients. These remedies generally take the approach of trying to burn away the fungal infection with mild acid preparations, soothing the symptoms with herbal poultices, or applying oils or drawing salves believed to have antibiotic or healing properties, such as tea tree oil. The efficacy of any of these traditional remedies cannot be assessed since they have not undergone rigorous clinical testing. Indeed, some may cause greater harm than the fungal infection they are intended to treat. # Prevention Fungi thrive in warm, moist areas, such as locker rooms and swimming pools, and in skin folds. The fungi may be present without any symptoms. To prevent ringworm: - Do not share clothing, sports equipment, towels, or sheets. If you think you have been exposed to ringworm, wash your clothes in hot water with fungus-killing (fungicidal) soap. - Shower and shampoo thoroughly after any sport that requires skin-to-skin contact. - Wrestlers should regularly inspect the skin before practice, use protective bandages over infections while practicing or avoid competition until 1 week after symptoms resolve, and thoroughly disinfect gym pads and equipment. - Wear loose-fitting cotton clothing and change underwear at least once a day. - Keep your skin clean and dry. Always dry yourself completely after showers or baths. - Take your pet to the vet if it has patches of missing hair, which could be a sign of a fungal infection. - Continue topical remedies for 2 to 4 weeks after symptoms have resolved.	Ringworm Template:Seealso Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Ringworm, also known as "Tinea", is an infection of the skin, characterized by a reddish to brownish raised or bumpy patch of skin that may be lighter in the center, giving the appearance of a 'ring'. Contrary to its name, ringworm is not caused by a worm but by parasitic fungi (Dermatophytosis). It can exist anywhere on the body. Fungi are tiny organisms that survive by eating plant or animal material, those that cause parasitic infection (dermatophytes) feed on keratin, the material found in the outer layer of skin, hair, and nails. These fungi thrive best on skin that is moist, hot, and hidden from the light. Together with the other dermatophytosis, up to 20 percent of the population has one of these infections at any given moment. # Transmission Ringworm is very common, especially among children, and may be spread by skin-to-skin contact, as well as via contact with contaminated items such as hairbrushes or through the use of the same toilet seat as an infected individual. Ringworm spreads readily, as those infected are contagious even before they show symptoms of the disease. Participants in contact sports such as wrestling have a risk of contracting the fungal infection through skin-to-skin contact. Ringworm is mildly contagious. Ringworm is also a common infection in domestic animals, especially farm animals, dogs and cats. Humans can contract ringworm from these animals as humans are in close contact with them. Chickens may also be a source, due to the dirty conditions in which many poultry must live in which ringworm may thrive. Ringworm can also be caught from other humans, both by direct contact and by prolonged contact with flakes of shed skin (from sharing clothes or from house dust, for instance). To catch ringworm, you have to be exposed to it and you have to be susceptible. Some people are much more susceptible than others. Those with eczema or other skin problems get ringworm more easily because the protective barrier of the skin's outer layer is less intact. Children are more susceptible before puberty. Some people are genetically predisposed, and can get it easily throughout life. # Symptoms and diagnosis The best known sign of ringworm in people is the appearance of one or more red raised itchy patches with defined edges, not unlike the herald rash of Pityriasis rosea. These patches are often lighter in the center, taking on the appearance of a ring. If the infected area involves the scalp or beard area, then bald patches may become evident. The affected area may become itchy for periods of time. Doctors can diagnose ringworm on sight, or they may take a skin scraping, or in the case of animal ringworm or tinea capitis, examine plucked hairs for fungal elements. This is examined under a microscope, or put on an agar plate in a microbiology laboratory and allowed to grow. Some of the fungi fluoresce under a black light examination. In domestic animals, ringworm can cause a variety of symptoms, but most cases show scaling and patches of hair loss. Some cats can be carriers, but show no symptoms. Sometimes a ringworm infection may cause skin lesions in a part of the body that is remote from the actual infection. Such lesions are called "dermatophytids". The lesions themselves are fungus-free, and normally disappear upon treatment of the actual infection. The most common example is an eruption in the hands resulting from a fungus infection of the feet. Dermatophytids are essentially a generalized allergic reaction to the fungus. - Plucked hair treated with KOH showing ectothrix spores and hyphae from a case of feline ringworm - Specialized agar plate, called Dermatophyte Test Medium is used to culture and identify ringworm organisms - Tinea corporis ringworm [1] # Differential diagnosis Ringworm infection must be differentiated from other diseases presenting with an erythmatous, scaly, annular and pruritic rash. The differentials include the following: # Treatment Topical antifungal drugs containing miconazole (Daktarin, Micatin & Monistat), clotrimazole, terbinafine (Lamisil), butenafine and tolnaftate (Tinactin), many available without a prescription, are used to clear up the infection. Pyrithione zinc, found in Head and Shoulders shampoo, is a very effective treatment for ringworm on the scalp and can be used as a body wash to assist in overall treatment. On September 28, 2007, the U.S. Food and Drug Administration stated that Terbinafine (Lamisil by Novartis AG) is a new treatment approved for use by children aged 4 up. Antifungal granules can be sprinkled on a child's food to treat ringworm of the scalp, Tinea capitis.[2] Treatment may be obstructed by itching, burning, cracking, and scaling that accompany this condition and prevent effective treatment. Ointments may be mixed with hydrocortisone creams such as Cortaid appear to reduce inflammation and speed recovery, but not always. Fungal infections may take a while to clear up, but most ringworm infections should see improvement in a week or two. Types affecting the nails or scalp are very difficult to treat due to fungal infection in follicle roots or under the nail itself. Griseofulvin is a traditional drug used to treat ringworm in both animals and people. It can be very effective, but likely requires a prescription and may produce side effects. In cats and cattle, sulfurated lime rinses are often used to treat ringworm; and dilute povidone-iodine may be used as a wash in cattle. Enilconazole, as a rinse, is an effective ringworm treatment available in many countries for treating animals. Lufenuron, the active ingredient in Program oral flea treatment, is also commonly prescribed by vets to treat ringworm infections in cats and dogs. ## Folk remedies Numerous folk remedies have been promoted for the treatment of Ringworm, many of them involving potentially dangerous caustic or acidic ingredients. These remedies generally take the approach of trying to burn away the fungal infection with mild acid preparations, soothing the symptoms with herbal poultices, or applying oils or drawing salves believed to have antibiotic or healing properties, such as tea tree oil. The efficacy of any of these traditional remedies cannot be assessed since they have not undergone rigorous clinical testing. Indeed, some may cause greater harm than the fungal infection they are intended to treat. # Prevention Fungi thrive in warm, moist areas, such as locker rooms and swimming pools, and in skin folds. The fungi may be present without any symptoms. To prevent ringworm: - Do not share clothing, sports equipment, towels, or sheets. If you think you have been exposed to ringworm, wash your clothes in hot water with fungus-killing (fungicidal) soap. - Shower and shampoo thoroughly after any sport that requires skin-to-skin contact. - Wrestlers should regularly inspect the skin before practice, use protective bandages over infections while practicing or avoid competition until 1 week after symptoms resolve, and thoroughly disinfect gym pads and equipment. - Wear loose-fitting cotton clothing and change underwear at least once a day. - Keep your skin clean and dry. Always dry yourself completely after showers or baths. - Take your pet to the vet if it has patches of missing hair, which could be a sign of a fungal infection. - Continue topical remedies for 2 to 4 weeks after symptoms have resolved.	https://www.wikidoc.org/index.php/List_of_tinea_infections
3174d39a8280169e27109b2b8a740579739ddf38	wikidoc	Lisuride	Lisuride # Overview Lisuride (brand name in Germany Dopergin) is an anti-Parkinson's drug of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogenmaleate salt. Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the Parkinsonian disability. Preliminary trials suggest that the dermal application of lisuride may be useful in the treatment of Parkinson's disease. Lisuride is not currently available in the US. Lisuride (Dopergin, Proclacam, Revanil) is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogen maleate salt. Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the Parkinsonian disability. Preliminary trials suggest that the dermal application of lisuride may be useful in the treatment of Parkinson's disease. As lisuride is very poorly absorbed when take orally and has a short half-life, continuous transdermal administration offers significant advantages and could make the compound a far more consistent therapeutic. Lisuride is not currently available in the US, as the drug was not a commercial success in comparison with other dopamine receptor agonist anti-parkinsonian compounds. It is still used clinically in a number of countries in the EU and is still commercially available in the UK and China. A Study has failed to find any association between lisuride and fibrotic cardiac valvulopathy. # Mode of action Lisuride is a dopamine and serotonin receptor partial agonist. It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A and 5-HT2A/C receptors. While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD, it lacks the psychedelic effects of its sister compound. It has been suggested that this may be because lisuride acts as an agonist at 5-HT1A and 5-HT2A subtypes but behaves as an antagonist at 5-HT2C, inhibiting the psychedelic effect. Newer findings suggest that the lack of psychedelic action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G-proteins are involved. Lisurid behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer. GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors. # Commercial names # History Synthesis of lisuride was first described in 1960. # Indications - Parkinson's Disease	Lisuride Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Lisuride (brand name in Germany Dopergin) is an anti-Parkinson's drug of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogenmaleate salt. Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the Parkinsonian disability. Preliminary trials suggest that the dermal application of lisuride may be useful in the treatment of Parkinson's disease. Lisuride is not currently available in the US. Lisuride (Dopergin, Proclacam, Revanil) is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogen maleate salt. Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the Parkinsonian disability. Preliminary trials suggest that the dermal application of lisuride may be useful in the treatment of Parkinson's disease. As lisuride is very poorly absorbed when take orally and has a short half-life, continuous transdermal administration offers significant advantages and could make the compound a far more consistent therapeutic. Lisuride is not currently available in the US, as the drug was not a commercial success in comparison with other dopamine receptor agonist anti-parkinsonian compounds. It is still used clinically in a number of countries in the EU and is still commercially available in the UK and China. A Study has failed to find any association between lisuride and fibrotic cardiac valvulopathy.[1] # Mode of action Lisuride is a dopamine and serotonin receptor partial agonist. It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A[2] and 5-HT2A/C receptors.[3] While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD,[4] it lacks the psychedelic effects of its sister compound. It has been suggested that this may be because lisuride acts as an agonist at 5-HT1A and 5-HT2A subtypes but behaves as an antagonist at 5-HT2C, inhibiting the psychedelic effect.[5] Newer findings suggest that the lack of psychedelic action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G-proteins are involved.[6][7] Lisurid behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer.[8] GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors. # Commercial names # History Synthesis of lisuride was first described in 1960. # Indications - Parkinson's Disease	https://www.wikidoc.org/index.php/Lisuride
15382c0edc296fc539c037119bfbc7f74bc333b3	wikidoc	Literacy	Literacy The traditional definition of literacy is considered to be the ability to read and write, or the ability to use language to read, write, listen, and speak. In modern contexts, the word refers to reading and writing at a level adequate for communication, or at a level that lets one understand and communicate ideas in a literate society, so as to take part in that society. The United Nations Educational, Scientific and Cultural Organization (UNESCO) has drafted the following definition: "Literacy is the ability to identify, understand, interpret, create, communicate and compute, using printed and written materials associated with varying contexts. Literacy involves a continuum of learning to enable an individual to achieve his or her goals, to develop his or her knowledge and potential, and to participate fully in the wider society." # Economics Many policy analystsTemplate:Weasel-inline consider literacy rates a crucial measure of a region's human capital. This claim is made on the grounds that literate people can be trained less expensively than illiterate people, generally have a higher socio-economic status and enjoy better health and employment prospects. Policy makers also argue that literacy increases job opportunities and access to higher education. In Kerala, India, for example, female and child mortality rates declined dramatically in the 1960s, when girls who were educated in the education reforms after 1948 began to raise families. Recent researchers,Template:Weasel-inline however, argue that correlations such as the one listed above may have more to do with the overall effects of schooling rather than literacy alone. In addition to the potential for literacy to increase wealth, wealth may promote literacy, through cultural norms and easier access to schools and tutoring services. # Illiteracy Illiteracy is the condition of not being able to read or write, and in modern times is seen as a social problem to be solved through education. ## World literacy rates 20% of the world population was illiterate in 1998 by the United Nations definition - the inability to read and write a simple sentence in any language. Asian, Arab and Sub-Saharan African countries are regions with the lowest literacy rates at about 10% to 12%. East Asia and Latin America have illiteracy rates in the 10 to 15% region while developed countries have illiteracy rates of a few percent. Within ethnically homogeneous regions, literacy rates can vary widely from country or region to region. This often coincides with the region's wealth or urbanization, though many factors play a role. Among the Arab states, 19.8% of men and 41.1% of women were not literate as of 2006. ## India According to the the 2001 India census, India's national literacy is only 65.2 percent. Literacy drive is spreading slowly to other states. India's youth (age 15 to 24) literacy rate was 76.4% between 2000 and 2004. At current rates India will take no less than 20 years for a literacy of 95%.. Literacy in India is not homogeneous. The southern state of Kerala recorded a 90.92% literacy rate in 2001, while the northern state of Bihar was considerably lower at 47.53%. India's overall adult literacy rate (61.3% in 2002), is slightly higher than other nations in South Asia, except Sri Lanka's 92%, with Nepal next at 44%, Pakistan at 50-54% and Bangladesh the lowest at 43.1% Many Indians have argued that illiteracy, especially in the rural areas, gives undue advantage to contemporary politicians, who will take advantage of the situation to become corrupt and neglect issues of socio-economic development.. ## United States There are various definitions of literacy. Governments may label individuals who can read a couple of thousand simple words they learned by sight in the first four grades in school as literate. But the most comprehensive study of U.S. adult literacy ever commissioned by the U.S. government proves that such adults are functionally illiterate--they cannot read well enough to hold a good job. Several studies have shown that millions of Americans never read another book after leaving school. A five-year, $14 million study of U.S. adult literacy involving lengthy interviews of U.S. adults, the most comprehensive study of literacy ever commissioned by the U.S. government, was released in September 1993 revealing the shocking details. It involved lengthy interviews of over 26,700 adults statistically balanced for age, gender, ethnicity, education level, and location (urban, suburban, or rural) in twelve states across the U.S. and was designed to represent the U.S. population as a whole. This study showed the percentages of U.S. adults who worked full-time, part-time, were unemployed, or who had given up looking for a job and were no longer in the work force, and it showed the average hourly wages for those who were employed. These data were grouped by literacy level--how well the interviewees responded to material written in English--and indicated that 40 to 44 million of the 191 million U.S. adults (21 to 23 percent of them) in the least literate group earned a yearly average of $2105 and about 50 million adults (25 to 28 percent of them) in the next-least literate of the five literacy groups earned a yearly average of $5225 at a time when the U.S. Census Bureau considered the poverty level threshold for an individual to be $7363 per year. The report of a follow-up study by the same group of researchers using a smaller database (19,714 interviewees) was released in 2006 that showed no statistically significant improvement in U.S. adult literacy. These studies prove that a minimum of 46 and a maximum of 51 percent of U.S. adults read so poorly that they earn significantly below the threshold poverty level for an individual. The only reason we do not see that number of families in poverty is that most low-income families have more than one employed adult and almost all low-income families receive financial assistance from the government, family, friends, or charitable organizations. Many U.S. citizens believe that the U.S. literacy rate is much higher than these reports would indicate. The World Fact Book prepared by the CIA claims that the U.S. literacy rate is 99 percent, but defines literacy as being able to read and write when a person is 15 years old or older. A person who can only read a few hundred--or even a couple of thousand--simple words learned in the first four grades in school, is only marginally literate. Jonathan Kozol, in his book Illiterate America, states that there may not be any intentional deception, but explains that the census bureau reported literacy rates of 99 percent based on personal interviews of a relatively small portion of the population and on written responses to census bureau mailings. If the interviewees or written responders had completed fifth grade they were considered literate. In the 1970 census, for example, five percent had less than a fifth grade education. The census bureau considered eighty percent of those with less than a fifth grade education as being literate and reported a 99 percent literacy rate. In the 1980 and 1990 censuses, most of the census bureau calculations of literacy were based upon grade completion. They used written questionnaires and a small number of home visits and telephone interviews. If a respondent stated that they had completed less than five grades, they were asked if they could read and write, and their unsubstantiated answer was recorded as a fact. Kozol explains that this method of determining literacy is quite certain to underestimate illiteracy for the following reasons: - Illiterate people would not respond to written forms and their family members--also likely to be illiterate--would not either. - Illiterate people are less likely to have telephones than the general public, because of unemployment or low paying jobs. - Illiterate people may distrust anyone knocking on their door or calling on the telephone and seeking information because they are often hounded by bill collectors, salesmen, and others because of their financial condition and because they may have been cheated as a result of their illiteracy. Therefore they cannot be expected to give accurate answers to questions asked by census bureau workers they do not know, especially if the answers are embarrassing. - Grade level completion does not equal grade level competence. - Those who have no permanent home address, no telephone, no post office box, and no regular job--a condition shared by more than six million adults, most of whom are illiterate--cannot be found by the census bureau in time to be included in the count. # History The history of literacy goes back several thousand years, but before the industrial revolution finally made cheap paper and cheap books available to all classes in industrialized countries in the mid-nineteenth century, only a small percentage of the population in these countries were literate. Up until that point, materials associated with literacy were prohibitively expensive for people other than wealthy individuals and institutions. For example, in England in 1841, 33% of men and 44% of women signed marriage certificates with their mark as they were unable to write. Only in 1870 was government-financed public education made available in England. What constitutes literacy has changed throughout history. It has only recently become expected and desirable to be fully literate and undesirable to be illiterate. At one time, a literate person was one who could sign his or her name. At other points, literacy was measured only by the ability to read and write Latin (regardless of a person's ability to read or write his or her vernacular), or by the ability to read the Bible. The benefit of clergy in common law systems became dependent on reading a particular passage. These concepts of literacy have much to do with the invention of the printing press, and it is noted that between 1500 and 1800, styles of reading changed. Briggs and Burke (2002) give examples of five types of reading changes : The emergence of critical reading, as reading was once taken literally, dangerous reading, where reading was seen as dangerous in the hands of less educated groups such as women or 'the common people', creative reading, the application of content via the reader's individual paradigm, extensive reading, especially seen in the research of a particular topic, and private reading, where formatting of texts changed to embrace the notion of browsing. This privatization is an aspect of the rise of individualism. Literacy has also been used as a way to sort populations and control who has access to power. Because literacy permits learning and communication that oral and sign language alone cannot, illiteracy has been enforced in some places as a way of preventing unrest or revolution. During the Civil War era in the United States, white citizens in many areas banned teaching slaves to read or write presumably understanding the power of literacy. In the years following the Civil War, the ability to read and write was used to determine whether one had the right to vote. This effectively served to prevent former slaves from joining the electorate and maintained the status quo. In 1964, educator Paulo Freire was arrested, expelled, and exiled from his native Brazil because of his work in teaching Brazilian peasants to read. From another perspective, the historian Harvey Graff has argued that the introduction of mass schooling was in part an effort to control the type of literacy that the working class had access to. That is, literacy learning was increasing outside of formal settings (such as schools) and this uncontrolled, potentially critical reading could lead to increased radicalization of the populace. Mass schooling was meant to temper and control literacy, not spread it. ## Examples of highly literate cultures in the past India and China were advanced in literacy and made many scientific advancements. Many universities like Nalanda provided education to pupils and scholars from all around the world. The large amount of graffiti found at Roman sites such as Pompeii, shows that at least a large minority of the population would have been literate. Because of its emphasis on the individual reading of the Qur'an in the original Arabic alphabet many Islamic countries have known a comparatively high level of literacy during most of the past twelve centuries. In Islamic edict (or Fatwa), to be literate is an individual religious obligation. In the Middle Ages, literacy rates among Jews in Europe were much higher than in the surrounding Christian populations. Most Jewish males at least learned to read and write Hebrew. Judaism places great importance on the study of holy texts, the Tanakh and the Talmud. In New England, the literacy rate was over 50 percent during the first half of the 17th century, and it rose to 70 percent by 1710. By the time of the American Revolution, it was around 90 percent. This is seen by some as a side effect of the Puritan belief in the importance of Bible reading. In Wales, the literacy rate rocketed during the 18th century, when Griffith Jones ran a system of circulating schools, with the aim of enabling everyone to read the Bible (in Welsh). It is claimed that, in 1750, Wales had the highest literacy rate of any country in the world. Historically, the literacy rate has also been high in the Lutheran countries of Northern Europe. The 1686 church law (kyrkolagen) of the Kingdom of Sweden (which at the time included all of modern Sweden, Finland, and Estonia) enforced literacy on the people and a hundred years later, by the end of the 18th century, the literacy rate was close to 100 percent. Even before the 1686 law, literacy was widespread in Sweden. However, the ability to read did not automatically imply ability to write, and as late as the 19th century many Swedes, especially women, could not write. This proves even more difficult, because many literary historians measure literacy rates based on the ability that people had to sign their own names. Online Video: The Spread, Rise and Fall of Early Literacy # Teaching literacy Literacy comprises a number of subskills, including phonological awareness, decoding, fluency, comprehension, and vocabulary. Mastering each of these subskills is necessary for students to become proficient readers. ## Alphabetic principle and English orthography Beginning readers must understand the concept of the alphabetic principle in order to master basic reading skills. A writing system is said to be alphabetic if it uses symbols to represent individual language sounds. In contrast, logographic writing systems (such as Chinese) use a symbol to represent an entire word, and syllabic writing systems (such as Japanese kana) use a symbol to represent a single syllable. Alphabetic writing systems vary in complexity. For example, Spanish is an alphabetic writing system that has a nearly perfect one-to-one correspondence of symbols to individual sounds. In Spanish, most of the time words are spelled the way they sound, that is, word spellings are almost always regular. English, on the other hand, is far more complex in that it does not have a one-to-one correspondence between symbols and sounds. English has individual sounds that can be represented by more than one symbol or symbol combination. For example, the long \|a\| sound can be represented by a-consonant-e as in ate, -ay as in hay, -ea as in steak, -ey as in they, -ai as in pain, and -ei as in vein. In addition, there are many words with irregular spelling and many homophones (words that sound the same but have different meanings and often different spellings as well). Pollack Pickeraz (1963) asserted that there are 45 phonemes in the English language, and that the 26 letters of the English alphabet can represent the 45 phonemes in about 350 ways. It should be noted that the irregularity of English spelling is largely an artifact of how the language developed. English is a Germanic language; however, it has substantial influences from Latin, Greek, and French, among others. Over its history, English adopted vocabulary from many languages, and the imported words usually follow the spelling patterns of their language of origin. Advanced phonics instruction includes studying words according to their origin, and how to determine the correct spelling of a word using its language of origin. Clearly, the complexity of English orthography makes it more difficult for children to learn decoding and encoding rules, and more difficult for teachers to teach them. However, effective word recognition relies on the basic understanding that letters represent the sounds of spoken language, that is, word recognition relies on the reader's understanding of the alphabetic principle. ### Phonics Phonics is an instructional technique that teaches readers to attend to the letters or groups of letters that make up words. So, to read the word throat using phonics, each grapheme (a letter or letters that represent one sound) is examined separately: th says /θ/, r says /ɹ/, oa says /oʊ/, and t says /t/. There are various methods for teaching phonics. A common way to teach this is to have the novice reader pronounce each individual sound and "blend" them to pronounce the whole word. This is called synthetic phonics. There are many programs that use this approach. A widely-known program is SRA/McGraw-Hill's DISTAR program (now called Reading Mastery). The Orton-Gillingham method, Lindamood-Bell Phoneme Sequencing Program, and the Wilson reading system are other phonics programs. British educator Nellie Dale is credited with creating one of the earliest programs designed to teach basic reading skills, in the late 19th century. In addition to teaching phonological awareness and sound-symbol correspondence, comprehensive phonics programs also include instruction in irregular words, the 6 syllable types, morphology (root words, prefixes, suffixes, etc) and word origin. ### Whole language Because English spelling has so many irregularities and exceptions, advocates of whole language recommend that novice readers should learn a little about the individual letters in words, especially the consonants and the "short vowels." Teachers provide this knowledge opportunistically, in the context of stories that feature many instances of a particular letter. This is known as "embedded phonics." Children use their letter-sound knowledge in combination with context to read new and difficult words. Programs that use a whole language approach include Reading Recovery and Guided reading. ### Which approach is better? The answer to this question is often debated. Scientific research in reading has tended to support the value of teaching phonics, although reading experts from all perspectives believe that time spent reading--a key element of whole language--is very important. Advocates of whole language have dismissed this scientific research for many different reasons. One common complaint is that scientific education researchers rely on randomized studies (similar in design to those done in medicine) and do not value descriptive research that has demonstrated the value of whole language approaches. In the United States, the National Reading Panel was convened in an attempt to determine which approach was best. It found that phonics was more effective than embedded phonics or no phonics, but it only used experimental and quasi-experimental research (it did not include qualitative research), so the whole language community remained skeptical of its conclusions. The debate continues. Consideration should be given to alternative methods of teaching reading since neither the phonics method, the whole word or whole language method, nor any combination of them is completely successful with every student. See Reading education. ## Why learning to read is hard Many children of average and above average intelligence experience difficulty when learning to read. According to Dr. Grover Whitehurst, Assistant Secretary, U.S. Department of Education, learning to read is difficult for several reasons. First, reading requires the mastery of a code that maps human speech sounds to written symbols, and this code is not readily apparent or easy to understand. Second, reading is not a natural process; it was invented by humans fairly recently in our development. The human brain is wired for spoken language, but it is not wired to process the code of written language. Third, confusion can be introduced at the time of instruction by teachers who do not understand what the code is or how it needs to be taught. One reason that mastery of the code that maps human speech sounds to written symbols is so difficult is that English spelling contains so many irregularities and exceptions to the rules. However, when English spelling rules take into account syllable structure, phonetics, and accents, there are literally dozens of rules that are 75% or more reliable. Some phonics spelling advocates claim that English is more than 80% phonetic.Template:Who This is true is more than one grapheme (letter) is allowed per phoneme; otherwise, English is a little more than 20 percent phonetic. In addition, Dr. Diane McGuinness’ book Why Our Children Can’t Read explains the complex logic that is required to learn to read English. Unlike many alphabetic languages, there are tens of thousands of different syllables in English, with sixteen different syllable patterns in English: (C=consonant, V=vowel) CV, CCV, CCCV, CVC, CCVC, CCCVC, CVCC, CVCCC, CCVCC, CCVCCC, CCCVCCC, CCCVCC, VCCC, VCC, VC, and V. There are two or more syllables in most English words. Each syllable can have one of the sixteen syllable patterns. If each vowel and each consonant in each of these patterns consistently represented the same phoneme (one-to-one mapping), there would be nothing in the logic of these syllables that would be beyond the abilities of most four- or five-year-olds. But they do not. English spelling also has one-to-many and many-to-one mapping. This requires a type of logic that most children do not develop until they are eleven or twelve years old. The types of logic required for one-to-many and many-to-one mapping are: (1) the logic of “classes” (categories where objects or events that are similar are grouped) and “relations” (where objects share some features but not all features, e.g. all poodles are dogs, but not all dogs are poodles) and (2) “propositional logic,” which involves combining both the classes and relations types of logic. This requires the ability to think of the same item in more than one way at the same time. These combinations require the use of relational terms such as “and,” “or,” “not,” “if—then,” and “if and only if” in formal statements of propositional logic, e.g. if an H follows the T, then say /TH/ as in thin or then; but if any other letter or no letter follows the T, then say /T/ as in top or ant. It takes most students learning to read English at least two to two-and-one-half years to learn enough words so that they can read most written material easily enough that they enjoy reading, read often, and thereby become fluent readers. ## Reading comprehension Many educators in the USA believe that children need to learn to analyze text (comprehend it) even before they can read it on their own, and comprehension instruction generally begins in pre-Kindergarten or Kindergarten. But other US educators consider this reading approach to be completely backward for very young children, arguing that the children must learn how to decode the words in a story through phonics before they can analyze the story itself. During the last century comprehension lessons usually comprised students answering teachers' questions, writing responses to questions on their own, or both. The whole group version of this practice also often included "round robin reading," wherein teachers called on individual students to read a portion of the text (and sometimes following a set order). In the last quarter of the 20th century, evidence accumulated that the read-test methods assessed comprehension more than they taught it. The associated practice of "round robin" reading has also been questioned and eliminated by many educators. Instead of using the prior read-test method, research studies have concluded that there are much more effective ways to teach comprehension. Much work has been done in the area of teaching novice readers a bank of "reading strategies," or tools to interpret and analyze text. There is not a definitive set of strategies, but common ones include summarizing what you have read, monitoring your reading to make sure it is still making sense, and analyzing the structure of the text (e.g., the use of headings in science text). Some programs teach students how to self monitor whether they are understanding and provide students with tools for fixing comprehension problems. Instruction in comprehension strategy use often involves the gradual release of responsibility, wherein teachers initially explain and model strategies. Over time, they give students more and more responsibility for using the strategies until they can use them independently. This technique is generally associated with the idea of self-regulation and reflects social cognitive theory, originally conceptualized by Albert Bandura. # Broader and complementary definitions Traditional definitions of literacy consider the ability to "read, write, spell, listen, and speak." Some have argued that the definition of literacy should be expanded. For example, in the United States, the National Council of Teachers of English and the International Reading Association have added "visually representing" to the traditional list of competencies. Similarly, in Scotland, literacy has been defined as: "The ability to read and write and use numeracy, to handle information, to express ideas and opinions, to make decisions and solve problems, as family members, workers, citizens and lifelong learners." A basic literacy standard in many societies is the ability to read the newspaper. Increasingly, communication in commerce or society in general requires the ability to use computers and other digital technologies. Since the 1990s, when the Internet came into wide use in the United States, some have asserted that the definition of literacy should include the ability to use tools such as web browsers, word processing programs, and text messages. Similar expanded skill sets have been called multimedia literacy, computer literacy, information literacy, and technacy. "Arts literacy" programs exist in some places in the United States, Australia, Canada, and Finland.Template:Facts Other genres under study by academia include critical literacy, media literacy, and health literacy Some scholarsTemplate:Weasel-inline argue that literacy necessarily includes the cultural, political, and historical contexts of the community in which communication takes place.	Literacy The traditional definition of literacy is considered to be the ability to read and write, or the ability to use language to read, write, listen, and speak. In modern contexts, the word refers to reading and writing at a level adequate for communication, or at a level that lets one understand and communicate ideas in a literate society, so as to take part in that society. The United Nations Educational, Scientific and Cultural Organization (UNESCO) has drafted the following definition: "Literacy is the ability to identify, understand, interpret, create, communicate and compute, using printed and written materials associated with varying contexts. Literacy involves a continuum of learning to enable an individual to achieve his or her goals, to develop his or her knowledge and potential, and to participate fully in the wider society." # Economics Many policy analystsTemplate:Weasel-inline consider literacy rates a crucial measure of a region's human capital. This claim is made on the grounds that literate people can be trained less expensively than illiterate people, generally have a higher socio-economic status[1] and enjoy better health and employment prospects. Policy makers also argue that literacy increases job opportunities and access to higher education. In Kerala, India, for example, female and child mortality rates declined dramatically in the 1960s, when girls who were educated in the education reforms after 1948 began to raise families. Recent researchers,Template:Weasel-inline however, argue that correlations such as the one listed above may have more to do with the overall effects of schooling rather than literacy alone. In addition to the potential for literacy to increase wealth, wealth may promote literacy, through cultural norms and easier access to schools and tutoring services.[citation needed] # Illiteracy Illiteracy is the condition of not being able to read or write, and in modern times is seen as a social problem to be solved through education. ## World literacy rates 20% of the world population was illiterate in 1998 by the United Nations definition - the inability to read and write a simple sentence in any language.[citation needed] Asian, Arab and Sub-Saharan African countries are regions with the lowest literacy rates at about 10% to 12%. East Asia and Latin America have illiteracy rates in the 10 to 15% region while developed countries have illiteracy rates of a few percent. Within ethnically homogeneous regions, literacy rates can vary widely from country or region to region. This often coincides with the region's wealth or urbanization, though many factors play a role. Among the Arab states, 19.8% of men and 41.1% of women were not literate as of 2006.[2] ## India According to the the 2001 India census, India's national literacy is only 65.2 percent.[3] [4] Literacy drive is spreading slowly to other states.[5] India's youth (age 15 to 24) literacy rate was 76.4% between 2000 and 2004.[6] At current rates India will take no less than 20 years for a literacy of 95%.[7]. Literacy in India is not homogeneous. The southern state of Kerala recorded a 90.92% literacy rate in 2001, [8] while the northern state of Bihar was considerably lower at 47.53%.[9] India's overall adult literacy rate (61.3% in 2002), is slightly higher than other nations in South Asia, except Sri Lanka's 92%, [10] with Nepal next at 44%, Pakistan at 50-54% [1][2] and Bangladesh the lowest at 43.1% [3] Many Indians have argued that illiteracy, especially in the rural areas, gives undue advantage to contemporary politicians, who will take advantage of the situation to become corrupt and neglect issues of socio-economic development.[4]. ## United States There are various definitions of literacy. Governments may label individuals who can read a couple of thousand simple words they learned by sight in the first four grades in school as literate. But the most comprehensive study of U.S. adult literacy ever commissioned by the U.S. government proves that such adults are functionally illiterate--they cannot read well enough to hold a good job. Several studies have shown that millions of Americans never read another book after leaving school. A five-year, $14 million study of U.S. adult literacy involving lengthy interviews of U.S. adults, the most comprehensive study of literacy ever commissioned by the U.S. government,[11] was released in September 1993 revealing the shocking details. It involved lengthy interviews of over 26,700 adults statistically balanced for age, gender, ethnicity, education level, and location (urban, suburban, or rural) in twelve states across the U.S. and was designed to represent the U.S. population as a whole. This study showed the percentages of U.S. adults who worked full-time, part-time, were unemployed, or who had given up looking for a job and were no longer in the work force, and it showed the average hourly wages for those who were employed. These data were grouped by literacy level--how well the interviewees responded to material written in English--and indicated that 40 to 44 million of the 191 million U.S. adults (21 to 23 percent of them) in the least literate group earned a yearly average of $2105 and about 50 million adults (25 to 28 percent of them) in the next-least literate of the five literacy groups earned a yearly average of $5225 at a time when the U.S. Census Bureau considered the poverty level threshold for an individual to be $7363 per year.[12] The report of a follow-up study by the same group of researchers using a smaller database (19,714 interviewees) was released in 2006 that showed no statistically significant improvement in U.S. adult literacy.[13] These studies prove that a minimum of 46 and a maximum of 51 percent of U.S. adults read so poorly that they earn significantly below the threshold poverty level for an individual. The only reason we do not see that number of families in poverty is that most low-income families have more than one employed adult and almost all low-income families receive financial assistance from the government, family, friends, or charitable organizations. Many U.S. citizens believe that the U.S. literacy rate is much higher than these reports would indicate. The World Fact Book prepared by the CIA[14] claims that the U.S. literacy rate is 99 percent, but defines literacy as being able to read and write when a person is 15 years old or older. A person who can only read a few hundred--or even a couple of thousand--simple words learned in the first four grades in school, is only marginally literate. Jonathan Kozol, in his book Illiterate America, states that there may not be any intentional deception, but explains[15] that the census bureau reported literacy rates of 99 percent based on personal interviews of a relatively small portion of the population and on written responses to census bureau mailings. If the interviewees or written responders had completed fifth grade they were considered literate. In the 1970 census, for example, five percent had less than a fifth grade education. The census bureau considered eighty percent of those with less than a fifth grade education as being literate and reported a 99 percent literacy rate. In the 1980 and 1990 censuses, most of the census bureau calculations of literacy were based upon grade completion. They used written questionnaires and a small number of home visits and telephone interviews. If a respondent stated that they had completed less than five grades, they were asked if they could read and write, and their unsubstantiated answer was recorded as a fact. Kozol explains that this method of determining literacy is quite certain to underestimate illiteracy for the following reasons: - Illiterate people would not respond to written forms and their family members--also likely to be illiterate--would not either. - Illiterate people are less likely to have telephones than the general public, because of unemployment or low paying jobs. - Illiterate people may distrust anyone knocking on their door or calling on the telephone and seeking information because they are often hounded by bill collectors, salesmen, and others because of their financial condition and because they may have been cheated as a result of their illiteracy. Therefore they cannot be expected to give accurate answers to questions asked by census bureau workers they do not know, especially if the answers are embarrassing. - Grade level completion does not equal grade level competence. - Those who have no permanent home address, no telephone, no post office box, and no regular job--a condition shared by more than six million adults, most of whom are illiterate--cannot be found by the census bureau in time to be included in the count. # History The history of literacy goes back several thousand years, but before the industrial revolution finally made cheap paper and cheap books available to all classes in industrialized countries in the mid-nineteenth century, only a small percentage of the population in these countries were literate. Up until that point, materials associated with literacy were prohibitively expensive for people other than wealthy individuals and institutions. For example, in England in 1841, 33% of men and 44% of women signed marriage certificates with their mark as they were unable to write. Only in 1870 was government-financed public education made available in England. What constitutes literacy has changed throughout history. It has only recently become expected and desirable to be fully literate and undesirable to be illiterate.[citation needed] At one time, a literate person was one who could sign his or her name. At other points, literacy was measured only by the ability to read and write Latin (regardless of a person's ability to read or write his or her vernacular), or by the ability to read the Bible. The benefit of clergy in common law systems became dependent on reading a particular passage. These concepts of literacy have much to do with the invention of the printing press, and it is noted that between 1500 and 1800, styles of reading changed. Briggs and Burke (2002) give examples of five types of reading changes [16]: The emergence of critical reading, as reading was once taken literally, dangerous reading, where reading was seen as dangerous in the hands of less educated groups such as women or 'the common people', creative reading, the application of content via the reader's individual paradigm, extensive reading, especially seen in the research of a particular topic, and private reading, where formatting of texts changed to embrace the notion of browsing. This privatization is an aspect of the rise of individualism. Literacy has also been used as a way to sort populations and control who has access to power. Because literacy permits learning and communication that oral and sign language alone cannot, illiteracy has been enforced in some places as a way of preventing unrest or revolution. During the Civil War era in the United States, white citizens in many areas banned teaching slaves to read or write presumably understanding the power of literacy. In the years following the Civil War, the ability to read and write was used to determine whether one had the right to vote. This effectively served to prevent former slaves from joining the electorate and maintained the status quo. In 1964, educator Paulo Freire was arrested, expelled, and exiled from his native Brazil because of his work in teaching Brazilian peasants to read. From another perspective, the historian Harvey Graff has argued that the introduction of mass schooling was in part an effort to control the type of literacy that the working class had access to. That is, literacy learning was increasing outside of formal settings (such as schools) and this uncontrolled, potentially critical reading could lead to increased radicalization of the populace. Mass schooling was meant to temper and control literacy, not spread it. ## Examples of highly literate cultures in the past Template:Cleanup-merge India and China were advanced in literacy and made many scientific advancements. Many universities like Nalanda provided education to pupils and scholars from all around the world. The large amount of graffiti found at Roman sites such as Pompeii, shows that at least a large minority of the population would have been literate. Because of its emphasis on the individual reading of the Qur'an in the original Arabic alphabet many Islamic countries have known a comparatively high level of literacy during most of the past twelve centuries. In Islamic edict (or Fatwa), to be literate is an individual religious obligation. In the Middle Ages, literacy rates among Jews in Europe were much higher than in the surrounding Christian populations. Most Jewish males at least learned to read and write Hebrew. Judaism places great importance on the study of holy texts, the Tanakh and the Talmud. In New England, the literacy rate was over 50 percent during the first half of the 17th century, and it rose to 70 percent by 1710. By the time of the American Revolution, it was around 90 percent. This is seen by some as a side effect of the Puritan belief in the importance of Bible reading. In Wales, the literacy rate rocketed during the 18th century, when Griffith Jones ran a system of circulating schools, with the aim of enabling everyone to read the Bible (in Welsh). It is claimed that, in 1750, Wales had the highest literacy rate of any country in the world. Historically, the literacy rate has also been high in the Lutheran countries of Northern Europe. The 1686 church law (kyrkolagen) of the Kingdom of Sweden (which at the time included all of modern Sweden, Finland, and Estonia) enforced literacy on the people and a hundred years later, by the end of the 18th century, the literacy rate was close to 100 percent. Even before the 1686 law, literacy was widespread in Sweden. However, the ability to read did not automatically imply ability to write, and as late as the 19th century many Swedes, especially women, could not write. This proves even more difficult, because many literary historians measure literacy rates based on the ability that people had to sign their own names. Online Video: The Spread, Rise and Fall of Early Literacy # Teaching literacy Literacy comprises a number of subskills, including phonological awareness, decoding, fluency, comprehension, and vocabulary. Mastering each of these subskills is necessary for students to become proficient readers. ## Alphabetic principle and English orthography Beginning readers must understand the concept of the alphabetic principle in order to master basic reading skills. A writing system is said to be alphabetic if it uses symbols to represent individual language sounds. [17] In contrast, logographic writing systems (such as Chinese) use a symbol to represent an entire word, and syllabic writing systems (such as Japanese kana) use a symbol to represent a single syllable. Alphabetic writing systems vary in complexity. For example, Spanish is an alphabetic writing system that has a nearly perfect one-to-one correspondence of symbols to individual sounds. In Spanish, most of the time words are spelled the way they sound, that is, word spellings are almost always regular. English, on the other hand, is far more complex in that it does not have a one-to-one correspondence between symbols and sounds. English has individual sounds that can be represented by more than one symbol or symbol combination. For example, the long \|a\| sound can be represented by a-consonant-e as in ate, -ay as in hay, -ea as in steak, -ey as in they, -ai as in pain, and -ei as in vein. In addition, there are many words with irregular spelling and many homophones (words that sound the same but have different meanings and often different spellings as well). Pollack Pickeraz (1963) asserted that there are 45 phonemes in the English language, and that the 26 letters of the English alphabet can represent the 45 phonemes in about 350 ways. [18] It should be noted that the irregularity of English spelling is largely an artifact of how the language developed. English is a Germanic language; however, it has substantial influences from Latin, Greek, and French, among others. Over its history, English adopted vocabulary from many languages, and the imported words usually follow the spelling patterns of their language of origin. Advanced phonics instruction includes studying words according to their origin, and how to determine the correct spelling of a word using its language of origin. Clearly, the complexity of English orthography makes it more difficult for children to learn decoding and encoding rules, and more difficult for teachers to teach them. However, effective word recognition relies on the basic understanding that letters represent the sounds of spoken language, that is, word recognition relies on the reader's understanding of the alphabetic principle. ### Phonics Phonics is an instructional technique that teaches readers to attend to the letters or groups of letters that make up words. So, to read the word throat using phonics, each grapheme (a letter or letters that represent one sound) is examined separately: th says /θ/, r says /ɹ/, oa says /oʊ/, and t says /t/. There are various methods for teaching phonics. A common way to teach this is to have the novice reader pronounce each individual sound and "blend" them to pronounce the whole word. This is called synthetic phonics. There are many programs that use this approach. A widely-known program is SRA/McGraw-Hill's DISTAR program (now called Reading Mastery). The Orton-Gillingham method, Lindamood-Bell Phoneme Sequencing Program, and the Wilson reading system are other phonics programs. British educator Nellie Dale is credited with creating one of the earliest programs designed to teach basic reading skills, in the late 19th century.[19] In addition to teaching phonological awareness and sound-symbol correspondence, comprehensive phonics programs also include instruction in irregular words, the 6 syllable types, morphology (root words, prefixes, suffixes, etc) and word origin.[citation needed] ### Whole language Because English spelling has so many irregularities and exceptions, advocates of whole language recommend that novice readers should learn a little about the individual letters in words, especially the consonants and the "short vowels." Teachers provide this knowledge opportunistically, in the context of stories that feature many instances of a particular letter. This is known as "embedded phonics." Children use their letter-sound knowledge in combination with context to read new and difficult words.[20] Programs that use a whole language approach include Reading Recovery and Guided reading.[21] ### Which approach is better? The answer to this question is often debated. Scientific research in reading has tended to support the value of teaching phonics, although reading experts from all perspectives believe that time spent reading--a key element of whole language--is very important. Advocates of whole language have dismissed this scientific research for many different reasons. One common complaint is that scientific education researchers rely on randomized studies (similar in design to those done in medicine) and do not value descriptive research that has demonstrated the value of whole language approaches. In the United States, the National Reading Panel was convened in an attempt to determine which approach was best. It found that phonics was more effective than embedded phonics or no phonics, but it only used experimental and quasi-experimental research (it did not include qualitative research), so the whole language community remained skeptical of its conclusions. The debate continues.[citation needed] Consideration should be given to alternative methods of teaching reading since neither the phonics method, the whole word or whole language method, nor any combination of them is completely successful with every student. See Reading education. ## Why learning to read is hard Many children of average and above average intelligence experience difficulty when learning to read. According to Dr. Grover Whitehurst, Assistant Secretary, U.S. Department of Education, learning to read is difficult for several reasons. First, reading requires the mastery of a code that maps human speech sounds to written symbols, and this code is not readily apparent or easy to understand. Second, reading is not a natural process; it was invented by humans fairly recently in our development. The human brain is wired for spoken language, but it is not wired to process the code of written language. Third, confusion can be introduced at the time of instruction by teachers who do not understand what the code is or how it needs to be taught. [22] One reason that mastery of the code that maps human speech sounds to written symbols is so difficult is that English spelling contains so many irregularities and exceptions to the rules. However, when English spelling rules take into account syllable structure, phonetics, and accents, there are literally dozens of rules that are 75% or more reliable. [23] Some phonics spelling advocates claim that English is more than 80% phonetic.Template:Who This is true is more than one grapheme (letter) is allowed per phoneme; otherwise, English is a little more than 20 percent phonetic. In addition, Dr. Diane McGuinness’ book Why Our Children Can’t Read explains the complex logic that is required to learn to read English. Unlike many alphabetic languages, there are tens of thousands of different syllables in English, with sixteen different syllable patterns in English: (C=consonant, V=vowel) CV, CCV, CCCV, CVC, CCVC, CCCVC, CVCC, CVCCC, CCVCC, CCVCCC, CCCVCCC, CCCVCC, VCCC, VCC, VC, and V. There are two or more syllables in most English words.[24] Each syllable can have one of the sixteen syllable patterns. If each vowel and each consonant in each of these patterns consistently represented the same phoneme (one-to-one mapping), there would be nothing in the logic of these syllables that would be beyond the abilities of most four- or five-year-olds. But they do not. English spelling also has one-to-many and many-to-one mapping. This requires a type of logic that most children do not develop until they are eleven or twelve years old. The types of logic required for one-to-many and many-to-one mapping are: (1) the logic of “classes” (categories where objects or events that are similar are grouped) and “relations” (where objects share some features but not all features, e.g. all poodles are dogs, but not all dogs are poodles) and (2) “propositional logic,” which involves combining both the classes and relations types of logic. This requires the ability to think of the same item in more than one way at the same time. These combinations require the use of relational terms such as “and,” “or,” “not,” “if—then,” and “if and only if” in formal statements of propositional logic, e.g. if an H follows the T, then say /TH/ as in thin or then; but if any other letter or no letter follows the T, then say /T/ as in top or ant.[25] It takes most students learning to read English at least two to two-and-one-half years to learn enough words so that they can read most written material easily enough that they enjoy reading, read often, and thereby become fluent readers.[citation needed] ## Reading comprehension Many educators in the USA believe that children need to learn to analyze text (comprehend it) even before they can read it on their own, and comprehension instruction generally begins in pre-Kindergarten or Kindergarten. But other US educators consider this reading approach to be completely backward for very young children, arguing that the children must learn how to decode the words in a story through phonics before they can analyze the story itself. During the last century comprehension lessons usually comprised students answering teachers' questions, writing responses to questions on their own, or both. The whole group version of this practice also often included "round robin reading," wherein teachers called on individual students to read a portion of the text (and sometimes following a set order). In the last quarter of the 20th century, evidence accumulated that the read-test methods assessed comprehension more than they taught it. The associated practice of "round robin" reading has also been questioned and eliminated by many educators. Instead of using the prior read-test method, research studies have concluded that there are much more effective ways to teach comprehension. Much work has been done in the area of teaching novice readers a bank of "reading strategies," or tools to interpret and analyze text.[26] There is not a definitive set of strategies, but common ones include summarizing what you have read, monitoring your reading to make sure it is still making sense, and analyzing the structure of the text (e.g., the use of headings in science text). Some programs teach students how to self monitor whether they are understanding and provide students with tools for fixing comprehension problems. Instruction in comprehension strategy use often involves the gradual release of responsibility, wherein teachers initially explain and model strategies. Over time, they give students more and more responsibility for using the strategies until they can use them independently. This technique is generally associated with the idea of self-regulation and reflects social cognitive theory, originally conceptualized by Albert Bandura. # Broader and complementary definitions Traditional definitions of literacy consider the ability to "read, write, spell, listen, and speak."[27] Some have argued that the definition of literacy should be expanded. For example, in the United States, the National Council of Teachers of English and the International Reading Association have added "visually representing" to the traditional list of competencies. Similarly, in Scotland, literacy has been defined as: "The ability to read and write and use numeracy, to handle information, to express ideas and opinions, to make decisions and solve problems, as family members, workers, citizens and lifelong learners."[28] A basic literacy standard in many societies is the ability to read the newspaper. Increasingly, communication in commerce or society in general requires the ability to use computers and other digital technologies. [29] Since the 1990s, when the Internet came into wide use in the United States, some have asserted that the definition of literacy should include the ability to use tools such as web browsers, word processing programs, and text messages. Similar expanded skill sets have been called multimedia literacy, computer literacy, information literacy, and technacy.[30] "Arts literacy" programs exist in some places in the United States,[31] Australia, Canada, and Finland.Template:Facts Other genres under study by academia include critical literacy, media literacy, and health literacy[32] Some scholarsTemplate:Weasel-inline argue that literacy necessarily includes the cultural, political, and historical contexts of the community in which communication takes place.[33]	https://www.wikidoc.org/index.php/Literacy
a4e68e714ebb5db3803a56991876d26f46af604a	wikidoc	Litharge	Litharge Litharge is one of the natural mineral forms of lead(II) oxide, PbO. Litharge is a secondary mineral which forms from the oxidation of galena ores. It forms as coatings and encrustations with internal tetragonal crystal structure. It is dimorphous with the orthorhombic form massicot. It forms soft (Mohs hardness of 2), red, greasy-appearing crusts with a very high specific gravity of 9.14–9.35. It was first described as a mineral in 1917 for an occurrence in San Bernardino County, California. Historically, the term "litharge" has been combined to refer to other similar substances. For example, litharge of gold is litharge mixed with red lead, giving it a red color; litharge of silver is litharge that comes as a by-product of separating silver from lead; litharge of bismuth is a similar result of the oxidation of bismuth. The term has also been used as a synonym for white lead or red lead.	Litharge Litharge is one of the natural mineral forms of lead(II) oxide, PbO. Litharge is a secondary mineral which forms from the oxidation of galena ores. It forms as coatings and encrustations with internal tetragonal crystal structure. It is dimorphous with the orthorhombic form massicot. It forms soft (Mohs hardness of 2), red, greasy-appearing crusts with a very high specific gravity of 9.14–9.35. It was first described as a mineral in 1917 for an occurrence in San Bernardino County, California. Historically, the term "litharge" has been combined to refer to other similar substances. For example, litharge of gold is litharge mixed with red lead, giving it a red color; litharge of silver is litharge that comes as a by-product of separating silver from lead; litharge of bismuth is a similar result of the oxidation of bismuth. The term has also been used as a synonym for white lead or red lead.[1]	https://www.wikidoc.org/index.php/Litharge
eb4f199eca12dd4d59307df495c914a3f77460dd	wikidoc	Lo Ovral	Lo Ovral Synonyms / Brand Names: # Dosing and Administration FDA Package Insert Resources Indications, Contraindications, Side Effects, Drug Interactions, etc. Calculate Creatine Clearance On line calculator of your patients Cr Cl by a variety of formulas. Convert pounds to Kilograms On line calculator of your patients weight in pounds to Kg for dosing estimates. Publication Resources Recent articles, WikiDoc State of the Art Review, Textbook Information Trial Resources Ongoing Trials, Trial Results Guidelines & Evidence Based Medicine Resources US National Guidelines, Cochrane Collaboration, etc. Media Resources Slides, Video, Images, MP3, Podcasts, etc. Patient Resources Discussion Groups, Handouts, Blogs, News, etc. International Resources en Español # FDA Package Insert Resources Indications Contraindications Side Effects Drug Interactions Precautions Overdose Instructions for Administration How Supplied Pharmacokinetics and Molecular Data FDA label FDA on Lo Ovral Return to top # Publication Resources Most Recent Articles on Lo Ovral Review Articles on Lo Ovral Articles on Lo Ovral in N Eng J Med, Lancet, BMJ Textbook Information on Lo Ovral Return to top # Trial Resources Ongoing Trials with Lo Ovral at Clinical Trials.gov Trial Results with Lo Ovral Return to top # Guidelines & Evidence Based Medicine Resources US National Guidelines Clearinghouse on Lo Ovral Cochrane Collaboration on Lo Ovral Cost Effectiveness of Lo Ovral Return to top # Media Resources Powerpoint Slides on Lo Ovral Images of Lo Ovral Podcasts & MP3s on Lo Ovral Videos on Lo Ovral Return to top # Patient Resources Patient Resources on Lo Ovral Discussion Groups on Lo Ovral Patient Handouts on Lo Ovral Blogs on Lo Ovral Lo Ovral in the News Lo Ovral in the Marketplace Return to top # International Resources Lo Ovral en Español Return to top Adapted from the FDA Package Insert.	Lo Ovral Synonyms / Brand Names: Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Dosing and Administration FDA Package Insert Resources Indications, Contraindications, Side Effects, Drug Interactions, etc. Calculate Creatine Clearance On line calculator of your patients Cr Cl by a variety of formulas. Convert pounds to Kilograms On line calculator of your patients weight in pounds to Kg for dosing estimates. Publication Resources Recent articles, WikiDoc State of the Art Review, Textbook Information Trial Resources Ongoing Trials, Trial Results Guidelines & Evidence Based Medicine Resources US National Guidelines, Cochrane Collaboration, etc. Media Resources Slides, Video, Images, MP3, Podcasts, etc. Patient Resources Discussion Groups, Handouts, Blogs, News, etc. International Resources en Español # FDA Package Insert Resources Indications Contraindications Side Effects Drug Interactions Precautions Overdose Instructions for Administration How Supplied Pharmacokinetics and Molecular Data FDA label FDA on Lo Ovral Return to top # Publication Resources Most Recent Articles on Lo Ovral Review Articles on Lo Ovral Articles on Lo Ovral in N Eng J Med, Lancet, BMJ Textbook Information on Lo Ovral Return to top # Trial Resources Ongoing Trials with Lo Ovral at Clinical Trials.gov Trial Results with Lo Ovral Return to top # Guidelines & Evidence Based Medicine Resources US National Guidelines Clearinghouse on Lo Ovral Cochrane Collaboration on Lo Ovral Cost Effectiveness of Lo Ovral Return to top # Media Resources Powerpoint Slides on Lo Ovral Images of Lo Ovral Podcasts & MP3s on Lo Ovral Videos on Lo Ovral Return to top # Patient Resources Patient Resources on Lo Ovral Discussion Groups on Lo Ovral Patient Handouts on Lo Ovral Blogs on Lo Ovral Lo Ovral in the News Lo Ovral in the Marketplace Return to top # International Resources Lo Ovral en Español Return to top Adapted from the FDA Package Insert.	https://www.wikidoc.org/index.php/Lo_Ovral
43d8f162d5e064e1e961e254b67421e0715fd8d4	wikidoc	Lobeline	Lobeline # Overview Lobeline is an alkaloid found in "Indian tobacco" (Lobelia inflata), "Devil's tobacco" (Lobelia tupa), "cardinal flower" (Lobelia cardinalis), "great lobelia" (Lobelia siphilitica), and Hippobroma longiflora. Additionally, it is also found in Lobelia chinensis. In its pure form it is a white amorphous powder which is freely soluble in water. # Potential uses Lobeline has been studied for its potential use as a smoking cessation aid, and may have application in the treatment of other drug addictions such as addiction to amphetamines, cocaine, or alcohol. # Pharmacology Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand, which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine. It also inhibits the reuptake of dopamine and serotonin, and acts as a mixed agonist–antagonist at nicotinic acetylcholine receptors to which it binds at the subunit interfaces of the extracellular domain. It is also an antagonist at μ-opioid receptors.	Lobeline Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Lobeline is an alkaloid found in "Indian tobacco" (Lobelia inflata), "Devil's tobacco" (Lobelia tupa), "cardinal flower" (Lobelia cardinalis), "great lobelia" (Lobelia siphilitica), and Hippobroma longiflora. Additionally, it is also found in Lobelia chinensis. In its pure form it is a white amorphous powder which is freely soluble in water. # Potential uses Lobeline has been studied for its potential use as a smoking cessation aid,[1][2][3] and may have application in the treatment of other drug addictions such as addiction to amphetamines,[4][5] cocaine,[6] or alcohol.[7] # Pharmacology Lobeline has multiple mechanisms of action, acting as a VMAT2 ligand,[8][9][10] which stimulates dopamine release to a moderate extent when administered alone, but reduces the dopamine release caused by methamphetamine.[11][12] It also inhibits the reuptake of dopamine and serotonin,[13] and acts as a mixed agonist–antagonist at nicotinic acetylcholine receptors[14][15] to which it binds at the subunit interfaces of the extracellular domain.[16] It is also an antagonist at μ-opioid receptors.[17]	https://www.wikidoc.org/index.php/Lobeline
6532fc3fb4a47dce0e0a6cf18e5600fb12d4e73f	wikidoc	Lomatium	Lomatium Lomatium is a genus of 70 to 80 perennial herbs native to western North America. Several species, including L. cous, L. geyeri, and L. macrocarpum, are sometimes known as biscuit roots for their starchy edible roots. These are or have been traditional Native American foods, eaten cooked or dried and ground into flour. Their flavor has been compared to celery, parsnip, or stale biscuits. The roots of some species, including L. dissectum, have been used as herbal medicines for cough and upper respiratory infections. The University of British Columbia has performed research showing that extract of L. dissectum is effective at imobilizing the tuberculosis and avium mycobacterium in the laboratory, but efficacy on human beings has not been tested. This plant family is well know for members that are highly toxic. # Selected species - L. ambiguum - L. bicolor - L. bradshawii - L. brandegei - L. californicum - L. canbyi - L. columbianum - L. cous - L. cusickii - L. cuspidatum - L. dissectum - L. donnellii - L. farinosum - L. foeniculaceum - L. geyeri - L. gormanii - L. grayi - L. greenmanii - L. hallii - L. hambleniae - L. hendersonii - L. idahoense - L. laevigatum - L. leptocarpum - L. macrocarpum - L. martindalei - L. minus - L. nevadense - L. nudicaule - L. oreganum - L. orogenioides - L. rollinsii - L. roseanum - L. salmoniflorum - L. serpentinum - L. suksdorfii - L. thompsonii - L. triternatum - L. tuberosum - L. utriculatum - L. vaginatum - L. watsonii	Lomatium Lomatium is a genus of 70 to 80 perennial herbs native to western North America. Several species, including L. cous, L. geyeri, and L. macrocarpum, are sometimes known as biscuit roots for their starchy edible roots. These are or have been traditional Native American foods, eaten cooked or dried and ground into flour. Their flavor has been compared to celery, parsnip, or stale biscuits. The roots of some species, including L. dissectum, have been used as herbal medicines for cough and upper respiratory infections. The University of British Columbia has performed research showing that extract of L. dissectum is effective at imobilizing the tuberculosis and avium mycobacterium in the laboratory, but efficacy on human beings has not been tested. This plant family is well know for members that are highly toxic. # Selected species - L. ambiguum - L. bicolor - L. bradshawii - L. brandegei - L. californicum - L. canbyi - L. columbianum - L. cous - L. cusickii - L. cuspidatum - L. dissectum - L. donnellii - L. farinosum - L. foeniculaceum - L. geyeri - L. gormanii - L. grayi - L. greenmanii - L. hallii - L. hambleniae - L. hendersonii - L. idahoense - L. laevigatum - L. leptocarpum - L. macrocarpum - L. martindalei - L. minus - L. nevadense - L. nudicaule - L. oreganum - L. orogenioides - L. rollinsii - L. roseanum - L. salmoniflorum - L. serpentinum - L. suksdorfii - L. thompsonii - L. triternatum - L. tuberosum - L. utriculatum - L. vaginatum - L. watsonii # External links - UVSC Herbarium - Lomatium - Food uses at Plants for a Future - Descriptions and photographs of several species Template:Asterid-stub	https://www.wikidoc.org/index.php/Lomatium
98b88cf8d8c3bc43eb445205de1c43320ae5ff4a	wikidoc	Probucol	Probucol # Overview Probucol is an anti-hyperlipidemic drug initially developed in the treatment of coronary artery disease. However, clinical trials were stopped after it was found that it may lower HDL in patients with a previous history of heart disease. Probucol was initially developed in the 1970s by a chemical company to maximize airplane tire longevity. Probucol is associated with QT interval prolongation. # Mechanism Probucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption. Probucol is a powerful antioxidant which inhibits the oxidation of cholesterol in LDLs; this slows the formation of foam cells, which contribute to atherosclerotic plaques. It is believed to act at ABCA1. It also lowers levels of HDL.	Probucol Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] # Overview Probucol is an anti-hyperlipidemic drug[1] initially developed in the treatment of coronary artery disease. However, clinical trials were stopped after it was found that it may lower HDL in patients with a previous history of heart disease. Probucol was initially developed in the 1970s by a chemical company to maximize airplane tire longevity. Probucol is associated with QT interval prolongation. # Mechanism Probucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption.[2] Probucol is a powerful antioxidant which inhibits the oxidation of cholesterol in LDLs; this slows the formation of foam cells, which contribute to atherosclerotic plaques. It is believed to act at ABCA1.[3] It also lowers levels of HDL.[4]	https://www.wikidoc.org/index.php/Lorelco
c55f1a897705759b1705014ed5d1db28485d426d	wikidoc	Loricrin	Loricrin Loricrin is a protein that in humans is encoded by the LOR gene. # Function Loricrin is a major protein component of the cornified cell envelope found in terminally differentiated epidermal cells. Loricrin is expressed in the granular layer of all keratinized epithelial cells of mammals tested including oral, esophageal and stomach mucosa of rodents, tracheal squamous metaplasia of vitamin A deficient hamster and estrogen induced squamous vaginal epithelium of rats. # Clinical significance Mutations in the LOR gene are associated with Vohwinkel's syndrome and Camisa disease, both inherited skin diseases.	Loricrin Loricrin is a protein that in humans is encoded by the LOR gene.[1][2][3] # Function Loricrin is a major protein component of the cornified cell envelope found in terminally differentiated epidermal cells.[3] Loricrin is expressed in the granular layer of all keratinized epithelial cells of mammals tested including oral, esophageal and stomach mucosa of rodents, tracheal squamous metaplasia of vitamin A deficient hamster and estrogen induced squamous vaginal epithelium of rats.[4] # Clinical significance Mutations in the LOR gene are associated with Vohwinkel's syndrome and Camisa disease, both inherited skin diseases.	https://www.wikidoc.org/index.php/Loricrin
1f6f21923d268b415e2ac8127666b285fa1dbd49	wikidoc	Lundbeck	Lundbeck H. Lundbeck A/S (Template:OMX) (also known as Lundbeck) is a Danish international pharmaceutical company engaged in the research and development, production, marketing and sale of drugs for the treatment of psychiatric and neurological disorders. The company was founded by Hans Lundbeck in 1915, and was initially a trading company supplying a variety of goods to the Danish market, including machinery for manufacturing, aluminium foil, artificial sweeteners and photographic equipment. Lundbeck entered the pharmaceutical market in 1924, importing medicines and cosmetics from companies based in other European and American countries. By the late 1930s, Lundbeck had begun to produce its own medicinal products and had established its own research department. Production continued (although limited due to a lack of raw materials) during the Second World War. After the war, Lundbeck continued to grow, and became a major international pharmaceutical company focusing on the production of drugs used to treat disorders and diseases of the central nervous system. In 2007, the company's revenue was €1.47 billion. Key products are the selective serotonin reuptake inhibitor escitalopram, and memantine.	Lundbeck Template:Infobox Company H. Lundbeck A/S (Template:OMX) (also known as Lundbeck) is a Danish international pharmaceutical company engaged in the research and development, production, marketing and sale of drugs for the treatment of psychiatric and neurological disorders. The company was founded by Hans Lundbeck in 1915, and was initially a trading company supplying a variety of goods to the Danish market, including machinery for manufacturing, aluminium foil, artificial sweeteners and photographic equipment. Lundbeck entered the pharmaceutical market in 1924, importing medicines and cosmetics from companies based in other European and American countries. By the late 1930s, Lundbeck had begun to produce its own medicinal products and had established its own research department. Production continued (although limited due to a lack of raw materials) during the Second World War. After the war, Lundbeck continued to grow, and became a major international pharmaceutical company focusing on the production of drugs used to treat disorders and diseases of the central nervous system. In 2007, the company's revenue was €1.47 billion. Key products are the selective serotonin reuptake inhibitor escitalopram, and memantine.	https://www.wikidoc.org/index.php/Lundbeck
0e3bda792f06abd2fc1f976a5f1f25f45dbe085d	wikidoc	Lycopene	Lycopene Lycopene is a bright red carotenoid pigment, a phytochemical found in tomatoes and other red fruits. Lycopene is the most common carotenoid in the human body and is one of the most potent carotenoid antioxidants. Its name is derived from the tomato's species classification, Solanum lycopersicum (formerly Lycopersicon esculentum). # Structure and chemistry Lycopene is a terpene assembled from 8 isoprene units. The color of lycopene is due to its many conjugated carbon double bonds. Each double bond reduces the energy required for electrons to transition to higher energy states, allowing the molecule to absorb visible light of progressively longer wavelengths. Lycopene absorbs most of the visible spectrum, so it appears red. If lycopene is oxidized (for example, by reacting with bleaches or acids), the double bonds between carbon atoms will be broken, cleaving the molecule into smaller molecules each double-bonded to an oxygen atom. Although C=O bonds are also chromophoric, the much shorter molecules are unable to absorb enough light to appear colorful. A similar effect occurs if lycopene is reduced; reduction may saturate (convert the double bonds to single bonds) the lycopene molecule, diminishing its ability to absorb light. # Dietary sources Fruits and vegetables that are high in lycopene include tomatoes, watermelon, pink grapefruit, pink guava, papaya, gac, and rosehip. Unlike other fruits and vegetables, where nutritional content such as vitamin C is diminished upon cooking, processing of tomatoes increases the concentration of bioavailable lycopene. Lycopene in tomato paste is four times more bioavailable than in fresh tomatoes. This is because lycopene is so insoluble in water and is so tightly bound to vegetable fiber. Thus processed tomato products such as pasteurized tomato juice, soup, sauce, and ketchup contain the highest concentrations of bioavailable lycopene. Cooking and crushing tomatoes (as in the canning process) and serving in oil-rich dishes (such as spaghetti sauce or pizza) greatly increases assimilation from the digestive tract into the bloodstream. Lycopene is fat-soluble, so the oil is said to help absorption. # Production Lycopene may be obtained from vegetables and fruits such as the tomato, but another source of lycopene is the fungus Blakeslea trispora. # Nutritional benefits Lycopene is the most powerful carotenoid quencher of singlet oxygen, being 100 times more efficient in the singlet-oxygen quenching action than Vitamin E, which in turn has 125 times the quenching action of glutathione (water soluble). Singlet oxygen produced during exposure to ultraviolet light is a primary cause of skin aging. Given its antioxidant properties, some scientific research has investigated the correlation between lycopene consumption and general health. Early research suggested some amelioration of cardiovascular disease, cancer, diabetes, osteoporosis, and even male infertility. . The most recent study, however, has cast significant doubt on these benefits, showing no link between lycopene and cancer prevention. In fact, a related antioxidant, beta-carotene, was shown to increase the number of prostate cancer cases. # Food coloring Due to its ubiquity, lycopene has been licensed for use as a food coloring. Lycopene is not water-soluble and instantly stains any sufficiently porous material, including most plastics. While a tomato stain can be fairly easily removed from fabric (provided the stain is fresh), lycopene diffuses into plastic, making it impossible to remove with hot water, soap, or detergent. (Bleach will destroy lycopene, however.) Plastics are especially susceptible to staining if heated, scratched, oiled, or pitted, for example by acids. # Formulations Available Lycopene is available in the market as mix formulation with some other carotinoids and antioxidants. It is marketed by a number of pharmaceutical companies under different brand names. Some commonly available formulations are LYCORED, LYNET, LYCORICH etc.	Lycopene Template:Chembox new Lycopene is a bright red carotenoid pigment, a phytochemical found in tomatoes and other red fruits. Lycopene is the most common carotenoid in the human body and is one of the most potent carotenoid antioxidants. Its name is derived from the tomato's species classification, Solanum lycopersicum (formerly Lycopersicon esculentum). # Structure and chemistry Lycopene is a terpene assembled from 8 isoprene units. The color of lycopene is due to its many conjugated carbon double bonds. Each double bond reduces the energy required for electrons to transition to higher energy states, allowing the molecule to absorb visible light of progressively longer wavelengths. Lycopene absorbs most of the visible spectrum, so it appears red. If lycopene is oxidized (for example, by reacting with bleaches or acids), the double bonds between carbon atoms will be broken, cleaving the molecule into smaller molecules each double-bonded to an oxygen atom. Although C=O bonds are also chromophoric, the much shorter molecules are unable to absorb enough light to appear colorful. A similar effect occurs if lycopene is reduced; reduction may saturate (convert the double bonds to single bonds) the lycopene molecule, diminishing its ability to absorb light. # Dietary sources Fruits and vegetables that are high in lycopene include tomatoes, watermelon, pink grapefruit, pink guava, papaya, gac, and rosehip. Unlike other fruits and vegetables, where nutritional content such as vitamin C is diminished upon cooking, processing of tomatoes increases the concentration of bioavailable lycopene. Lycopene in tomato paste is four times more bioavailable than in fresh tomatoes. This is because lycopene is so insoluble in water and is so tightly bound to vegetable fiber. Thus processed tomato products such as pasteurized tomato juice, soup, sauce, and ketchup contain the highest concentrations of bioavailable lycopene. Cooking and crushing tomatoes (as in the canning process) and serving in oil-rich dishes (such as spaghetti sauce or pizza) greatly increases assimilation from the digestive tract into the bloodstream. Lycopene is fat-soluble, so the oil is said to help absorption. # Production Lycopene may be obtained from vegetables and fruits such as the tomato, but another source of lycopene is the fungus Blakeslea trispora. # Nutritional benefits Lycopene is the most powerful carotenoid quencher of singlet oxygen[1], being 100 times more efficient in the singlet-oxygen quenching action than Vitamin E, which in turn has 125 times the quenching action of glutathione (water soluble). Singlet oxygen produced during exposure to ultraviolet light is a primary cause of skin aging.[2] Given its antioxidant properties, some scientific research has investigated the correlation between lycopene consumption and general health. Early research suggested some amelioration of cardiovascular disease, cancer, diabetes, osteoporosis, and even male infertility.[3] [4][5]. The most recent study, however, has cast significant doubt on these benefits, showing no link between lycopene and cancer prevention. In fact, a related antioxidant, beta-carotene, was shown to increase the number of prostate cancer cases[6]. # Food coloring Due to its ubiquity, lycopene has been licensed for use as a food coloring. Lycopene is not water-soluble and instantly stains any sufficiently porous material, including most plastics. While a tomato stain can be fairly easily removed from fabric (provided the stain is fresh), lycopene diffuses into plastic, making it impossible to remove with hot water, soap, or detergent. (Bleach will destroy lycopene, however.) Plastics are especially susceptible to staining if heated, scratched, oiled, or pitted, for example by acids. # Formulations Available Lycopene is available in the market as mix formulation with some other carotinoids and antioxidants. It is marketed by a number of pharmaceutical companies under different brand names. Some commonly available formulations are LYCORED, LYNET, LYCORICH etc.	https://www.wikidoc.org/index.php/Lycopene
38f8b8c9c6bb028f2413e579199287a9525636e8	wikidoc	Lying-in	Lying-in Lying-in is an old childbirth practice involving a woman resting in bed for a period of time before giving birth. Though the term is now usually defined as "the condition of a woman in the process of giving birth," it previously referred to a period of bed rest required even if there was no medical complications. A 1932 publication refers to lying-in as ranging from 2 weeks to 2 months. It also does not suggest "Getting Up" (getting out of bed post-birth) for at least nine days and ideally for 20 days. This prolonged time of staying in bed after birth may also be called "lying-in". When lying-in was a more common term, it was used in the names of several hospitals. For example, the Royal Women’s Hospital in Australia was originally known as the "Melbourne Lying-In Hospital and Infirmary for Diseases of Women and Children".	Lying-in Lying-in is an old childbirth practice involving a woman resting in bed for a period of time before giving birth. Though the term is now usually defined as "the condition of a woman in the process of giving birth," it previously referred to a period of bed rest required even if there was no medical complications. A 1932 publication refers to lying-in as ranging from 2 weeks to 2 months[1]. It also does not suggest "Getting Up" (getting out of bed post-birth) for at least nine days and ideally for 20 days.[1] This prolonged time of staying in bed after birth may also be called "lying-in".[2][3] When lying-in was a more common term, it was used in the names of several hospitals. For example, the Royal Women’s Hospital in Australia was originally known as the "Melbourne Lying-In Hospital and Infirmary for Diseases of Women and Children".[4]	https://www.wikidoc.org/index.php/Lying-in
e9e34732d0a92697ccf7efb3231a3852ccefd7d6	wikidoc	Mitotane	Mitotane # 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 Mitotane is a antineoplastic Agent that is FDA approved for the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. There is a Black Box Warning for this drug as shown here. Common adverse reactions include anorexia, nausea or vomiting, somnolence, Skin toxicity. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) ### Indications - LYSODREN is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. ### Dosage - The recommended treatment schedule is to start the patient at 2 g to 6 g of LYSODREN per day in divided doses, either 3 or 4 times a day. Doses are usually increased incrementally to 9 g to 10 g per day. If severe side effects appear, the dose should be reduced until the maximum tolerated dose is achieved. If the patient can tolerate higher doses and improved clinical response appears possible, the dose should be increased until adverse reactions interfere. Experience has shown that the maximum tolerated dose (MTD) will vary from 2 g to 16 g per day, but has usually been 9 g to 10 g per day. The highest doses used in the studies to date were 18 g to 19 g per day. - Treatment should be instituted in the hospital until a stable dosage regimen is achieved. - Treatment should be continued as long as clinical benefits are observed. Maintenance of clinical status or slowing of growth of metastatic lesions can be considered clinical benefits if they can clearly be shown to have occurred. - If no clinical benefits are observed after 3 months at the maximum tolerated dose, the case would generally be considered a clinical failure. However, 10% of the patients who showed a measurable response required more than 3 months at the MTD. Early diagnosis and prompt institution of treatment improve the probability of a positive clinical response. Clinical effectiveness can be shown by reduction in tumor mass; reduction in pain, weakness or anorexia; and reduction of symptoms and signs due to excessive steroid production. - A number of patients have been treated intermittently with treatment being restarted when severe symptoms have reappeared. Patients often do not respond after the third or fourth such course. Experience accumulated to date suggests that continuous treatment with the maximum possible dosage of LYSODREN is the best approach. - Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1 - To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing LYSODREN tablets. LYSODREN tablets should not be crushed. Personnel should avoid exposure to crushed and/or broken tablets. If contact with broken tablets occurs, wash immediately and thoroughly. More information is available in the references listed below. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mitotane in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mitotane in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding FDA-Labeled Use of Mitotane in pediatric patients. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mitotane in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mitotane in pediatric patients. # Contraindications - LYSODREN (mitotane tablets, USP) should not be given to individuals who have demonstrated a previous hypersensitivity to it. # Warnings - LYSODREN should be temporarily discontinued immediately following shock or severe trauma, since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids. - LYSODREN should be administered with care to patients with liver disease other than metastatic lesions from the adrenal cortex, since the metabolism of LYSODREN may be interfered with and the drug may accumulate. - All possible tumor tissues should be surgically removed from large metastatic masses before LYSODREN administration is instituted. This is necessary to minimize the possibility of infarction and hemorrhage in the tumor due to a rapid cytotoxic effect of the drug. - Long-term continuous administration of high doses of LYSODREN may lead to brain damage and impairment of function. Behavioral and neurological assessments should be made at regular intervals, since toxicity may be reversible after discontinuation of LYSODREN. Literature reports suggest that mitotane plasma concentrations exceeding 20 mcg/mL are associated with a greater incidence of high grade central nervous system toxicity. - A substantial percentage of the patients treated show signs of adrenal insufficiency. It therefore appears necessary to watch for and institute steroid replacement in those patients. However, some investigators have recommended that steroid replacement therapy be administered concomitantly with LYSODREN. It has been shown that the metabolism of exogenous steroids is modified and consequently somewhat higher doses than normal replacement therapy may be required. Since LYSODREN increases hormone binding proteins, measurement of free cortisol and corticotropin (ACTH) levels may be useful in achieving optimal steroid replacement. ### Precautions - Adrenal insufficiency may develop in patients treated with LYSODREN, and adrenal steroid replacement should be considered for these patients. - Since sedation, lethargy, vertigo, and other CNS side effects can occur, ambulatory patients should be cautioned about driving, operating machinery, and other hazardous pursuits requiring mental and physical alertness. - Prolonged bleeding time has been reported in patients treated with LYSODREN. Consider this possibility prior to any surgical intervention. # Adverse Reactions ## Clinical Trials Experience - A very high percentage of patients treated with LYSODREN have shown at least one type of side effect. The main types of adverse reactions consist of the following: - Gastrointestinal disturbances, which consist of anorexia, nausea or vomiting, and in some cases diarrhea, occur in about 80% of the patients. Central nervous system side effects occur in 40% of the patients. These consist primarily of depression as manifested by lethargy and somnolence (25%), and dizziness or vertigo (15%). - Skin toxicity has been observed in about 15% of the cases. These skin changes consist primarily of transient skin rashes which do not seem to be dose related. In some instances, this side effect subsided while the patients were maintained on the drug without a change of dose. - Infrequently occurring side effects involve the eye (visual blurring, diplopia, lens opacity, toxic retinopathy); the genitourinary system (hematuria, hemorrhagic cystitis, and albuminuria); cardiovascular system (hypertension, orthostatic hypotension, and flushing); and some miscellaneous effects including generalized aching, hyperpyrexia, and lowered protein bound iodine (PBI). - The following additional adverse reactions have been identified during postapproval use of LYSODREN. Because reports are voluntary from a population of unknown size, an estimate of frequency cannot be made. - Blood and lymphatic system disorders: neutropenia - Endocrine disorders: growth retardation, hypothyroidism - Psychiatric disorders: confusional state - Nervous system disorders: neuropsychological disturbance, dysarthria, headache, ataxia, mental impairment - Eye disorders: maculopathy - Hepatobiliary disorders: hepatitis, elevation of liver enzymes - Reproductive system and breast disorders: gynecomastia - General disorders and administration site conditions: asthenia - Investigations: blood uric acid decreased, blood cholesterol increased, blood triglycerides increased ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Mitotane in the drug label. # Drug Interactions - LYSODREN is a strong inducer of cytochrome P-450 3A4 (CYP3A4). Monitor patients for a change in dosage requirements for the concomitant drug when administering LYSODREN to patients receiving drugs that are substrates of CYP3A4. - LYSODREN’s CYP induction effect leads to an increase in dosage requirements for warfarin. Closely monitor patients for a change in anticoagulant dosage requirements when administering LYSODREN to patients receiving coumarin-type anticoagulants. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): D - LYSODREN can cause fetal harm when administered to a pregnant woman. Abnormal pregnancy outcomes such as preterm births and early pregnancy loss have been reported in patients exposed to mitotane during pregnancy. Animal reproduction studies have not been conducted with LYSODREN. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. - Advise women of childbearing potential to use effective contraception during treatment and after discontinuation of treatment for as long as mitotane plasma levels are detectable Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mitotane in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mitotane during labor and delivery. ### Nursing Mothers - Mitotane has been detected in breast milk. Because of the potential for serious adverse reactions in nursing infants from mitotane, advise women to discontinue nursing during LYSODREN therapy and after treatment discontinuation for as long as mitotane plasma levels are detectable ### Pediatric Use - Safety and effectiveness in pediatric patients have not been established. ### Geriatic Use - Clinical studies of LYSODREN did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between 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. ### Gender There is no FDA guidance on the use of Mitotane with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mitotane with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mitotane in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mitotane in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mitotane in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mitotane in patients who are immunocompromised. # Administration and Monitoring ### Administration - Oral ### Monitoring - Long-term continuous administration of high doses of LYSODREN may lead to brain damage and impairment of function. Behavioral and neurological assessments should be made at regular intervals, since toxicity may be reversible after discontinuation of LYSODREN. # IV Compatibility There is limited information regarding IV Compatibility of Mitotane in the drug label. # Overdosage - No proven antidotes have been established for LYSODREN overdosage. The long half-life of mitotane will require prolonged observation for toxicity # Pharmacology ## Mechanism of Action - LYSODREN can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. Its biochemical mechanism of action is unknown. Data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex. The administration of LYSODREN alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-β-hydroxycortisol. ## Structure - LYSODREN® (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p′-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below: - LYSODREN is a white granular solid composed of clear colorless crystals. It is tasteless and has a slight pleasant aromatic odor. It is soluble in ethanol, isooctane, and carbon tetrachloride. It has a molecular weight of 320.05. - Inactive ingredients in LYSODREN tablets are: avicel, Polyethylene Glycol 3350, silicon dioxide, and starch. - LYSODREN is available as 500 mg scored tablets for oral administration. ## Pharmacodynamics There is limited information regarding Pharmacodynamics of Mitotane in the drug label. ## Pharmacokinetics - Data in adrenal carcinoma patients indicate that about 40% of oral LYSODREN is absorbed and approximately 10% of the administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues. - Following discontinuation of LYSODREN, the plasma terminal half-life has ranged from 18 to 159 days. In most patients blood levels become undetectable after 6 to 9 weeks. Autopsy data have provided evidence that LYSODREN is found in most tissues of the body; however, fat tissues are the primary site of storage. LYSODREN is converted to a water-soluble metabolite. - No unchanged LYSODREN has been found in urine or bile. ## Nonclinical Toxicology - The carcinogenic and mutagenic potentials of LYSODREN (mitotane tablets, USP) are unknown. However, the mechanism of action of this compound suggests that it probably has less carcinogenic potential than other cytotoxic chemotherapeutic drugs. # Clinical Studies There is limited information regarding Clinical Studies of Mitotane in the drug label. # How Supplied - LYSODREN® (mitotane tablets, USP) NDC 0015-3080-60—500 mg Tablets, bottle of 100 ## 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 See How Supplied section for a complete list of available packages of LYSODREN. NDC 0015-3080-60 100 TABLETS LYSODREN® (mitotane tablets, USP) EACH TABLET CONTAINS 500 mg Rx only Bristol-Myers Squibb ### Ingredients and Appearance # Patient Counseling Information There is limited information regarding Patient Counseling Information of Mitotane in the drug label. # Precautions with Alcohol - Alcohol-Mitotane interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Lysodren® # Look-Alike Drug Names There is limited information regarding Mitotane Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	Mitotane Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2] # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. # Black Box Warning # Overview Mitotane is a antineoplastic Agent that is FDA approved for the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. There is a Black Box Warning for this drug as shown here. Common adverse reactions include anorexia, nausea or vomiting, somnolence, Skin toxicity. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) ### Indications - LYSODREN is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. ### Dosage - The recommended treatment schedule is to start the patient at 2 g to 6 g of LYSODREN per day in divided doses, either 3 or 4 times a day. Doses are usually increased incrementally to 9 g to 10 g per day. If severe side effects appear, the dose should be reduced until the maximum tolerated dose is achieved. If the patient can tolerate higher doses and improved clinical response appears possible, the dose should be increased until adverse reactions interfere. Experience has shown that the maximum tolerated dose (MTD) will vary from 2 g to 16 g per day, but has usually been 9 g to 10 g per day. The highest doses used in the studies to date were 18 g to 19 g per day. - Treatment should be instituted in the hospital until a stable dosage regimen is achieved. - Treatment should be continued as long as clinical benefits are observed. Maintenance of clinical status or slowing of growth of metastatic lesions can be considered clinical benefits if they can clearly be shown to have occurred. - If no clinical benefits are observed after 3 months at the maximum tolerated dose, the case would generally be considered a clinical failure. However, 10% of the patients who showed a measurable response required more than 3 months at the MTD. Early diagnosis and prompt institution of treatment improve the probability of a positive clinical response. Clinical effectiveness can be shown by reduction in tumor mass; reduction in pain, weakness or anorexia; and reduction of symptoms and signs due to excessive steroid production. - A number of patients have been treated intermittently with treatment being restarted when severe symptoms have reappeared. Patients often do not respond after the third or fourth such course. Experience accumulated to date suggests that continuous treatment with the maximum possible dosage of LYSODREN is the best approach. - Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1 - To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing LYSODREN tablets. LYSODREN tablets should not be crushed. Personnel should avoid exposure to crushed and/or broken tablets. If contact with broken tablets occurs, wash immediately and thoroughly. More information is available in the references listed below. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mitotane in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mitotane in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding FDA-Labeled Use of Mitotane in pediatric patients. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mitotane in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mitotane in pediatric patients. # Contraindications - LYSODREN (mitotane tablets, USP) should not be given to individuals who have demonstrated a previous hypersensitivity to it. # Warnings - LYSODREN should be temporarily discontinued immediately following shock or severe trauma, since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids. - LYSODREN should be administered with care to patients with liver disease other than metastatic lesions from the adrenal cortex, since the metabolism of LYSODREN may be interfered with and the drug may accumulate. - All possible tumor tissues should be surgically removed from large metastatic masses before LYSODREN administration is instituted. This is necessary to minimize the possibility of infarction and hemorrhage in the tumor due to a rapid cytotoxic effect of the drug. - Long-term continuous administration of high doses of LYSODREN may lead to brain damage and impairment of function. Behavioral and neurological assessments should be made at regular intervals, since toxicity may be reversible after discontinuation of LYSODREN. Literature reports suggest that mitotane plasma concentrations exceeding 20 mcg/mL are associated with a greater incidence of high grade central nervous system toxicity. - A substantial percentage of the patients treated show signs of adrenal insufficiency. It therefore appears necessary to watch for and institute steroid replacement in those patients. However, some investigators have recommended that steroid replacement therapy be administered concomitantly with LYSODREN. It has been shown that the metabolism of exogenous steroids is modified and consequently somewhat higher doses than normal replacement therapy may be required. Since LYSODREN increases hormone binding proteins, measurement of free cortisol and corticotropin (ACTH) levels may be useful in achieving optimal steroid replacement. ### Precautions - Adrenal insufficiency may develop in patients treated with LYSODREN, and adrenal steroid replacement should be considered for these patients. - Since sedation, lethargy, vertigo, and other CNS side effects can occur, ambulatory patients should be cautioned about driving, operating machinery, and other hazardous pursuits requiring mental and physical alertness. - Prolonged bleeding time has been reported in patients treated with LYSODREN. Consider this possibility prior to any surgical intervention. # Adverse Reactions ## Clinical Trials Experience - A very high percentage of patients treated with LYSODREN have shown at least one type of side effect. The main types of adverse reactions consist of the following: - Gastrointestinal disturbances, which consist of anorexia, nausea or vomiting, and in some cases diarrhea, occur in about 80% of the patients. Central nervous system side effects occur in 40% of the patients. These consist primarily of depression as manifested by lethargy and somnolence (25%), and dizziness or vertigo (15%). - Skin toxicity has been observed in about 15% of the cases. These skin changes consist primarily of transient skin rashes which do not seem to be dose related. In some instances, this side effect subsided while the patients were maintained on the drug without a change of dose. - Infrequently occurring side effects involve the eye (visual blurring, diplopia, lens opacity, toxic retinopathy); the genitourinary system (hematuria, hemorrhagic cystitis, and albuminuria); cardiovascular system (hypertension, orthostatic hypotension, and flushing); and some miscellaneous effects including generalized aching, hyperpyrexia, and lowered protein bound iodine (PBI). - The following additional adverse reactions have been identified during postapproval use of LYSODREN. Because reports are voluntary from a population of unknown size, an estimate of frequency cannot be made. - Blood and lymphatic system disorders: neutropenia - Endocrine disorders: growth retardation, hypothyroidism - Psychiatric disorders: confusional state - Nervous system disorders: neuropsychological disturbance, dysarthria, headache, ataxia, mental impairment - Eye disorders: maculopathy - Hepatobiliary disorders: hepatitis, elevation of liver enzymes - Reproductive system and breast disorders: gynecomastia - General disorders and administration site conditions: asthenia - Investigations: blood uric acid decreased, blood cholesterol increased, blood triglycerides increased ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Mitotane in the drug label. # Drug Interactions - LYSODREN is a strong inducer of cytochrome P-450 3A4 (CYP3A4). Monitor patients for a change in dosage requirements for the concomitant drug when administering LYSODREN to patients receiving drugs that are substrates of CYP3A4. - LYSODREN’s CYP induction effect leads to an increase in dosage requirements for warfarin. Closely monitor patients for a change in anticoagulant dosage requirements when administering LYSODREN to patients receiving coumarin-type anticoagulants. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): D - LYSODREN can cause fetal harm when administered to a pregnant woman. Abnormal pregnancy outcomes such as preterm births and early pregnancy loss have been reported in patients exposed to mitotane during pregnancy. Animal reproduction studies have not been conducted with LYSODREN. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. - Advise women of childbearing potential to use effective contraception during treatment and after discontinuation of treatment for as long as mitotane plasma levels are detectable Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mitotane in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mitotane during labor and delivery. ### Nursing Mothers - Mitotane has been detected in breast milk. Because of the potential for serious adverse reactions in nursing infants from mitotane, advise women to discontinue nursing during LYSODREN therapy and after treatment discontinuation for as long as mitotane plasma levels are detectable ### Pediatric Use - Safety and effectiveness in pediatric patients have not been established. ### Geriatic Use - Clinical studies of LYSODREN did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between 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. ### Gender There is no FDA guidance on the use of Mitotane with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mitotane with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mitotane in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mitotane in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mitotane in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mitotane in patients who are immunocompromised. # Administration and Monitoring ### Administration - Oral ### Monitoring - Long-term continuous administration of high doses of LYSODREN may lead to brain damage and impairment of function. Behavioral and neurological assessments should be made at regular intervals, since toxicity may be reversible after discontinuation of LYSODREN. # IV Compatibility There is limited information regarding IV Compatibility of Mitotane in the drug label. # Overdosage - No proven antidotes have been established for LYSODREN overdosage. The long half-life of mitotane will require prolonged observation for toxicity # Pharmacology ## Mechanism of Action - LYSODREN can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. Its biochemical mechanism of action is unknown. Data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex. The administration of LYSODREN alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-β-hydroxycortisol. ## Structure - LYSODREN® (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p′-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below: - LYSODREN is a white granular solid composed of clear colorless crystals. It is tasteless and has a slight pleasant aromatic odor. It is soluble in ethanol, isooctane, and carbon tetrachloride. It has a molecular weight of 320.05. - Inactive ingredients in LYSODREN tablets are: avicel, Polyethylene Glycol 3350, silicon dioxide, and starch. - LYSODREN is available as 500 mg scored tablets for oral administration. ## Pharmacodynamics There is limited information regarding Pharmacodynamics of Mitotane in the drug label. ## Pharmacokinetics - Data in adrenal carcinoma patients indicate that about 40% of oral LYSODREN is absorbed and approximately 10% of the administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues. - Following discontinuation of LYSODREN, the plasma terminal half-life has ranged from 18 to 159 days. In most patients blood levels become undetectable after 6 to 9 weeks. Autopsy data have provided evidence that LYSODREN is found in most tissues of the body; however, fat tissues are the primary site of storage. LYSODREN is converted to a water-soluble metabolite. - No unchanged LYSODREN has been found in urine or bile. ## Nonclinical Toxicology - The carcinogenic and mutagenic potentials of LYSODREN (mitotane tablets, USP) are unknown. However, the mechanism of action of this compound suggests that it probably has less carcinogenic potential than other cytotoxic chemotherapeutic drugs. # Clinical Studies There is limited information regarding Clinical Studies of Mitotane in the drug label. # How Supplied - LYSODREN® (mitotane tablets, USP) NDC 0015-3080-60—500 mg Tablets, bottle of 100 ## 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 See How Supplied section for a complete list of available packages of LYSODREN. NDC 0015-3080-60 100 TABLETS LYSODREN® (mitotane tablets, USP) EACH TABLET CONTAINS 500 mg Rx only Bristol-Myers Squibb ### Ingredients and Appearance # Patient Counseling Information There is limited information regarding Patient Counseling Information of Mitotane in the drug label. # Precautions with Alcohol - Alcohol-Mitotane interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Lysodren®[1] # Look-Alike Drug Names There is limited information regarding Mitotane Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	https://www.wikidoc.org/index.php/Lysodren
074ba6a2250ec8f899bd7ec9e41c7263e6ad6900	wikidoc	Lysosome	Lysosome # Overview Lysosomes are organelles that contain digestive enzymes (acid hydrolases). They digest excess or worn out organelles, food particles, and engulfed viruses or bacteria. The membrane surrounding a lysosome prevents the digestive enzymes inside from destroying the cell. Lysosomes fuse with vacuoles and dispense their enzymes into the vacuoles, digesting their contents. They are built in the Golgi apparatus. The name lysosome derives from the Greek words lysis, which means dissolution or destruction, and soma, which means body. They are frequently nicknamed "suicide-bags" or "suicide-sacs" by cell biologists due to their role in autolysis. Lysosomes were discovered by the Belgian cytologist Christian de Duve in 1949. # Acidic environment At pH 4.8, the interior of the lysosomes is more acidic than the cytosol (pH 7.2). The lysosome single membrane stabilizes the low pH by pumping in protons (H+) from the cytosol via proton pumps and chloride ion channels. The membrane also protects the cytosol, and therefore the rest of the cell, from the degradative enzymes within the lysosome. For this reason, should a lysosome's acid hydrolases leak into the cytosol, their potential to damage the cell will be reduced, because they will not be at their optimum pH! # Enzymes Some important enzymes in these are: - Lipase, which digests lipids, - Carbohydrases, which digest carbohydrates (e.g., sugars), - Proteases, which digest proteins, - Nucleases, which digest nucleic acids. - Phosphatases, which digest phosphoric acid monoesters Lysosomal enzymes are synthesized in the cytosol and the endoplasmic reticulum, where they receive a mannose-6-phosphate tag that targets them for the lysosome. Aberrant lysosomal targeting causes inclusion-cell disease, whereby enzymes do not properly reach the lysosome, resulting in accumulation of waste within these organelles. # Functions The lysosomes are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (where old or unneeded organelles or proteins, or microbes which have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to autophagic cell death, a form of programmed self-destruction, or autolysis, of the cell, which means that the cell is digesting itself. Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound. Lysosomes also do much of the cellular digestion required to digest tails of tadpoles and to remove the web from the fingers of a 3-6 month old fetus. This process of programmed cell death is called apoptosis. # Clinical relevance There are a number of illnesses that are caused by the malfunction of the lysosomes or one of their digestive proteins, e.g., Tay-Sachs disease, or Pompe's disease. These are caused by a defective or missing digestive protein, which leads to the accumulation of substrates within the cell, impairing metabolism. Broadly, these can be classified as mucopolysaccharidoses, GM2 gangliosidoses, lipid storage disorders, glycoproteinoses, mucolipidoses, or leukodystrophies. # Structure Small round structures that contain chemicals. # Additional images - Proteins in different cellular compartments and structures tagged with green fluorescent protein.	Lysosome Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] # Overview Lysosomes are organelles that contain digestive enzymes (acid hydrolases). They digest excess or worn out organelles, food particles, and engulfed viruses or bacteria. The membrane surrounding a lysosome prevents the digestive enzymes inside from destroying the cell. Lysosomes fuse with vacuoles and dispense their enzymes into the vacuoles, digesting their contents. They are built in the Golgi apparatus. The name lysosome derives from the Greek words lysis, which means dissolution or destruction, and soma, which means body. They are frequently nicknamed "suicide-bags" or "suicide-sacs" by cell biologists due to their role in autolysis. Lysosomes were discovered by the Belgian cytologist Christian de Duve in 1949. # Acidic environment At pH 4.8, the interior of the lysosomes is more acidic than the cytosol (pH 7.2). The lysosome single membrane stabilizes the low pH by pumping in protons (H+) from the cytosol via proton pumps and chloride ion channels. The membrane also protects the cytosol, and therefore the rest of the cell, from the degradative enzymes within the lysosome. For this reason, should a lysosome's acid hydrolases leak into the cytosol, their potential to damage the cell will be reduced, because they will not be at their optimum pH! # Enzymes Some important enzymes in these are: - Lipase, which digests lipids, - Carbohydrases, which digest carbohydrates (e.g., sugars), - Proteases, which digest proteins, - Nucleases, which digest nucleic acids. - Phosphatases, which digest phosphoric acid monoesters Lysosomal enzymes are synthesized in the cytosol and the endoplasmic reticulum, where they receive a mannose-6-phosphate tag that targets them for the lysosome. Aberrant lysosomal targeting causes inclusion-cell disease, whereby enzymes do not properly reach the lysosome, resulting in accumulation of waste within these organelles. # Functions The lysosomes are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (where old or unneeded organelles or proteins, or microbes which have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to autophagic cell death, a form of programmed self-destruction, or autolysis, of the cell, which means that the cell is digesting itself. Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound. Lysosomes also do much of the cellular digestion required to digest tails of tadpoles and to remove the web from the fingers of a 3-6 month old fetus. This process of programmed cell death is called apoptosis.[1] # Clinical relevance There are a number of illnesses that are caused by the malfunction of the lysosomes or one of their digestive proteins, e.g., Tay-Sachs disease, or Pompe's disease. These are caused by a defective or missing digestive protein, which leads to the accumulation of substrates within the cell, impairing metabolism. Broadly, these can be classified as mucopolysaccharidoses, GM2 gangliosidoses, lipid storage disorders, glycoproteinoses, mucolipidoses, or leukodystrophies. # Structure Small round structures that contain chemicals. # Additional images - Proteins in different cellular compartments and structures tagged with green fluorescent protein.	https://www.wikidoc.org/index.php/Lysosomal
5120c533ab1a996bbbae6e88828200bd3df468ac	wikidoc	Lysozyme	Lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase is an antimicrobial enzyme produced by animals that forms part of the innate immune system. Lysozyme is a glycoside hydrolase that catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan, which is the major component of gram-positive bacterial cell wall. This hydrolysis in turn compromises the integrity of bacterial cell walls causing lysis of the bacteria. Lysozyme is abundant in secretions including tears, saliva, human milk, and mucus. It is also present in cytoplasmic granules of the macrophages and the polymorphonuclear neutrophils (PMNs). Large amounts of lysozyme can be found in egg white. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure, making them part of the same family. In humans, the lysozyme enzyme is encoded by the LYZ gene. Lysozyme is thermally stable, with a melting point reaching up to 72 ℃ at pH 5.0. However, in human milk it loses activity very quickly at that temperature. Its isoelectric point is 11.35. In a large range of pH (6-9) lysozyme can survive. # Function and mechanism The enzyme functions by attacking, hydrolyzing, and breaking glycosidic bonds in peptidoglycans. The enzyme can also break glycosidic bonds in chitin, although not as effectively as true chitinases. Lysozymes active site binds the peptidoglycan molecule in the prominent cleft between its two domains. It attacks peptidoglycans (found in the cell walls of bacteria, especially Gram-positive bacteria), its natural substrate, between N-acetylmuramic acid (NAM) and the fourth carbon atom of N-acetylglucosamine (NAG). Shorter saccharides like tetrasaccharide have also shown to be viable substrates but via an intermediate with a longer chain. Chitin has also been shown to be a viable lysozyme substrate. Artificial substrates have also been developed and used in lysozyme. ## Mechanism ### Phillips The Phillips Mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and electrostatic stabilization of an oxo-carbenium intermediate. From X-ray crystallographic data, Phillips proposed the active site of the enzyme, where a hexasaccharide binds. The lysozyme distorts the fourth sugar (in the D or -1 subsite) in the hexasaccharide into a half-chair conformation. In this stressed state, the glycosidic bond is more easily broken. An ionic intermediate containing an oxo-carbenium is created as a result of the glycosidic bond breaking. Thus distortion causing the substrate molecule to adopt a strained conformation similar to that of the transition state will lower the energy barrier of the reaction. The proposed oxo-carbonium intermediate was speculated to be electrostatically stabilized by aspartate and glutamate residues in the active site by Arieh Warshel in 1978. The electrostatic stabilization argument was based on comparison to bulk water, the reorientation of water dipoles can cancel out the stabilizing energy of charge interaction. In Warshel's model, the enzyme acts as a super-sovlent, which fixes the orientation of ion pairs and provides super-solvation (very good stabilization of ion pairs), and especially lower the energy when to ions are close to each other. The rate-determining step(RDS) in this mechanism is related to formation of the oxo-carbenium intermediate. There were some contradictory results to indicate the exact RDS. By tracing the formation of product (p-nitrophenol), it was discovered that the RDS can change over different temperatures, which was a reason for those contradictory results. At a higher temperature the RDS is formation of glycosyl enzyme intermediate and at a lower temperature the break down of that intermediate. ### Koshland In an early debate in 1969, Dahlquist proposed a covalent mechanism for lysozyme based on kinetic isotope effect, but for a long time the ionic mechanism was more accepted. In 2001, a revised mechanism was proposed by Vocadlo via a covalent but not ionic intermediate. Evidence from ESI-MS analysis indicated a covalent intermediate. A 2-fluoro substituted substrate was used to lower the reaction rate and accumulate an intermediate for characterization. The amino acid side-chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whereas Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The Glu35 reacts with water to form hydroxyl ion, a stronger nucleophile than water, which then attacks the glycosyl enzyme intermediate, to give the product of hydrolysis and leaving the enzyme unchanged. This covalent mechanism was named after Koshland, who first proposed this type of mechanism. More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have been using the crystal of HEWL and predict the existence of a covalent intermediate. Evidence for the ESI-MS and X-ray structures indicate the existence of covalent intermediate, but primarily rely on using a less active mutant or non-native substrate. Thus, QM/MM molecular dynamics provides the unique ability to directly investigate the mechanism of wild-type HEWL and native substrate. The calculations revealed that the covalent intermediate from the Koshland mechanism is ~30 kcal/mol more stable than the ionic intermediate from the Phillips mechanism. These calculation demonstrate that the ionic intermediate is extremely energetically unfavorable and the covalent intermediates observed from experiments using less active mutant or non-native substrates provide useful insight into the mechanism of wild-type HEWL. ## Inhibition Imidazole derivatives can form a charge-transfer complex with some residues (in or outside active center) to achieve a competitive inhibition of lysozyme. In Gram-negative bacteria, the lipopolysaccharide acts as a non-competitive inhibitior by highly-favored binding with lysozyme. ## Non-enzymatic action Despite that the muramidase activity of lysozyme has been supposed to play the key role for its antibacterial properties, evidence of its non-enzymatic action was also reported. For example, blocking the catalytic activity of lysozyme by mutation of critical amino acid in the active site (52-Asp -> 52-Ser) does not eliminate its antimicrobial activity. The lectin-like ability of lysozyme to recognize bacterial carbohydrate antigen without lytic activity was reported for tetrasaccharide related to lipopolysaccharide of Klebsiella pneumoniae. Also, lysozyme interacts with antibodies and T-cell receptors. ## Enzyme conformation changes Lysozyme exhibits two conformations: an open active state and a closed inactive state. The catalytic relevance was examined with single walled carbon nanotubes (SWCN) field effect transitors (FETs), where a singular lysozyme was bound to the SWCN FET. Electronically monitoring the lysozyme showed two conformations, an open active site and a closed inactive site. In its active state lysozyme is able to processively hydrolyze its substrate, breaking on average 100 bonds at a rate of 15 per second. In order to bind a new substrate and move from the closed inactive state to the open active state requires two conformation step changes, while inactivation requires one step. # Role in disease and therapy Lysozyme is part of the innate immune system. Reduced lysozyme levels have been associated with bronchopulmonary dysplasia in newborns. Piglets fed with human lysozyme milk can recover from diarrheal disease caused by E. coli faster. The concentration of lysozyme in human milk is 1,600 to 3,000 times greater than the concentration in livestock milk. Human lysozyme is more active than hen egg white lysozyme. A transgenic line of goats (with a founder named "Artemis") were developed to produce milk with human lysozyme to protect children from diarrhea if they can't get the benefits of human breastfeeding. Since lysozyme is a natural form of protection from Gram-positive pathogens like Bacillus and Streptococcus, it plays an important role in immunology of infants in human milk feeding. Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is, instead, protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results. In certain cancers (especially myelomonocytic leukemia) excessive production of lysozyme by cancer cells can lead to toxic levels of lysozyme in the blood. High lysozyme blood levels can lead to kidney failure and low blood potassium, conditions that may improve or resolve with treatment of the primary malignancy. Serum lysozyme is much less specific for diagnosis of sarcoidosis than serum angiotensin converting enzyme; however, since it is more sensitive, it is used as a marker of sarcoidosis disease activity and is suitable for disease monitoring in proven cases. # Chemical synthesis The first chemical synthesis of a lysozyme protein was attempted by Prof. George W. Kenner and his group at the University of Liverpool in England. This was finally achieved in 2007 by Steve Kent at the University of Chicago who made a synthetic functional lysozyme molecule. # Other applications Lysozyme crystals have been used to grow other functional materials for catalysis and biomedical applications. Lysozyme is a commonly used enzyme for lysing gram positive bacteria. Due to the unique function of lysozyme in which it can digest the cell wall and causes osmotic shock (burst the cell by suddenly changing solute concentration around the cell and thus the osmotic pressure), lysozyme is commonly used in lab setting to release proteins from bacterium periplasm while the inner membrane remains sealed as vesicles called the spheroplast. For example, E.Coli can be lysed using Lysozyme in order to free the contents of the Periplasm space. It is especially useful in lab setting for trying to collect the contents of the periplasm. Lysozyme treatment is optimal at particular temperatures, pH ranges, and salt concentrations. Lysozyme activity increases with increasing temperatures, up to 60 degrees Celsius, with a pH range of 6.0-7.0. The salts present also affect lysozyme treatment, where some assert inhibitory effects, and others promote lysis via lysozyme treatment. Sodium chloride induces lysis, but at high concentrations, it is an active inhibitor of lysis. Similar observations have been seen with the use of potassium salts. Slight variations are present due to differences in bacterial strains. # History The antibacterial property of hen egg white, due to the lysozyme it contains, was first observed by Laschtschenko in 1909, although it was not until 1922 that the name 'lysozyme' was coined, by Alexander Fleming, the second scientist to discover penicillin. But according to one publication, it was Fleming "who first clearly showed that an enzymic substance present in a wide variety of secretions is capable of rapidly lysing (ie.., dissolving) certain bacteria, particularly a yellow "coccus" that he studied". Fleming first observed the antibacterial action of lysozyme when he treated bacterial cultures with nasal mucus from a patient suffering from a head cold. Lysozyme was first crystallised by Edward Abraham in 1937 enabling the three-dimensional structure of hen egg white lysozyme to be described by David Chilton Phillips in 1965, when he obtained the first 2-ångström (200 pm) resolution model via X-ray crystallography. The structure was publicly presented at a Royal Institution lecture in 1965. Lysozyme was the second protein structure and the first enzyme structure to be solved via X-ray diffraction methods, and the first enzyme to be fully sequenced that contains all twenty common amino acids. As a result of Phillips' elucidation of the structure of lysozyme, it was also the first enzyme to have a detailed, specific mechanism suggested for its method of catalytic action. This work led Phillips to provide an explanation for how enzymes speed up a chemical reaction in terms of its physical structures. The original mechanism proposed by Phillips was more recently revised.	Lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase is an antimicrobial enzyme produced by animals that forms part of the innate immune system. Lysozyme is a glycoside hydrolase that catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan, which is the major component of gram-positive bacterial cell wall.[1] This hydrolysis in turn compromises the integrity of bacterial cell walls causing lysis of the bacteria. Lysozyme is abundant in secretions including tears, saliva, human milk, and mucus. It is also present in cytoplasmic granules of the macrophages and the polymorphonuclear neutrophils (PMNs). Large amounts of lysozyme can be found in egg white. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure, making them part of the same family.[2] In humans, the lysozyme enzyme is encoded by the LYZ gene.[3][4] Lysozyme is thermally stable, with a melting point reaching up to 72 ℃ at pH 5.0.[5] However, in human milk it loses activity very quickly at that temperature.[6] Its isoelectric point is 11.35. In a large range of pH (6-9) lysozyme can survive.[7] # Function and mechanism The enzyme functions by attacking, hydrolyzing, and breaking glycosidic bonds in peptidoglycans. The enzyme can also break glycosidic bonds in chitin, although not as effectively as true chitinases.[8] Lysozymes active site binds the peptidoglycan molecule in the prominent cleft between its two domains. It attacks peptidoglycans (found in the cell walls of bacteria, especially Gram-positive bacteria), its natural substrate, between N-acetylmuramic acid (NAM) and the fourth carbon atom of N-acetylglucosamine (NAG). Shorter saccharides like tetrasaccharide have also shown to be viable substrates but via an intermediate with a longer chain.[9] Chitin has also been shown to be a viable lysozyme substrate. Artificial substrates have also been developed and used in lysozyme.[10] ## Mechanism ### Phillips The Phillips Mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and electrostatic stabilization of an oxo-carbenium intermediate. From X-ray crystallographic data, Phillips proposed the active site of the enzyme, where a hexasaccharide binds. The lysozyme distorts the fourth sugar (in the D or -1 subsite) in the hexasaccharide into a half-chair conformation. In this stressed state, the glycosidic bond is more easily broken.[11] An ionic intermediate containing an oxo-carbenium is created as a result of the glycosidic bond breaking.[12] Thus distortion causing the substrate molecule to adopt a strained conformation similar to that of the transition state will lower the energy barrier of the reaction.[13] The proposed oxo-carbonium intermediate was speculated to be electrostatically stabilized by aspartate and glutamate residues in the active site by Arieh Warshel in 1978. The electrostatic stabilization argument was based on comparison to bulk water, the reorientation of water dipoles can cancel out the stabilizing energy of charge interaction. In Warshel's model, the enzyme acts as a super-sovlent, which fixes the orientation of ion pairs and provides super-solvation (very good stabilization of ion pairs), and especially lower the energy when to ions are close to each other.[14] The rate-determining step(RDS) in this mechanism is related to formation of the oxo-carbenium intermediate. There were some contradictory results to indicate the exact RDS. By tracing the formation of product (p-nitrophenol), it was discovered that the RDS can change over different temperatures, which was a reason for those contradictory results. At a higher temperature the RDS is formation of glycosyl enzyme intermediate and at a lower temperature the break down of that intermediate.[15] ### Koshland In an early debate in 1969, Dahlquist proposed a covalent mechanism for lysozyme based on kinetic isotope effect,[16] but for a long time the ionic mechanism was more accepted. In 2001, a revised mechanism was proposed by Vocadlo via a covalent but not ionic intermediate. Evidence from ESI-MS analysis indicated a covalent intermediate. A 2-fluoro substituted substrate was used to lower the reaction rate and accumulate an intermediate for characterization.[17] The amino acid side-chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whereas Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The Glu35 reacts with water to form hydroxyl ion, a stronger nucleophile than water, which then attacks the glycosyl enzyme intermediate, to give the product of hydrolysis and leaving the enzyme unchanged.[18] This covalent mechanism was named after Koshland, who first proposed this type of mechanism.[19] More recently, quantum mechanics/ molecular mechanics (QM/MM) molecular dynamics simulations have been using the crystal of HEWL and predict the existence of a covalent intermediate.[20] Evidence for the ESI-MS and X-ray structures indicate the existence of covalent intermediate, but primarily rely on using a less active mutant or non-native substrate. Thus, QM/MM molecular dynamics provides the unique ability to directly investigate the mechanism of wild-type HEWL and native substrate. The calculations revealed that the covalent intermediate from the Koshland mechanism is ~30 kcal/mol more stable than the ionic intermediate from the Phillips mechanism.[20] These calculation demonstrate that the ionic intermediate is extremely energetically unfavorable and the covalent intermediates observed from experiments using less active mutant or non-native substrates provide useful insight into the mechanism of wild-type HEWL. ## Inhibition Imidazole derivatives can form a charge-transfer complex with some residues (in or outside active center) to achieve a competitive inhibition of lysozyme.[21] In Gram-negative bacteria, the lipopolysaccharide acts as a non-competitive inhibitior by highly-favored binding with lysozyme.[22] ## Non-enzymatic action Despite that the muramidase activity of lysozyme has been supposed to play the key role for its antibacterial properties, evidence of its non-enzymatic action was also reported. For example, blocking the catalytic activity of lysozyme by mutation of critical amino acid in the active site (52-Asp -> 52-Ser) does not eliminate its antimicrobial activity.[23] The lectin-like ability of lysozyme to recognize bacterial carbohydrate antigen without lytic activity was reported for tetrasaccharide related to lipopolysaccharide of Klebsiella pneumoniae.[24] Also, lysozyme interacts with antibodies and T-cell receptors.[25] ## Enzyme conformation changes Lysozyme exhibits two conformations: an open active state and a closed inactive state. The catalytic relevance was examined with single walled carbon nanotubes (SWCN) field effect transitors (FETs), where a singular lysozyme was bound to the SWCN FET.[26] Electronically monitoring the lysozyme showed two conformations, an open active site and a closed inactive site. In its active state lysozyme is able to processively hydrolyze its substrate, breaking on average 100 bonds at a rate of 15 per second. In order to bind a new substrate and move from the closed inactive state to the open active state requires two conformation step changes, while inactivation requires one step. # Role in disease and therapy Lysozyme is part of the innate immune system. Reduced lysozyme levels have been associated with bronchopulmonary dysplasia in newborns.[27] Piglets fed with human lysozyme milk can recover from diarrheal disease caused by E. coli faster. The concentration of lysozyme in human milk is 1,600 to 3,000 times greater than the concentration in livestock milk. Human lysozyme is more active than hen egg white lysozyme. A transgenic line of goats (with a founder named "Artemis") were developed to produce milk with human lysozyme to protect children from diarrhea if they can't get the benefits of human breastfeeding.[28][29] Since lysozyme is a natural form of protection from Gram-positive pathogens like Bacillus and Streptococcus,[30] it plays an important role in immunology of infants in human milk feeding.[31] Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is, instead, protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results. In certain cancers (especially myelomonocytic leukemia) excessive production of lysozyme by cancer cells can lead to toxic levels of lysozyme in the blood. High lysozyme blood levels can lead to kidney failure and low blood potassium, conditions that may improve or resolve with treatment of the primary malignancy. Serum lysozyme is much less specific for diagnosis of sarcoidosis than serum angiotensin converting enzyme; however, since it is more sensitive, it is used as a marker of sarcoidosis disease activity and is suitable for disease monitoring in proven cases.[32] # Chemical synthesis The first chemical synthesis of a lysozyme protein was attempted by Prof. George W. Kenner and his group at the University of Liverpool in England.[33] This was finally achieved in 2007 by Steve Kent at the University of Chicago who made a synthetic functional lysozyme molecule.[34] # Other applications Lysozyme crystals have been used to grow other functional materials for catalysis and biomedical applications.[35][36][37] Lysozyme is a commonly used enzyme for lysing gram positive bacteria.[38] Due to the unique function of lysozyme in which it can digest the cell wall and causes osmotic shock (burst the cell by suddenly changing solute concentration around the cell and thus the osmotic pressure), lysozyme is commonly used in lab setting to release proteins from bacterium periplasm while the inner membrane remains sealed as vesicles called the spheroplast.[39][40] For example, E.Coli can be lysed using Lysozyme in order to free the contents of the Periplasm space. It is especially useful in lab setting for trying to collect the contents of the periplasm.[1] Lysozyme treatment is optimal at particular temperatures, pH ranges, and salt concentrations. Lysozyme activity increases with increasing temperatures, up to 60 degrees Celsius, with a pH range of 6.0-7.0. The salts present also affect lysozyme treatment, where some assert inhibitory effects, and others promote lysis via lysozyme treatment. Sodium chloride induces lysis, but at high concentrations, it is an active inhibitor of lysis. Similar observations have been seen with the use of potassium salts. Slight variations are present due to differences in bacterial strains.[41] # History The antibacterial property of hen egg white, due to the lysozyme it contains, was first observed by Laschtschenko in 1909,[42] although it was not until 1922 that the name 'lysozyme' was coined, by Alexander Fleming, the second scientist to discover penicillin.[43] [44] But according to one publication, it was Fleming "who first clearly showed that an enzymic substance present in a wide variety of secretions is capable of rapidly lysing (ie.., dissolving) certain bacteria, particularly a yellow "coccus" that he studied". [45] Fleming first observed the antibacterial action of lysozyme when he treated bacterial cultures with nasal mucus from a patient suffering from a head cold.[44] Lysozyme was first crystallised by Edward Abraham in 1937 enabling the three-dimensional structure of hen egg white lysozyme to be described by David Chilton Phillips in 1965, when he obtained the first 2-ångström (200 pm) resolution model via X-ray crystallography.[46][47] The structure was publicly presented at a Royal Institution lecture in 1965.[48] Lysozyme was the second protein structure and the first enzyme structure to be solved via X-ray diffraction methods, and the first enzyme to be fully sequenced that contains all twenty common amino acids.[49] As a result of Phillips' elucidation of the structure of lysozyme, it was also the first enzyme to have a detailed, specific mechanism suggested for its method of catalytic action.[50][51][52] This work led Phillips to provide an explanation for how enzymes speed up a chemical reaction in terms of its physical structures. The original mechanism proposed by Phillips was more recently revised.[17]	https://www.wikidoc.org/index.php/Lysozyme
a06d2b89e67a9c185194ea2b997ddd7ae78f4df0	wikidoc	MAP1LC3A	MAP1LC3A Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene. Two transcript variants encoding different isoforms have been found for this gene. # Function MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B. MAPLC3A is one of the mammalian homologues of yeast ATG8, an important marker and effector of autophagy. # Regulation MAP1LC3A is regulated by several post-translational modifications. These include covalent linkage of the C-terminus to phosphatidylethanolamine in autophagic membranes, and phosphorylation by protein kinase A, which downregulates its autophagy functions. Noncovalent interactions are important for its cargo targeting functions in selective autophagy. For example, it has been shown to interact with sequestosome 1.	MAP1LC3A Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene.[1][2][3] Two transcript variants encoding different isoforms have been found for this gene. # Function MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B.[3] MAPLC3A is one of the mammalian homologues of yeast ATG8, an important marker and effector of autophagy.[4] # Regulation MAP1LC3A is regulated by several post-translational modifications. These include covalent linkage of the C-terminus to phosphatidylethanolamine in autophagic membranes, and phosphorylation by protein kinase A,[5] which downregulates its autophagy functions. Noncovalent interactions are important for its cargo targeting functions in selective autophagy. For example, it has been shown to interact with sequestosome 1.[6]	https://www.wikidoc.org/index.php/MAP1LC3A
59dfaacd2d36168e9ed7bae586bc5e9530fed358	wikidoc	MAP1LC3B	MAP1LC3B Microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes. # Discovery LC3 was originally identified as a microtubule associated protein in rat brain. However it was later found that the primary function of LC3 is in autophagy, a process that involves the bulk degradation of cytoplasmic components. ## The ATG8 protein family MAP1LC3B is a member of the highly conserved ATG8 protein family. ATG8 proteins are present in all known eukaryotic organisms. The animal ATG8 family comprises three subfamilies: (i) microtubule-associated protein 1 light chain 3 (MAP1LC3); (ii) Golgi-associated ATPase enhancer of 16 kDa (GATE-16); and (iii) γ-amino-butyric acid receptor-associate protein (GABARAP). MAP1LC3B is one of the four genes in the MAP1LC3 subfamily (others include MAP1LC3A, MAP1LC3C, and MAP1LC3B2). # Function ## Cytoplasmic LC3 Newly synthesized LC3's C-terminus is hydroylzed by a cysteine protease called ATG4B exposing Gly120, termed LC3-I. LC3-I, through a series of ubiquitin-like reactions involving enzymes ATG7, ATG3, and ATG12-ATG5-ATG16, becomes conjugated to the head group of the lipid phosphatidylethanolamine. The lipid modified form of LC3, referred to as LC3-II, is believed to be involved in autophagosome membrane expansion and fusion events. However, the exact role of LC3 in the autophagic pathway is still discussed, and the question of whether LC3 is required for autophagy is debated since knockdown of MAP1LC3B is compensated by the other members of the MAP1LC3 subfamily. Previous studies showed that MAP1LC3B knock out mice develop normally, possibly due to a then unknown compensatory mechanism. Further work, however, demonstrated that LC3 is required for autophagy by simultaneously down-regulating all of the MAP1LC3 subfamily members. While yet another study argues that MAP1LC3 knockdown does to not affect bulk autophagy, whereas its GABARAP family members are crucial for the process. LC3 also functions—together with autophagy receptors (e.g. SQSTM1)--in the selective capture of cargo for autophagic degradation. Independent of autophagosomes, a single soluble LC3 is associated with an approximately 500 kDa complex in the cytoplasm. ## Nuclear LC3 The importance of the nuclear functions of autophagy proteins should not be underestimated. A large pool of LC3 is present in the nucleus of a variety of different cell types. In response to starvation, nuclear LC3 is deacetylated and trafficked out of the nucleus into the cytoplasm where it functions in autophagy. Nuclear LC3 interacts with lamin B1, and participates in the degradation of nuclear lamina. LC3 is also enriched in nucleoli via its triple arginine motif, and associates with a number of different nuclear and nucleolar constituents including: MAP1B, tubulin, and several ribosomal proteins. # Structure LC3 shares structural homology with ubiquitin, and thus has been termed a ubiquitin-like protein. LC3 has a LDS (LIR docking site)/hydrophobic binding interface in the N terminus which interacts with LIR (LC3 Interacting Region) containing proteins. This domain is rich in hydrophobic amino acids, the mutation of which impairs the ability of LC3 binding with LIR containing proteins, many of which are autophagy cargo adapter proteins. For example, sequestosome (SQSTM1) interacts with Phe 52 and Leu53 aminoacids present in hydrophobic binding interface of LC3 and any mutation of these amino acids prevents LC3 interaction with SQSTM1. # Post-translational regulation	MAP1LC3B Microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) is a protein that in humans is encoded by the MAP1LC3B gene.[1] LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.[2] # Discovery LC3 was originally identified as a microtubule associated protein in rat brain.[3] However it was later found that the primary function of LC3 is in autophagy, a process that involves the bulk degradation of cytoplasmic components. ## The ATG8 protein family MAP1LC3B is a member of the highly conserved ATG8 protein family. ATG8 proteins are present in all known eukaryotic organisms. The animal ATG8 family comprises three subfamilies: (i) microtubule-associated protein 1 light chain 3 (MAP1LC3); (ii) Golgi-associated ATPase enhancer of 16 kDa (GATE-16); and (iii) γ-amino-butyric acid receptor-associate protein (GABARAP). MAP1LC3B is one of the four genes in the MAP1LC3 subfamily (others include MAP1LC3A, MAP1LC3C, and MAP1LC3B2).[4] # Function ## Cytoplasmic LC3 Newly synthesized LC3's C-terminus is hydroylzed by a cysteine protease called ATG4B exposing Gly120, termed LC3-I.[5] LC3-I, through a series of ubiquitin-like reactions involving enzymes ATG7, ATG3, and ATG12-ATG5-ATG16, becomes conjugated to the head group of the lipid phosphatidylethanolamine.[6] The lipid modified form of LC3, referred to as LC3-II, is believed to be involved in autophagosome membrane expansion and fusion events.[7] However, the exact role of LC3 in the autophagic pathway is still discussed, and the question of whether LC3 is required for autophagy is debated since knockdown of MAP1LC3B is compensated by the other members of the MAP1LC3 subfamily. Previous studies showed that MAP1LC3B knock out mice develop normally, possibly due to a then unknown compensatory mechanism.[8] Further work, however, demonstrated that LC3 is required for autophagy by simultaneously down-regulating all of the MAP1LC3 subfamily members.[9] While yet another study argues that MAP1LC3 knockdown does to not affect bulk autophagy, whereas its GABARAP family members are crucial for the process.[10][10] LC3 also functions—together with autophagy receptors (e.g. SQSTM1)--in the selective capture of cargo for autophagic degradation.[11] Independent of autophagosomes, a single soluble LC3 is associated with an approximately 500 kDa complex in the cytoplasm.[12] ## Nuclear LC3 The importance of the nuclear functions of autophagy proteins should not be underestimated. A large pool of LC3 is present in the nucleus of a variety of different cell types.[13] In response to starvation, nuclear LC3 is deacetylated and trafficked out of the nucleus into the cytoplasm where it functions in autophagy.[14] Nuclear LC3 interacts with lamin B1, and participates in the degradation of nuclear lamina.[15] LC3 is also enriched in nucleoli via its triple arginine motif, and associates with a number of different nuclear and nucleolar constituents including: MAP1B, tubulin, and several ribosomal proteins.[16] # Structure LC3 shares structural homology with ubiquitin, and thus has been termed a ubiquitin-like protein.[17] LC3 has a LDS (LIR docking site)/hydrophobic binding interface in the N terminus which interacts with LIR (LC3 Interacting Region) containing proteins.[12] This domain is rich in hydrophobic amino acids, the mutation of which impairs the ability of LC3 binding with LIR containing proteins, many of which are autophagy cargo adapter proteins. For example, sequestosome (SQSTM1) interacts with Phe 52 and Leu53 aminoacids present in hydrophobic binding interface of LC3 and any mutation of these amino acids prevents LC3 interaction with SQSTM1. # Post-translational regulation	https://www.wikidoc.org/index.php/MAP1LC3B
4b4f47ff48c85c3901d56b6eb2008b1b249e2615	wikidoc	MAPK8IP1	MAPK8IP1 C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 gene. The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes. # Interactions MAPK8IP1 has been shown to interact with MAP3K10, DUSP16, Mitogen-activated protein kinase 9, MAPK8, LRP2, LRP1, MAP3K12, MAP2K7, MAPK8IP2 and MAP3K11.	MAPK8IP1 C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 gene.[1][2] The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes.[3] # Interactions MAPK8IP1 has been shown to interact with MAP3K10,[4] DUSP16,[5] Mitogen-activated protein kinase 9,[4][6] MAPK8,[6][7] LRP2,[8][9] LRP1,[8] MAP3K12,[4] MAP2K7,[4] MAPK8IP2[4] and MAP3K11.[4]	https://www.wikidoc.org/index.php/MAPK8IP1
405923305a9cde4264e1c2f6bcc8dee777b45419	wikidoc	MAPK8IP2	MAPK8IP2 C-jun-amino-terminal kinase-interacting protein 2 is a protein or the name of the gene that encodes it. The gene is also known as Islet-Brain-2 (IB2). This protein is highly expressed in the brain and is almost always deleted in Phelan-McDermid syndrome (PMS). MAPK8IP2 appears to regulate the ratio of AMPA receptors to NMDA receptors at glutamate synapses, and thus may be an important contributor to the intellectual dysfunction and related neurological manifestations characteristic of PMS. The protein encoded by this gene is closely related to MAPK8IP1/IB1/JIP-1, a scaffold protein that is involved in the c-Jun amino-terminal kinase signaling pathway. This protein is expressed in brain and pancreatic cells. It has been shown to interact with, and regulate the activity of MAPK8/JNK1, and MAP2K7/MKK7 kinases. This protein thus is thought to function as a regulator of signal transduction by protein kinase cascade in brain and pancreatic beta-cells. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene. # Interactions MAPK8IP2 has been shown to interact with MAP3K10, Mitogen-activated protein kinase 9, LRP2, LRP1, MAPK8IP3, MAP3K12, MAPK8IP1, MAP2K7 and MAP3K11.	MAPK8IP2 C-jun-amino-terminal kinase-interacting protein 2 is a protein or the name of the gene that encodes it.[1][2] The gene is also known as Islet-Brain-2 (IB2). This protein is highly expressed in the brain and is almost always deleted in Phelan-McDermid syndrome (PMS). MAPK8IP2 appears to regulate the ratio of AMPA receptors to NMDA receptors at glutamate synapses,[3] and thus may be an important contributor to the intellectual dysfunction and related neurological manifestations characteristic of PMS. The protein encoded by this gene is closely related to MAPK8IP1/IB1/JIP-1, a scaffold protein that is involved in the c-Jun amino-terminal kinase signaling pathway. This protein is expressed in brain and pancreatic cells. It has been shown to interact with, and regulate the activity of MAPK8/JNK1, and MAP2K7/MKK7 kinases. This protein thus is thought to function as a regulator of signal transduction by protein kinase cascade in brain and pancreatic beta-cells. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene.[2] # Interactions MAPK8IP2 has been shown to interact with MAP3K10,[1] Mitogen-activated protein kinase 9,[1] LRP2,[4][5] LRP1,[4] MAPK8IP3,[6] MAP3K12,[1] MAPK8IP1,[1] MAP2K7[1][7] and MAP3K11.[1]	https://www.wikidoc.org/index.php/MAPK8IP2
0c1084905c59c6ccd932f44a9553c29d2d469458	wikidoc	MAPK8IP3	MAPK8IP3 C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. # Interactions MAPK8IP3 has been shown to interact with ASK1, C-Raf, PTK2, MAPK10, Mitogen-activated protein kinase 9, MAPK8, MAP2K1, KLC2, MAP2K7, KLC1, MAPK8IP2 and MAP2K4.	MAPK8IP3 C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene.[1][2][3] The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[3] # Interactions MAPK8IP3 has been shown to interact with ASK1,[4] C-Raf,[1][5] PTK2,[6] MAPK10,[1][2][4] Mitogen-activated protein kinase 9,[1][2] MAPK8,[1][2] MAP2K1,[1][5] KLC2,[7] MAP2K7,[2][4] KLC1,[7] MAPK8IP2[2] and MAP2K4.[1][4]	https://www.wikidoc.org/index.php/MAPK8IP3
edef61fd204d50f52e6f050116478ce877c76ace	wikidoc	MAPKAPK5	MAPKAPK5 MAP kinase-activated protein kinase 5 is an enzyme that in humans is encoded by the MAPKAPK5 gene. The protein encoded by this gene is a member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases, including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. In vitro, this kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately-spliced transcript variants of this gene encoding distinct isoforms have been reported. A link between Alzheimer's disease and reduced levels of MAPKAPK5 has been proposed. Clinical trials may confirm if this is the case.	MAPKAPK5 MAP kinase-activated protein kinase 5 is an enzyme that in humans is encoded by the MAPKAPK5 gene.[1][2] The protein encoded by this gene is a member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases, including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. In vitro, this kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately-spliced transcript variants of this gene encoding distinct isoforms have been reported.[2] A link between Alzheimer's disease and reduced levels of MAPKAPK5 has been proposed. Clinical trials may confirm if this is the case.	https://www.wikidoc.org/index.php/MAPKAPK5
f772242f38c6ffcacea9385aa927434cfef60e51	wikidoc	MGC50722	MGC50722 MGC50722, also known as uncharacterized protein LOC399693, is a protein that in humans is encoded by the MGC50722 gene (Mammalian Gene Collection Project Gene 50722). This 965 amino acid human protein has a molecular weight of 104.495 kDa and one domain of unknown function (DUF390). Generally conserved across mammals, this quickly evolving gene shows relatively low expression in most human tissues except in the testis. # Gene The entire human gene is 40,364 base pairs in length, while the unprocessed mRNA is 25,960 base pairs long. After splicing of introns the 10 exon gene has a final mRNA length of 3,596 base pairs that encodes for 965 amino acids. ## Locus Human MGC50722 is located on the minus strand of chromosome 9 in the region q34 of the human genome (NCBI Gene ID: 399693). The most characterized gene in this region of the human genome is GPSM1, which encodes the G-protein-signaling modulator 1 protein. # Homology and evolution ## Paralogs It was found that the centrosome-associated protein 350 (CEP350) was the only possible paralog to protein MGC50722 in humans. CEP350 is a 3117 amino acid long protein and aligns with protein MGC50722 at its N-terminus. This indicates the paralog spacing is very distant for when MGC50722 split from CEP350. ## Orthologs Compete orthologs for protein MGC50722 are found only in mammals, where most conservation is found within the N-terminus and DUF390. ## Distant homologs The most distant homolog detectable is in cartilaginous fish (462.5 MYA). ## Homologous domains The domain of unknown function 390 (pfam04094: DUF390) is part of a family of proteins that have only been identified within the rice genome. Although this domain’s function is unknown, it may be some kind of transposable element. # Protein ## Primary sequence and isoforms Human protein MGC50722 is 104.495 kDa, with an isoelectric point of 10.24. A mixed charged cluster of amino acids is present between positions 146 and 182, which seems to be conserved in primates, but not present in other mammals. There are also 6 predicted isoforms found in human. ## Subcellualar localization signals PSORTII servers predict 5 nuclear localization signals in the human protein MGC50722. When ortholog sequences to the human protein were run through PSORT II, the predicted nuclear subcellular localization was a consensus prediction. ## Post-translational modifications Human protein MGC50722 ortholog in mice, 4932418E24Rik protein, has experimentally determined phosphorylation sites at S588, S591, and S670 in the testis (pTestis ID: PT-MM-02686). Prediction servers at ExPASy also predict more phosphorylation sites (NetPhos 2.0 Server), a N-termnial acetylation site (NetAcet 1.0 Server), glycation sites (NetGlycate 1.0 Server), and a GalNAc O-glycosylation site (NetOGlyc 4.0 Server) at conserved residues in the human MGC50722 protein. ## Secondary structure Prediction models characterized protein MGC50722 as mostly disordered, but two regions of coiled-coils. ## Protein internal structure and features # Potential function The function of protein MGC50722 is unknown. Given that it is preferentially expressed in the testis and appears to be subcellularly localized in the nucleus, it could play an important role in gamete cells. # Interacting proteins Due the recent identification of this gene and its protein, interaction databases (MINT, STRING, IntAct, and BioGRID) have not identified any interactions. More data would expand the characterization of MGC50722. # Expression Expression levels of human MGC50722 appear to low/absent in most cell types, with the highest and most abundant expression shown to be in the testis (GEO Profile IDs: 48997768 and 49895282). A lung cancer study also showed that MGC50722 was expressed in CD4+ T-Cells of normal human tissue samples. ## Promoter The transcriptional start site for MGC50722 aligns best with SPZ1, SORY, SP1F, and FAST transcription factor binding sites. # Clinical significance A significant GEO Profile relating to MGC50722 was a study done on male fertility in humans looking at the disease teratozoospermia (GEO Profile ID: 38113951). Teratozoospermia is a condition where during the development of mature sperm cells morphology is altered, thus leading to, in some cases, male infertility. Gene expression shows that in normal human subjects MGC50722 is expressed, while in subjects with teratozoospermia expression levels drop significantly or shut off.	MGC50722 MGC50722, also known as uncharacterized protein LOC399693, is a protein that in humans is encoded by the MGC50722 gene (Mammalian Gene Collection Project Gene 50722[1]). This 965 amino acid human protein has a molecular weight of 104.495 kDa and one domain of unknown function (DUF390).[2] Generally conserved across mammals, this quickly evolving gene shows relatively low expression in most human tissues except in the testis.[3][4] # Gene The entire human gene is 40,364 base pairs in length, while the unprocessed mRNA is 25,960 base pairs long. After splicing of introns the 10 exon gene has a final mRNA length of 3,596 base pairs that encodes for 965 amino acids.[2][5][6] ## Locus Human MGC50722 is located on the minus strand of chromosome 9 in the region q34 of the human genome (NCBI Gene ID: 399693). The most characterized gene in this region of the human genome is GPSM1, which encodes the G-protein-signaling modulator 1 protein.[7] # Homology and evolution ## Paralogs It was found that the centrosome-associated protein 350 (CEP350) was the only possible paralog to protein MGC50722 in humans. CEP350 is a 3117 amino acid long protein and aligns with protein MGC50722 at its N-terminus. This indicates the paralog spacing is very distant for when MGC50722 split from CEP350. ## Orthologs Compete orthologs for protein MGC50722 are found only in mammals, where most conservation is found within the N-terminus and DUF390. ## Distant homologs The most distant homolog detectable is in cartilaginous fish (462.5 MYA). ## Homologous domains The domain of unknown function 390 (pfam04094: DUF390) is part of a family of proteins that have only been identified within the rice genome. Although this domain’s function is unknown, it may be some kind of transposable element.[8] # Protein ## Primary sequence and isoforms Human protein MGC50722 is 104.495 kDa, with an isoelectric point of 10.24. A mixed charged cluster of amino acids is present between positions 146 and 182, which seems to be conserved in primates, but not present in other mammals. There are also 6 predicted isoforms found in human.[2] ## Subcellualar localization signals PSORTII servers predict 5 nuclear localization signals in the human protein MGC50722. When ortholog sequences to the human protein were run through PSORT II, the predicted nuclear subcellular localization was a consensus prediction. ## Post-translational modifications Human protein MGC50722 ortholog in mice, 4932418E24Rik protein, has experimentally determined phosphorylation sites at S588, S591, and S670 in the testis (pTestis ID: PT-MM-02686).[9][10][11] Prediction servers at ExPASy also predict more phosphorylation sites (NetPhos 2.0 Server), a N-termnial acetylation site (NetAcet 1.0 Server), glycation sites (NetGlycate 1.0 Server), and a GalNAc O-glycosylation site (NetOGlyc 4.0 Server) at conserved residues in the human MGC50722 protein. ## Secondary structure Prediction models characterized protein MGC50722 as mostly disordered, but two regions of coiled-coils. ## Protein internal structure and features # Potential function The function of protein MGC50722 is unknown. Given that it is preferentially expressed in the testis and appears to be subcellularly localized in the nucleus, it could play an important role in gamete cells. # Interacting proteins Due the recent identification of this gene and its protein, interaction databases (MINT, STRING, IntAct, and BioGRID) have not identified any interactions. More data would expand the characterization of MGC50722. # Expression Expression levels of human MGC50722 appear to low/absent in most cell types, with the highest and most abundant expression shown to be in the testis (GEO Profile IDs: 48997768 and 49895282).[13] A lung cancer study also showed that MGC50722 was expressed in CD4+ T-Cells of normal human tissue samples.[14] ## Promoter The transcriptional start site for MGC50722 aligns best with SPZ1, SORY, SP1F, and FAST[15] transcription factor binding sites. # Clinical significance A significant GEO Profile relating to MGC50722 was a study done on male fertility in humans looking at the disease teratozoospermia (GEO Profile ID: 38113951).[13] Teratozoospermia is a condition where during the development of mature sperm cells morphology is altered, thus leading to, in some cases, male infertility.[16] Gene expression shows that in normal human subjects MGC50722 is expressed, while in subjects with teratozoospermia expression levels drop significantly or shut off.	https://www.wikidoc.org/index.php/MGC50722
0934309eec6d3be285eccb2b5f7923e43916cb43	wikidoc	MIR941-1	MIR941-1 MicroRNA 941-1 is a human specific microRNA that is encoded by the MIR941-1 gene. # Function microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. # Evolution The miR-941 gene is only found in humans where it first appeared between one and six million years ago. Its copy number and binding sites have decreased with migration out of Africa. miR-941 regulates genes involved in cellular differentiation and neurotransmitter signalling.	MIR941-1 MicroRNA 941-1 is a human specific microRNA that is encoded by the MIR941-1 gene.[1] # Function microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop.[1] # Evolution The miR-941 gene is only found in humans where it first appeared between one and six million years ago. Its copy number and binding sites have decreased with migration out of Africa. miR-941 regulates genes involved in cellular differentiation and neurotransmitter signalling.[2]	https://www.wikidoc.org/index.php/MIR941-1
e11d899042e985f78fdc1fde3e5d775cf8f568c3	wikidoc	MIS18BP1	MIS18BP1 MIS18 binding protein 1 is a protein that in humans is encoded by the MIS18BP1 gene. The gene is also known as LKNL2, M18BP1, C14orf106, and HSA242977. # Model organisms Model organisms have been used in the study of MIS18BP1 function. A conditional knockout mouse line, called Mis18bp1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and an abnormal tail morphology was observed in female animals.	MIS18BP1 MIS18 binding protein 1 is a protein that in humans is encoded by the MIS18BP1 gene.[1][2][3] The gene is also known as LKNL2, M18BP1, C14orf106, and HSA242977.[1] # Model organisms Model organisms have been used in the study of MIS18BP1 function. A conditional knockout mouse line, called Mis18bp1tm1a(EUCOMM)Wtsi[9] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[10][11][12] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][13] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.[7] Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and an abnormal tail morphology was observed in female animals.[7]	https://www.wikidoc.org/index.php/MIS18BP1
52ea2b12fdf57d694a7f0492c80aeb3b64a41546	wikidoc	MVD tool	MVD tool # Definition of Multivessel Disease For AEGIS-II inclusion criteria #5, multivessel disease criteria can be met by findings on the cardiac catheterization for the index MI, a prior cardiac catheterization, or both: - Index MI cardiac catheterization: 50% or greater stenosis of the left main or at least 2 coronary artery territories (LAD, LCX, RCA) (prior to any interventions performed) - Prior cardiac catheterization: 50% or greater stenosis of left main or at least 2 coronary artery territories (LAD, LCx, RCA) (prior to any interventions performed) - Both: Index MI cardiac catheterization with 1 vessel with 50% or greater stenosis (prior to any interventions performed) AND prior PCI of at least 1 vessel different from index MI vessel - Prior multivessel CABG Multivessel disease requires a 50% or greater stenosis in at least 2 of the 3 major epicardial artery territories (LAD, LCx, RCA) or the left main vessel. Branch vessel disease may qualify as part of the territory of that branch vessel (for example, a diagonal vessel is considered part of the LAD territory). For the purpose of this study, the ramus is considered part of the Left Circumflex artery territory. If a branch vessel is used as a qualifying vessel, that branch should be of large enough size to potentially undergo revascularization if clinically indicated, e.g. >2mm vessel size. # MVD Tool	MVD tool # Definition of Multivessel Disease For AEGIS-II inclusion criteria #5, multivessel disease criteria can be met by findings on the cardiac catheterization for the index MI, a prior cardiac catheterization, or both: - Index MI cardiac catheterization: 50% or greater stenosis of the left main or at least 2 coronary artery territories (LAD, LCX, RCA) (prior to any interventions performed) - Prior cardiac catheterization: 50% or greater stenosis of left main or at least 2 coronary artery territories (LAD, LCx, RCA) (prior to any interventions performed) - Both: Index MI cardiac catheterization with 1 vessel with 50% or greater stenosis (prior to any interventions performed) AND prior PCI of at least 1 vessel different from index MI vessel - Prior multivessel CABG Multivessel disease requires a 50% or greater stenosis in at least 2 of the 3 major epicardial artery territories (LAD, LCx, RCA) or the left main vessel. Branch vessel disease may qualify as part of the territory of that branch vessel (for example, a diagonal vessel is considered part of the LAD territory). For the purpose of this study, the ramus is considered part of the Left Circumflex artery territory. If a branch vessel is used as a qualifying vessel, that branch should be of large enough size to potentially undergo revascularization if clinically indicated, e.g. >2mm vessel size. # MVD Tool	https://www.wikidoc.org/index.php/MVD_tool
0ced4f6f3f2fa5ac5e01b2535f06d18b146539e4	wikidoc	Macrogol	Macrogol Macrogol is the International Nonproprietary Name (INN) for polyethylene glycol. Macrogols have been used as laxatives, i.e. to treat constipation. They are also used as excipients in pharmaceutical products where lower molecular weight variants are used as solvents in oral liquids and soft capsules. Solid variants are used as ointment bases, tablet bindings, film coatings and lubricants. Popular types include: - macrogol 3350 - macrogol 4000 - macrogol 6000 The number represents the average molecular weight of the polyethylene glycol. Combining different molecular weights provides some control over the consistency. - Polyethylene glycol # Available forms Macrogol (polyethylene glycol) is sold as non-prescription preparation in powder form under trade names SoftLax, Purelax, Miralax, Glycoprep, Movicol, Macrogol (generic), Cololyt and Osmolax, among others. It is dissolved in a glass of water to create a clear, tasteless and odorless solution and is swallowed.	Macrogol Macrogol is the International Nonproprietary Name (INN) for polyethylene glycol. Macrogols have been used as laxatives, i.e. to treat constipation.[1] They are also used as excipients in pharmaceutical products where lower molecular weight variants are used as solvents in oral liquids and soft capsules. Solid variants are used as ointment bases, tablet bindings, film coatings and lubricants.[2] Popular types include: - macrogol 3350[3] - macrogol 4000[4] - macrogol 6000[5] The number represents the average molecular weight of the polyethylene glycol. Combining different molecular weights provides some control over the consistency.[2] - Polyethylene glycol # Available forms Macrogol (polyethylene glycol) is sold as non-prescription preparation in powder form under trade names SoftLax, Purelax, Miralax, Glycoprep, Movicol, Macrogol (generic), Cololyt and Osmolax, among others. It is dissolved in a glass of water to create a clear, tasteless and odorless solution and is swallowed.	https://www.wikidoc.org/index.php/Macrogol
fe5238c937e95c6fe37eb50cb05e70e48633a38d	wikidoc	Nutrient	Nutrient # Overview A nutrient is a substance used in an organism's metabolism or physiology which must be taken in from the environment. Non-autotrophic organisms typically acquire nutrients by the ingestion of foods. Methods for nutrient intake vary, with animals and protists having an internal digestive system, while plants digest nutrients externally and then ingested. Organic nutrients include carbohydrates, fats, proteins (or their building blocks, amino acids), and vitamins. Inorganic chemical compounds such as minerals; water, oxygen, and carbon dioxide may also be considered nutrients. A nutrient is essential to an organism if it cannot be synthesized by the organism in sufficient quantities and must be obtained from an external source. Nutrients needed in relatively large quantities are called macronutrients and those needed in relatively small quantities are called micronutrients. See healthy diet for information on the role of nutrients in human nutrition. # Types of human nutrients Macronutrients are defined in several different ways. - The chemical elements humans consume in the largest quantities are carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. - The classes of chemical compounds humans consume in the largest quantities and which provide bulk energy are carbohydrates, proteins, and fats. Water and atmospheric oxygen also must be consumed in large quantities, but are not always considered "food" or "nutrients". - Calcium, salt (sodium and chloride), magnesium, and potassium (along with phosphorus and sulfur) are sometimes added to the list of macronutrients because they are required in relatively large quantities compared to other vitamins and minerals. They are sometimes referred to as the macrominerals. The remaining vitamins, minerals, or elements, are called micronutrients because they are required in relatively small quantities. ## Substances that provide energy - Carbohydrates are compounds made up of sugars. Carbohydrates are classified by their number of sugar units: monosaccharides (such as glucose and fructose), disaccharides (such as sucrose and lactose), oligosaccharides, and polysaccharides (such as starch, glycogen, and cellulose). - Proteins are organic compounds that consists of the amino acids joined by peptide bonds. The body cannot manufacture some of the amino acids (termed essential amino acids); the diet must supply these. In nutrition, proteins are broken down through digestion by proteases back into free amino acids. - Fats consist of a glycerin molecule with three fatty acids attached. Fatty acids are unbranched hydrocarbon chains, connected by single bonds alone (saturated fatty acids) or by both double and single bonds (unsaturated fatty acids). Fats are needed to keep cell membranes functioning properly, to insulate body organs against shock, to keep body temperature stable, and to maintain healthy skin and hair. The body does not manufacture certain fatty acids (termed essential fatty acids) and the diet must supply these. Fat has an energy content of 9 kcal/g (~37.7 kJ/g); proteins and carbohydrates 4 kcal/g (~16.7 kJ/g). Ethanol (grain alcohol) has an energy content of 7 kcal/g (~29.3 kJ/g). ## Substances that support metabolism - Dietary minerals are generally trace elements, salts, or ions such as copper and iron. Some of these minerals are essential to human metabolism. - Vitamins are organic compounds essential to the body. They usually act as coenzymes or cofactors for various proteins in the body. - Water is an essential nutrient and is the solvent in which all the chemical reactions of life take place. - Life is pointless without nutrients # Nutrients and plants The chemical elements consumed in the greatest quantities by plants are carbon, hydrogen, and oxygen. These are present in the environment in the form of water and carbon dioxide; energy is provided by sunlight. Nitrogen, phosphorus, potassium, and sulfur are also needed in relatively large quantities. Together, these are the elemental macronutrients for plants, often represented by the acronym CHNOPS. Usually they are sourced from inorganic (e.g. carbon dioxide, water, nitrate, phosphate, sulphate) or organic (e.g. carbohydrates, lipids, proteins) compounds, although elemental diatomic molecules of nitrogen and (especially) oxygen are often used. Other chemical elements are also necessary to carry out various life processes and build structures; see fertilizer and micronutrient for more information. Some of these are considered macronutrients in certain organisms. The acronym C. HOPKiN'S CaFe Mg (to be used as C. Hopkins coffee mug) is used by some students to remember the list as: Carbon, Hydrogen, Oxygen, Phosphorus, Potassium (K), Nitrogen, Sulfur, Calcium, Iron (Fe), and Magnesium (Mg). Silicon, chloride, sodium, copper, zinc, and molybdenum are sometimes also included, but are in other cases considered micronutrients. Oversupply of plant nutrients in the environment can cause excessive plant and algae growth. Eutrophication, as this process is called, may cause imblances in population numbers and other nutrients that can be harmful to certain species. For example, an algal bloom can deplete the oxygen available for fish to breathe. Causes include water pollution from sewage or runoff from farms (carrying excess agricultural fertilizer). Nitrogen and phosphorus are most commonly the limiting factor in growth, and thus the most likely to trigger eutrophication when introduced artificially. # Essential and non-essential nutrients Nutrients are frequently categorized as essential or nonessential. Essential nutrients are unable to be synthesized internally (either at all, or in sufficient quantities), and so must be consumed by an organism from its environment. For humans, these include essential fatty acids, essential amino acids, vitamins, and certain dietary minerals. Oxygen and water are also essential for human survival, but are generally not considered "food" when consumed in isolation. Humans can derive energy from a wide variety of fats, carbohydrates, proteins, and ethanol, and can synthesize other needed amnio acids from the essential nutrients. Non-essential nutrients can still have a significant impact on health, whether beneficial or toxic. For example, most dietary fiber is not absorbed by the human digestive tract, but is important in digestion and absorption of otherwise harmful substances. Interest has recently increased in phytochemicals, which include many non-essential nutrients which may have health benefits.	Nutrient # Overview A nutrient is a substance used in an organism's metabolism or physiology which must be taken in from the environment. Non-autotrophic organisms typically acquire nutrients by the ingestion of foods. Methods for nutrient intake vary, with animals and protists having an internal digestive system, while plants digest nutrients externally and then ingested. Organic nutrients include carbohydrates, fats, proteins (or their building blocks, amino acids), and vitamins. Inorganic chemical compounds such as minerals; water, oxygen, and carbon dioxide may also be considered nutrients. A nutrient is essential to an organism if it cannot be synthesized by the organism in sufficient quantities and must be obtained from an external source. Nutrients needed in relatively large quantities are called macronutrients and those needed in relatively small quantities are called micronutrients. See healthy diet for information on the role of nutrients in human nutrition. # Types of human nutrients Macronutrients are defined in several different ways. - The chemical elements humans consume in the largest quantities are carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. - The classes of chemical compounds humans consume in the largest quantities and which provide bulk energy are carbohydrates, proteins, and fats. Water and atmospheric oxygen also must be consumed in large quantities, but are not always considered "food" or "nutrients". - Calcium, salt (sodium and chloride), magnesium, and potassium (along with phosphorus and sulfur) are sometimes added to the list of macronutrients because they are required in relatively large quantities compared to other vitamins and minerals. They are sometimes referred to as the macrominerals. The remaining vitamins, minerals, or elements, are called micronutrients because they are required in relatively small quantities. ## Substances that provide energy - Carbohydrates are compounds made up of sugars. Carbohydrates are classified by their number of sugar units: monosaccharides (such as glucose and fructose), disaccharides (such as sucrose and lactose), oligosaccharides, and polysaccharides (such as starch, glycogen, and cellulose). - Proteins are organic compounds that consists of the amino acids joined by peptide bonds. The body cannot manufacture some of the amino acids (termed essential amino acids); the diet must supply these. In nutrition, proteins are broken down through digestion by proteases back into free amino acids. - Fats consist of a glycerin molecule with three fatty acids attached. Fatty acids are unbranched hydrocarbon chains, connected by single bonds alone (saturated fatty acids) or by both double and single bonds (unsaturated fatty acids). Fats are needed to keep cell membranes functioning properly, to insulate body organs against shock, to keep body temperature stable, and to maintain healthy skin and hair. The body does not manufacture certain fatty acids (termed essential fatty acids) and the diet must supply these. Fat has an energy content of 9 kcal/g (~37.7 kJ/g); proteins and carbohydrates 4 kcal/g (~16.7 kJ/g). Ethanol (grain alcohol) has an energy content of 7 kcal/g (~29.3 kJ/g). ## Substances that support metabolism - Dietary minerals are generally trace elements, salts, or ions such as copper and iron. Some of these minerals are essential to human metabolism. - Vitamins are organic compounds essential to the body. They usually act as coenzymes or cofactors for various proteins in the body. - Water is an essential nutrient and is the solvent in which all the chemical reactions of life take place. - Life is pointless without nutrients # Nutrients and plants The chemical elements consumed in the greatest quantities by plants are carbon, hydrogen, and oxygen. These are present in the environment in the form of water and carbon dioxide; energy is provided by sunlight. Nitrogen, phosphorus, potassium, and sulfur are also needed in relatively large quantities. Together, these are the elemental macronutrients for plants, often represented by the acronym CHNOPS. Usually they are sourced from inorganic (e.g. carbon dioxide, water, nitrate, phosphate, sulphate) or organic (e.g. carbohydrates, lipids, proteins) compounds, although elemental diatomic molecules of nitrogen and (especially) oxygen are often used. Other chemical elements are also necessary to carry out various life processes and build structures; see fertilizer and micronutrient for more information. Some of these are considered macronutrients in certain organisms. The acronym C. HOPKiN'S CaFe Mg (to be used as C. Hopkins coffee mug) is used by some students to remember the list as: Carbon, Hydrogen, Oxygen, Phosphorus, Potassium (K), Nitrogen, Sulfur, Calcium, Iron (Fe), and Magnesium (Mg). Silicon, chloride, sodium, copper, zinc, and molybdenum are sometimes also included, but are in other cases considered micronutrients. Oversupply of plant nutrients in the environment can cause excessive plant and algae growth. Eutrophication, as this process is called, may cause imblances in population numbers and other nutrients that can be harmful to certain species. For example, an algal bloom can deplete the oxygen available for fish to breathe. Causes include water pollution from sewage or runoff from farms (carrying excess agricultural fertilizer). Nitrogen and phosphorus are most commonly the limiting factor in growth, and thus the most likely to trigger eutrophication when introduced artificially. # Essential and non-essential nutrients Nutrients are frequently categorized as essential or nonessential. Essential nutrients are unable to be synthesized internally (either at all, or in sufficient quantities), and so must be consumed by an organism from its environment. For humans, these include essential fatty acids, essential amino acids, vitamins, and certain dietary minerals. Oxygen and water are also essential for human survival, but are generally not considered "food" when consumed in isolation. Humans can derive energy from a wide variety of fats, carbohydrates, proteins, and ethanol, and can synthesize other needed amnio acids from the essential nutrients. Non-essential nutrients can still have a significant impact on health, whether beneficial or toxic. For example, most dietary fiber is not absorbed by the human digestive tract, but is important in digestion and absorption of otherwise harmful substances. Interest has recently increased in phytochemicals, which include many non-essential nutrients which may have health benefits.	https://www.wikidoc.org/index.php/Macronutrient_(nutrition)
ca6c15edb8c8371bafa1820c5c567427ebbe070c	wikidoc	Mafenide	Mafenide # 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 Mafenide is an antibacterial that is FDA approved for the treatment of burns. Common adverse reactions include application site reaction. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Mafenide Acetate,USP For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. - The grafted area should be covered with one layer of fine mesh gauze. An eight-ply burn dressing should be cut to the size of the graft and wetted with Mafenide Acetate ,USP for 5% solution using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the burn dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6–8 hours or as necessary to keep wet. - Wound dressings may be left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure. - If allergic manifestations occur during treatment with Mafenide Acetate ,USP for 5% solution, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance. Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mafenide in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mafenide in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Mafenide Acetate,USP For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. - The grafted area should be covered with one layer of fine mesh gauze. An eight-ply burn dressing should be cut to the size of the graft and wetted with Mafenide Acetate ,USP for 5% solution using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the burn dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6–8 hours or as necessary to keep wet. - Wound dressings may be left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure. - If allergic manifestations occur during treatment with Mafenide Acetate ,USP for 5% solution, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance. Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mafenide in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mafenide in pediatric patients. # Contraindications - Mafenide Acetate ,USP For 5% Topical Solution is contraindicated in patients who are hypersensitive to mafenide acetate. It is not known whether there is cross sensitivity to other sulfonamides. # Warnings - Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with Mafenide Acetate. ### Precautions - Mafenide Acetate and its metabolite, p-carboxybenzenesulfonamide, inhibit carbonic anhydrase, which may result in metabolic acidosis, usually compensated by hyperventilation. In the presence of impaired renal function, high blood levels of Mafenide Acetate and its metabolite may exaggerate the carbonic anhydrase inhibition. Therefore, close monitoring of acid-base balance is necessary, particularly in patients with extensive second-degree or partial thickness burns and in those with pulmonary or renal dysfunction. Some burn patients treated with Mafenide Acetate have also been reported to manifest an unexplained syndrome of masked hyperventilation with resulting respiratory alkalosis (slightly alkaline blood pH, low arterial pCO2, and decreased total CO2); change in arterial pO2 is variable. The etiology and significance of these findings are unknown. - Mafenide Acetate should be used with caution in burn patients with acute renal failure. - Fungal colonization may occur concomitantly with reduction of bacterial growth in the burn wound. However, systemic fungal infection through the infected burn wound is rare. # Adverse Reactions ## Clinical Trials Experience - In the clinical setting of severe burns, it is often difficult to distinguish between an adverse reaction to Mafenide Acetate and burn sequelae. In a clinical study of pediatric patients with acute burns requiring autografts who received Mafenide Acetate,USP for 5% SOLUTION in addition to double antibiotic solution (DAB) wound therapy (neomycin sulfate 40 mg and polymyxin B 200,000 units/ liter), the incidence of rash (4.6%) and itching (2.8%) in the group which received Mafenide Acetate USP For 5% Solution was not different from that experienced with (DAB) dressings alone (5.7% and 1.3%, respectively). - From other clinical settings, a single case of bone marrow depression and a single case of an acute attack of porphyria have been reported following therapy with Mafenide Acetate. Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with mafenide acetate. The following adverse reactions have been reported with topical Mafenide Acetate therapy: Pain or burning sensation, rash and pruritus (often localized to the area covered by the wound dressing), erythema, skin maceration from prolonged wet dressings, facial edema, swelling, hives, blisters, eosinophilia. Tachypnea, hyperventilation, decrease in pCO 2, metabolic acidosis, increase in serum chloride. ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Mafenide in the drug label. # Drug Interactions There is limited information regarding Mafenide Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category C - A teratology study performed in rats using oral doses of up to 600 mg/kg/day revealed no evidence of harm to the fetus due to Mafenide Acetate. There are no adequate data regarding the potential reproductive toxicity of Mafenide Acetate in a non-rodent species, nor are there adequate and well-controlled studies in pregnant women. Mafenide Acetate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mafenide in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mafenide during labor and delivery. ### Nursing Mothers - It is not known whether Mafenide Acetate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Mafenide Acetate, 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 - The safety and effectiveness of Mafenide Acetate,USP For 5% Topical Solution have been established in the age groups 3 months to 16 years. ### Geriatic Use - No studies have been conducted to specifically examine the effects of Mafenide Acetate on burn wounds in geriatric patients. ### Gender There is no FDA guidance on the use of Mafenide with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mafenide with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mafenide in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mafenide in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mafenide in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mafenide in patients who are immunocompromised. # Administration and Monitoring ### Administration - Topical ### Monitoring There is limited information regarding Monitoring of Mafenide in the drug label. # IV Compatibility There is limited information regarding IV Compatibility of Mafenide in the drug label. # Overdosage ## Acute Overdose - Single oral doses of 2000 mg/kg of Mafenide Acetate as a 5% solution did not cause mortality or clinical symptoms of toxicity in rats. ## Chronic Overdose There is limited information regarding Chronic Overdose of Mafenide in the drug label. # Pharmacology ## Mechanism of Action - The mechanism of action of Mafenide is not known, but is different from that of the sulfonamides. Mafenide is not antagonized by pABA, serum, pus or tissue exudates, and there is no correlation between bacterial sensitivities to mafenide and to the sulfonamides. Its activity is not altered by changes in the acidity of the environment. The osmolality of the 5% topical solution is approximately 340 mOsm/kg. ## Structure - Mafenide Acetate, USP is a synthetic antimicrobial agent designated chemically as α-amino- p-toluenesulfonamide monoacetate. It has the following structural formula: - Mafenide Acetate, USP is a white, crystalline powder which is freely soluble in water. - Mafenide Acetate,USP For 5% Topical Solution is provided in packets containing 50 g of sterile Mafenide Acetate to be reconstituted in 1000 mL of Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. After mixing, the solution contains 5% w/v of mafenide acetate. The solution is an antimicrobial preparation suitable for topical administration. The solution is not for injection. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable. ## Pharmacodynamics There is limited information regarding Pharmacodynamics of Mafenide in the drug label. ## Pharmacokinetics - Applied topically, Mafenide Acetate diffuses through devascularized areas. Approximately 80% of a Mafenide Acetate dose is delivered to burned tissue over four hours following topical application of the 5% solution. Following application of Mafenide Acetate cream and solution, peak Mafenide concentrations in human burned skin tissue occur at two and four hours, respectively. Peak tissue concentrations are similar following administration of the solution or cream. Once absorbed, Mafenide is rapidly converted to an inactive metabolite (p-carboxybenzenesulfonamide) which is cleared through the kidneys. Clinical studies have shown that when applied topically to burns as an 11.2% Mafenide Acetate cream, blood levels of the parent drug peaked at 2 hours following application, ranging from 26 to 197 µg/mL for single doses of 14 to 77 g of Mafenide Acetate. Metabolite levels peaked at 3 hours, ranging from 10 to 340 µg/mL. Twenty-four hours after application, combined parent and metabolite blood levels had fallen to pretreatment levels. ## Nonclinical Toxicology - No long-term animal studies have been performed to evaluate the carcinogenic potential of Mafenide Acetate; however, the drug did not induce mutations in L5178Y mouse lymphoma cells at the TK locus. - Animal studies have not been performed to evaluate the potential effects of Mafenide Acetate on fertility. # Clinical Studies There is limited information regarding Clinical Studies of Mafenide in the drug label. # How Supplied - Mafenide Acetate , USP for 5% Topical Solution is available in packets containing 50 g of sterile Mafenide Acetate to be prepared using 1000 mL Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. The packets are supplied as follows: - Carton of five 50 g packets (NDC # 49884-902-78). - Recommended Storage - Packets - Store PACKETS in a dry place at room temperature 15° to 30°C (59° to 86°F). - Prepared Solution - Store SOLUTION at 20° to 25°C (68° to 77°F) with excursions permitted to 15° to 30°C (59° to 86°F). - The solution may be held for up to 28 days if stored in unopened containers. - ONCE A CONTAINER IS OPENED, ANY UNUSED SOLUTION MUST BE DISCARDED WITHIN 48 HOURS. ## Storage There is limited information regarding Mafenide 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 Mafenide in the drug label. # Precautions with Alcohol - Alcohol-Mafenide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - MAFENIDE ACETATE® # Look-Alike Drug Names There is limited information regarding Mafenide Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	Mafenide Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, 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. # Overview Mafenide is an antibacterial that is FDA approved for the treatment of burns. Common adverse reactions include application site reaction. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Mafenide Acetate,USP For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. - The grafted area should be covered with one layer of fine mesh gauze. An eight-ply burn dressing should be cut to the size of the graft and wetted with Mafenide Acetate ,USP for 5% solution using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the burn dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6–8 hours or as necessary to keep wet. - Wound dressings may be left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure. - If allergic manifestations occur during treatment with Mafenide Acetate ,USP for 5% solution, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance. Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mafenide in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mafenide in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Mafenide Acetate,USP For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. - The grafted area should be covered with one layer of fine mesh gauze. An eight-ply burn dressing should be cut to the size of the graft and wetted with Mafenide Acetate ,USP for 5% solution using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the burn dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6–8 hours or as necessary to keep wet. - Wound dressings may be left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure. - If allergic manifestations occur during treatment with Mafenide Acetate ,USP for 5% solution, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance. Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mafenide in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Mafenide in pediatric patients. # Contraindications - Mafenide Acetate ,USP For 5% Topical Solution is contraindicated in patients who are hypersensitive to mafenide acetate. It is not known whether there is cross sensitivity to other sulfonamides. # Warnings - Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with Mafenide Acetate. ### Precautions - Mafenide Acetate and its metabolite, p-carboxybenzenesulfonamide, inhibit carbonic anhydrase, which may result in metabolic acidosis, usually compensated by hyperventilation. In the presence of impaired renal function, high blood levels of Mafenide Acetate and its metabolite may exaggerate the carbonic anhydrase inhibition. Therefore, close monitoring of acid-base balance is necessary, particularly in patients with extensive second-degree or partial thickness burns and in those with pulmonary or renal dysfunction. Some burn patients treated with Mafenide Acetate have also been reported to manifest an unexplained syndrome of masked hyperventilation with resulting respiratory alkalosis (slightly alkaline blood pH, low arterial pCO2, and decreased total CO2); change in arterial pO2 is variable. The etiology and significance of these findings are unknown. - Mafenide Acetate should be used with caution in burn patients with acute renal failure. - Fungal colonization may occur concomitantly with reduction of bacterial growth in the burn wound. However, systemic fungal infection through the infected burn wound is rare. # Adverse Reactions ## Clinical Trials Experience - In the clinical setting of severe burns, it is often difficult to distinguish between an adverse reaction to Mafenide Acetate and burn sequelae. In a clinical study of pediatric patients with acute burns requiring autografts who received Mafenide Acetate,USP for 5% SOLUTION in addition to double antibiotic solution (DAB) wound therapy (neomycin sulfate 40 mg and polymyxin B 200,000 units/ liter), the incidence of rash (4.6%) and itching (2.8%) in the group which received Mafenide Acetate USP For 5% Solution was not different from that experienced with (DAB) dressings alone (5.7% and 1.3%, respectively). - From other clinical settings, a single case of bone marrow depression and a single case of an acute attack of porphyria have been reported following therapy with Mafenide Acetate. Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with mafenide acetate. The following adverse reactions have been reported with topical Mafenide Acetate therapy: Pain or burning sensation, rash and pruritus (often localized to the area covered by the wound dressing), erythema, skin maceration from prolonged wet dressings, facial edema, swelling, hives, blisters, eosinophilia. Tachypnea, hyperventilation, decrease in pCO 2, metabolic acidosis, increase in serum chloride. ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Mafenide in the drug label. # Drug Interactions There is limited information regarding Mafenide Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category C - A teratology study performed in rats using oral doses of up to 600 mg/kg/day revealed no evidence of harm to the fetus due to Mafenide Acetate. There are no adequate data regarding the potential reproductive toxicity of Mafenide Acetate in a non-rodent species, nor are there adequate and well-controlled studies in pregnant women. Mafenide Acetate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mafenide in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mafenide during labor and delivery. ### Nursing Mothers - It is not known whether Mafenide Acetate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Mafenide Acetate, 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 - The safety and effectiveness of Mafenide Acetate,USP For 5% Topical Solution have been established in the age groups 3 months to 16 years. ### Geriatic Use - No studies have been conducted to specifically examine the effects of Mafenide Acetate on burn wounds in geriatric patients. ### Gender There is no FDA guidance on the use of Mafenide with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mafenide with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mafenide in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mafenide in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mafenide in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mafenide in patients who are immunocompromised. # Administration and Monitoring ### Administration - Topical ### Monitoring There is limited information regarding Monitoring of Mafenide in the drug label. # IV Compatibility There is limited information regarding IV Compatibility of Mafenide in the drug label. # Overdosage ## Acute Overdose - Single oral doses of 2000 mg/kg of Mafenide Acetate as a 5% solution did not cause mortality or clinical symptoms of toxicity in rats. ## Chronic Overdose There is limited information regarding Chronic Overdose of Mafenide in the drug label. # Pharmacology ## Mechanism of Action - The mechanism of action of Mafenide is not known, but is different from that of the sulfonamides. Mafenide is not antagonized by pABA, serum, pus or tissue exudates, and there is no correlation between bacterial sensitivities to mafenide and to the sulfonamides. Its activity is not altered by changes in the acidity of the environment. The osmolality of the 5% topical solution is approximately 340 mOsm/kg. ## Structure - Mafenide Acetate, USP is a synthetic antimicrobial agent designated chemically as α-amino- p-toluenesulfonamide monoacetate. It has the following structural formula: - Mafenide Acetate, USP is a white, crystalline powder which is freely soluble in water. - Mafenide Acetate,USP For 5% Topical Solution is provided in packets containing 50 g of sterile Mafenide Acetate to be reconstituted in 1000 mL of Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. After mixing, the solution contains 5% w/v of mafenide acetate. The solution is an antimicrobial preparation suitable for topical administration. The solution is not for injection. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable. ## Pharmacodynamics There is limited information regarding Pharmacodynamics of Mafenide in the drug label. ## Pharmacokinetics - Applied topically, Mafenide Acetate diffuses through devascularized areas. Approximately 80% of a Mafenide Acetate dose is delivered to burned tissue over four hours following topical application of the 5% solution. Following application of Mafenide Acetate cream and solution, peak Mafenide concentrations in human burned skin tissue occur at two and four hours, respectively. Peak tissue concentrations are similar following administration of the solution or cream. Once absorbed, Mafenide is rapidly converted to an inactive metabolite (p-carboxybenzenesulfonamide) which is cleared through the kidneys. Clinical studies have shown that when applied topically to burns as an 11.2% Mafenide Acetate cream, blood levels of the parent drug peaked at 2 hours following application, ranging from 26 to 197 µg/mL for single doses of 14 to 77 g of Mafenide Acetate. Metabolite levels peaked at 3 hours, ranging from 10 to 340 µg/mL. Twenty-four hours after application, combined parent and metabolite blood levels had fallen to pretreatment levels. ## Nonclinical Toxicology - No long-term animal studies have been performed to evaluate the carcinogenic potential of Mafenide Acetate; however, the drug did not induce mutations in L5178Y mouse lymphoma cells at the TK locus. - Animal studies have not been performed to evaluate the potential effects of Mafenide Acetate on fertility. # Clinical Studies There is limited information regarding Clinical Studies of Mafenide in the drug label. # How Supplied - Mafenide Acetate , USP for 5% Topical Solution is available in packets containing 50 g of sterile Mafenide Acetate to be prepared using 1000 mL Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. The packets are supplied as follows: - Carton of five 50 g packets (NDC # 49884-902-78). - Recommended Storage - Packets - Store PACKETS in a dry place at room temperature 15° to 30°C (59° to 86°F). - Prepared Solution - Store SOLUTION at 20° to 25°C (68° to 77°F) with excursions permitted to 15° to 30°C (59° to 86°F). - The solution may be held for up to 28 days if stored in unopened containers. - ONCE A CONTAINER IS OPENED, ANY UNUSED SOLUTION MUST BE DISCARDED WITHIN 48 HOURS. ## Storage There is limited information regarding Mafenide 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 Mafenide in the drug label. # Precautions with Alcohol - Alcohol-Mafenide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - MAFENIDE ACETATE®[1] # Look-Alike Drug Names There is limited information regarding Mafenide Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	https://www.wikidoc.org/index.php/Mafenide
e7779b7bf290daff084422c100207f000e219c89	wikidoc	Mannitol	Mannitol # 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 Mannitol is a osmotic diuretic that is FDA approved for the treatment of oliguric phase of acute renal failure, cerebral edema, and elevated intraocular pressure. Mannitol is also indicated for promoting the urinary excretion of toxic substances. Common adverse reactions include nausea, vomiting, rhinitis, skin necrosis, thrombophlebitis, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever, and angina-like chest pains. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Mannitol should be administered only by intravenous infusion. The total dosage, concentration, and rate of administration should be governed by the nature and severity of the condition being treated, fluid requirement, and urinary output. - The usual adult dosage ranges from 20 to 100 g in a 24 hour period, but in most instances an adequate response will be achieved at a dosage of approximately 50 to 100 g in a 24 hour period. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 mL/hour. This outline of administration and dosage is only a general guide to therapy. - Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible. - Test Dose: A test dose of mannitol should be given prior to instituting Mannitol therapy for patients with marked oliguria, or those believed to have inadequate renal function. Such a test dose may be approximately 0.2 g/kg body weight (about 75 mL of a 20% solution or 100 mL of a 15% solution) infused in a period of three to five minutes to produce a urine flow of at least 30 to 50 mL/hour. If urine flow does not increase, a second test dose may be given; if there is an inadequate response, the patient should be reevaluated. - Measurement of glomerular filtration rate by creatinine clearance may be useful for determination of dosage. - Dosing Information - When used during cardiovascular and other types of surgery, 50 to 100 g of mannitol as a 5, 10, or 15% solution may be given. The concentration will depend upon the fluid requirements of the patient. - Dosing Information - The usual dose for treatment of oliguria is 100 g administered as a 15 or 20% solution. - Dosing Information - A dose of 1.5 to 2.0 g/kg as a 20% solution (7.5 to 10 mL/kg) or as a 15% solution (10 to 13 mL/kg) may be given over a period as short as 30 minutes in order to obtain a prompt and maximal effect. When used preoperatively the dose should be given one to one and one-half hours before surgery to achieve maximal reduction of intraocular pressure before operation. - Dosing Information - Usually a maximum reduction in intracranial pressure in adults can be achieved with a dose of 0.25 g/kg given not more frequently than every six to eight hours. An osmotic gradient between the blood and cerebrospinal fluid of approximately 10 mOsmol will yield a satisfactory reduction in intracranial pressure. - Dosing Information - As an agent to promote diuresis in intoxications, 5%, 10%, 15% or 20% mannitol is indicated. The concentration will depend upon the fluid requirement and urinary output of the patient. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mannitol in adult patients. ### Non–Guideline-Supported Use - Dosing Information - 9 mosm/kg - Dosing Information - 10 mL (2.5 g) as a 25% solution over 30 to 60 seconds - Dosing Information - 0.6 to 0.7 g/kg # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Safety and effectiveness in children below the age of 12 have not been established. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mannitol in pediatric patients. ### Non–Guideline-Supported Use - Dosing Information - 40 g/m2 over 1 hour orally as a 5.5% or a 20% solution # Contraindications - Well established anuria due to severe renal disease - Severe pulmonary congestion or frank pulmonary edema - Active intracranial bleeding except during craniotomy - Severe dehydration - Progressive renal damage or dysfunction after institution of mannitol therapy, including increasing oliguria and azotemia - Progressive heart failure or pulmonary congestion after institution of mannitol therapy # Warnings - In patients with severe impairment of renal function, a test dose should be utilized (see Dosage and Administration). A second test dose may be tried if there is an inadequate response, but no more than two test doses should be attempted. - The obligatory diuretic response following rapid infusion of 15% or 20% mannitol injection may further aggravate preexisting hemoconcentration. Excessive loss of water and electrolytes may lead to serious imbalances. Serum sodium and potassium should be carefully monitored during mannitol administration. - If urine output continues to decline during mannitol infusion, the patient’s clinical status should be closely reviewed and mannitol infusion suspended if necessary. Accumulation of mannitol may result in overexpansion of the extracellular fluid which may intensify existing or latent congestive heart failure. - Excessive loss of water and electrolytes may lead to serious imbalances. With continued administration of mannitol, loss of water in excess of electrolytes can cause hypernatremia. Electrolyte measurements, including sodium and potassium, are therefore, of vital importance in monitoring the infusion of mannitol. - Osmotic nephrosis, a reversible vacuolization of the tubules of unknown clinical significance, may proceed to severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion. ### Precautions - The cardiovascular status of the patient should be carefully evaluated before rapidly administering mannitol since sudden expansion of the extracellular fluid may lead to fulminating congestive heart failure. - Shift of sodium free intracellular fluid into the extracellular compartment following mannitol infusion may lower serum sodium concentration and aggravate preexisting hyponatremia. - By sustaining diuresis, mannitol administration may obscure and intensify inadequate hydration or hypovolemia. - Electrolyte free mannitol injections should not be given conjointly with blood. If it is essential that blood be given simultaneously, at least 20 mEq of sodium chloride should be added to each liter of mannitol solution to avoid pseudoagglutination. - When exposed to low temperatures, solutions of mannitol may crystallize. Concentrations greater than 15% have a greater tendency to crystallization. Inspect for crystals prior to administration. If crystals are visible, redissolve by warming the solution up to 70°C, with agitation. Allow the solution to cool to room temperature before reinspection for crystals. Administer intravenously using sterile, filter-type administration set. - Although blood levels of mannitol can be measured, there is little if any clinical virtue in doing so. The appropriate monitoring of blood levels of sodium and potassium; degree of hemoconcentration or hemodilution, if any; indices of renal, cardiac and pulmonary function are paramount in avoiding excessive fluid and electrolyte shifts. The routine features of physical examination and clinical chemistries suffice in achieving an adequate degree of appropriate patient monitoring. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Clinical Trial Experience of Mannitol in the drug label. ## Postmarketing Experience - Extensive use of mannitol over the last several decades has produced recorded adverse events, in a variety of clinical settings, that are isolated or idiosyncratic in nature. None of these adverse reactions have occurred with any great frequency nor with any security in attributing them to mannitol. - The inability to clearly exclude the drug related nature of such events in these isolated reports prompts the necessity to list the reactions that have been observed in patients during or following mannitol infusion. In this fashion, patients have exhibited nausea, vomiting, rhinitis, local pain, skin necrosis and thrombophlebitis at the site of injection, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever and angina-like chest pains. - Of far greater clinical significance is a variety of events that are related to inappropriate recognition and monitoring of fluid shifts. These are not intrinsic adverse reactions to the drug but the consequence of manipulating osmolarity by any agency in a therapeutically inappropriate manner. Failure to recognize severe impairment of renal function with the high likelihood of nondiuretic response can lead to aggravated dehydration of tissues and increased vascular fluid load. Induced diuresis in the presence of preexisting hemoconcentration and preexisting deficiency of water and electrolytes can lead to serious imbalances. Expansion of the extracellular space can aggravate cardiac decompensation or induce it in the presence of latent heart failure. Pulmonary congestion or edema can be seriously aggravated with the expansion of the extracellular and therefore intravascular fluid load. Hemodilution and dilution of the extracellular fluid space by osmotic shift of water can induce or aggravate preexisting hyponatremia. - If unrecognized, such fluid and/or electrolyte shift can produce the reported adverse reactions of pulmonary congestion, acidosis, electrolyte loss, dryness of mouth, thirst, edema, headache, blurred vision, convulsions and congestive cardiac failure. - These are not truly adverse reactions to the drug and can be appropriately prevented by evaluation of degree of renal failure with a test dose response to mannitol when indicated; evaluation of hypervolemia and hypovolemia; sodium and potassium levels; hemodilution or hemoconcentration; and evaluation of renal, cardiac and pulmonary function at the onset of therapy. # Drug Interactions There is limited information regarding Drug Interactions of Mannitol in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category C - Animal reproduction studies have not been conducted with mannitol. It is also not known whether mannitol can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mannitol should be given to a pregnant woman 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 Mannitol in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mannitol during labor and delivery. ### Nursing Mothers - It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mannitol is administered to a nursing woman. ### Pediatric Use - Safety and effectiveness in children below the age of 12 have not been established. ### Geriatic Use - Clinical studies of Osmitrol Injection (Mannitol Injection, USP) did not include sufficient numbers 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. ### Gender There is no FDA guidance on the use of Mannitol with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mannitol with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mannitol in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mannitol in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mannitol in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mannitol in patients who are immunocompromised. # Administration and Monitoring ### Administration - Oral - Intravenous ### Monitoring - Electrolyte measurements, including sodium and potassium are of vital importance in monitoring the infusion of mannitol. - Osmotic nephrosis, a reversible vacuolization of the tubules of unknown clinical significance, may proceed to severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion. # IV Compatibility There is limited information regarding IV Compatibility of Mannitol in the drug label. # Overdosage ## Acute Overdose There is limited information regarding Acute Overdose of Mannitol in the drug label. ## Chronic Overdose There is limited information regarding Chronic Overdose of Mannitol in the drug label. # Pharmacology ## Mechanism of Action - Osmitrol Injection (Mannitol Injection, USP) is one of the nonelectrolyte, obligatory, osmotic diuretics. It is freely filterable at the renal glomerulus, only poorly reabsorbed by the renal tubule, not secreted by the tubule, and is pharmacologically inert. ## Structure - Osmitrol Injection (Mannitol Injection, USP) is a sterile, nonpyrogenic solution of Mannitol, USP in a single dose container for intravenous administration. It contains no antimicrobial agents. Mannitol is a six carbon sugar alcohol prepared commercially by the reduction of dextrose. Although virtually inert metabolically in humans, it occurs naturally in fruits and vegetables. Mannitol is an obligatory osmotic diuretic. The pH is adjusted with sodium hydroxide or hydrochloric acid. Composition, osmolarity, and pH are shown in Table 1. - The Viaflex plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. ## Pharmacodynamics - Mannitol, when administered intravenously, exerts its osmotic effect as a solute of relatively small molecular size being largely confined to the extracellular space. Only relatively small amounts of the dose administered is metabolized. Mannitol is readily diffused through the glomerulus of the kidney over a wide range of normal and impaired kidney function. In this fashion, approximately 80% of a 100 gram dose of mannitol will appear in the urine in three hours with lesser amounts thereafter. Even at peak concentrations, mannitol will exhibit less than 10% of tubular reabsorption and is not secreted by tubular cells. Mannitol will hinder tubular reabsorption of water and enhance excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate. - This increase in extracellular osmolarity effected by the intravenous administration of mannitol will induce the movement of intracellular water to the extracellular and vascular spaces. This action underlies the role of mannitol in reducing intracranial pressure, intracranial edema, and elevated intraocular pressure. ## Pharmacokinetics There is limited information regarding Pharmacokinetics of Mannitol in the drug label. ## Nonclinical Toxicology There is limited information regarding Nonclinical Toxicology of Mannitol in the drug label. # Clinical Studies There is limited information regarding Clinical Studies of Mannitol in the drug label. # How Supplied - Osmitrol Injection (Mannitol Injection, USP) in Viaflex plastic containers is available as follows: - Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the product be stored at room temperature (25°C); brief exposure up to 40°C does not adversely affect the product. ## Storage There is limited information regarding Mannitol 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 Mannitol in the drug label. # Precautions with Alcohol - Alcohol-Mannitol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Osmitrol® # Look-Alike Drug Names - N/A # Drug Shortage Status # Price	Mannitol Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi # 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 Mannitol is a osmotic diuretic that is FDA approved for the treatment of oliguric phase of acute renal failure, cerebral edema, and elevated intraocular pressure. Mannitol is also indicated for promoting the urinary excretion of toxic substances. Common adverse reactions include nausea, vomiting, rhinitis, skin necrosis, thrombophlebitis, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever, and angina-like chest pains. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Mannitol should be administered only by intravenous infusion. The total dosage, concentration, and rate of administration should be governed by the nature and severity of the condition being treated, fluid requirement, and urinary output. - The usual adult dosage ranges from 20 to 100 g in a 24 hour period, but in most instances an adequate response will be achieved at a dosage of approximately 50 to 100 g in a 24 hour period. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 mL/hour. This outline of administration and dosage is only a general guide to therapy. - Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions, where possible. - Test Dose: A test dose of mannitol should be given prior to instituting Mannitol therapy for patients with marked oliguria, or those believed to have inadequate renal function. Such a test dose may be approximately 0.2 g/kg body weight (about 75 mL of a 20% solution or 100 mL of a 15% solution) infused in a period of three to five minutes to produce a urine flow of at least 30 to 50 mL/hour. If urine flow does not increase, a second test dose may be given; if there is an inadequate response, the patient should be reevaluated. - Measurement of glomerular filtration rate by creatinine clearance may be useful for determination of dosage. - Dosing Information - When used during cardiovascular and other types of surgery, 50 to 100 g of mannitol as a 5, 10, or 15% solution may be given. The concentration will depend upon the fluid requirements of the patient. - Dosing Information - The usual dose for treatment of oliguria is 100 g administered as a 15 or 20% solution. - Dosing Information - A dose of 1.5 to 2.0 g/kg as a 20% solution (7.5 to 10 mL/kg) or as a 15% solution (10 to 13 mL/kg) may be given over a period as short as 30 minutes in order to obtain a prompt and maximal effect. When used preoperatively the dose should be given one to one and one-half hours before surgery to achieve maximal reduction of intraocular pressure before operation. - Dosing Information - Usually a maximum reduction in intracranial pressure in adults can be achieved with a dose of 0.25 g/kg given not more frequently than every six to eight hours. An osmotic gradient between the blood and cerebrospinal fluid of approximately 10 mOsmol will yield a satisfactory reduction in intracranial pressure. - Dosing Information - As an agent to promote diuresis in intoxications, 5%, 10%, 15% or 20% mannitol is indicated. The concentration will depend upon the fluid requirement and urinary output of the patient. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mannitol in adult patients. ### Non–Guideline-Supported Use - Dosing Information - 9 mosm/kg[1][2] - Dosing Information - 10 mL (2.5 g) as a 25% solution over 30 to 60 seconds[3] - Dosing Information - 0.6 to 0.7 g/kg[4] # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Safety and effectiveness in children below the age of 12 have not been established. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Mannitol in pediatric patients. ### Non–Guideline-Supported Use - Dosing Information - 40 g/m2 over 1 hour orally as a 5.5% or a 20% solution[5] # Contraindications - Well established anuria due to severe renal disease - Severe pulmonary congestion or frank pulmonary edema - Active intracranial bleeding except during craniotomy - Severe dehydration - Progressive renal damage or dysfunction after institution of mannitol therapy, including increasing oliguria and azotemia - Progressive heart failure or pulmonary congestion after institution of mannitol therapy # Warnings - In patients with severe impairment of renal function, a test dose should be utilized (see Dosage and Administration). A second test dose may be tried if there is an inadequate response, but no more than two test doses should be attempted. - The obligatory diuretic response following rapid infusion of 15% or 20% mannitol injection may further aggravate preexisting hemoconcentration. Excessive loss of water and electrolytes may lead to serious imbalances. Serum sodium and potassium should be carefully monitored during mannitol administration. - If urine output continues to decline during mannitol infusion, the patient’s clinical status should be closely reviewed and mannitol infusion suspended if necessary. Accumulation of mannitol may result in overexpansion of the extracellular fluid which may intensify existing or latent congestive heart failure. - Excessive loss of water and electrolytes may lead to serious imbalances. With continued administration of mannitol, loss of water in excess of electrolytes can cause hypernatremia. Electrolyte measurements, including sodium and potassium, are therefore, of vital importance in monitoring the infusion of mannitol. - Osmotic nephrosis, a reversible vacuolization of the tubules of unknown clinical significance, may proceed to severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion. ### Precautions - The cardiovascular status of the patient should be carefully evaluated before rapidly administering mannitol since sudden expansion of the extracellular fluid may lead to fulminating congestive heart failure. - Shift of sodium free intracellular fluid into the extracellular compartment following mannitol infusion may lower serum sodium concentration and aggravate preexisting hyponatremia. - By sustaining diuresis, mannitol administration may obscure and intensify inadequate hydration or hypovolemia. - Electrolyte free mannitol injections should not be given conjointly with blood. If it is essential that blood be given simultaneously, at least 20 mEq of sodium chloride should be added to each liter of mannitol solution to avoid pseudoagglutination. - When exposed to low temperatures, solutions of mannitol may crystallize. Concentrations greater than 15% have a greater tendency to crystallization. Inspect for crystals prior to administration. If crystals are visible, redissolve by warming the solution up to 70°C, with agitation. Allow the solution to cool to room temperature before reinspection for crystals. Administer intravenously using sterile, filter-type administration set. - Although blood levels of mannitol can be measured, there is little if any clinical virtue in doing so. The appropriate monitoring of blood levels of sodium and potassium; degree of hemoconcentration or hemodilution, if any; indices of renal, cardiac and pulmonary function are paramount in avoiding excessive fluid and electrolyte shifts. The routine features of physical examination and clinical chemistries suffice in achieving an adequate degree of appropriate patient monitoring. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Clinical Trial Experience of Mannitol in the drug label. ## Postmarketing Experience - Extensive use of mannitol over the last several decades has produced recorded adverse events, in a variety of clinical settings, that are isolated or idiosyncratic in nature. None of these adverse reactions have occurred with any great frequency nor with any security in attributing them to mannitol. - The inability to clearly exclude the drug related nature of such events in these isolated reports prompts the necessity to list the reactions that have been observed in patients during or following mannitol infusion. In this fashion, patients have exhibited nausea, vomiting, rhinitis, local pain, skin necrosis and thrombophlebitis at the site of injection, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever and angina-like chest pains. - Of far greater clinical significance is a variety of events that are related to inappropriate recognition and monitoring of fluid shifts. These are not intrinsic adverse reactions to the drug but the consequence of manipulating osmolarity by any agency in a therapeutically inappropriate manner. Failure to recognize severe impairment of renal function with the high likelihood of nondiuretic response can lead to aggravated dehydration of tissues and increased vascular fluid load. Induced diuresis in the presence of preexisting hemoconcentration and preexisting deficiency of water and electrolytes can lead to serious imbalances. Expansion of the extracellular space can aggravate cardiac decompensation or induce it in the presence of latent heart failure. Pulmonary congestion or edema can be seriously aggravated with the expansion of the extracellular and therefore intravascular fluid load. Hemodilution and dilution of the extracellular fluid space by osmotic shift of water can induce or aggravate preexisting hyponatremia. - If unrecognized, such fluid and/or electrolyte shift can produce the reported adverse reactions of pulmonary congestion, acidosis, electrolyte loss, dryness of mouth, thirst, edema, headache, blurred vision, convulsions and congestive cardiac failure. - These are not truly adverse reactions to the drug and can be appropriately prevented by evaluation of degree of renal failure with a test dose response to mannitol when indicated; evaluation of hypervolemia and hypovolemia; sodium and potassium levels; hemodilution or hemoconcentration; and evaluation of renal, cardiac and pulmonary function at the onset of therapy. # Drug Interactions There is limited information regarding Drug Interactions of Mannitol in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category C - Animal reproduction studies have not been conducted with mannitol. It is also not known whether mannitol can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mannitol should be given to a pregnant woman 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 Mannitol in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Mannitol during labor and delivery. ### Nursing Mothers - It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mannitol is administered to a nursing woman. ### Pediatric Use - Safety and effectiveness in children below the age of 12 have not been established. ### Geriatic Use - Clinical studies of Osmitrol Injection (Mannitol Injection, USP) did not include sufficient numbers 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. ### Gender There is no FDA guidance on the use of Mannitol with respect to specific gender populations. ### Race There is no FDA guidance on the use of Mannitol with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Mannitol in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Mannitol in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Mannitol in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Mannitol in patients who are immunocompromised. # Administration and Monitoring ### Administration - Oral - Intravenous ### Monitoring - Electrolyte measurements, including sodium and potassium are of vital importance in monitoring the infusion of mannitol. - Osmotic nephrosis, a reversible vacuolization of the tubules of unknown clinical significance, may proceed to severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion. # IV Compatibility There is limited information regarding IV Compatibility of Mannitol in the drug label. # Overdosage ## Acute Overdose There is limited information regarding Acute Overdose of Mannitol in the drug label. ## Chronic Overdose There is limited information regarding Chronic Overdose of Mannitol in the drug label. # Pharmacology ## Mechanism of Action - Osmitrol Injection (Mannitol Injection, USP) is one of the nonelectrolyte, obligatory, osmotic diuretics. It is freely filterable at the renal glomerulus, only poorly reabsorbed by the renal tubule, not secreted by the tubule, and is pharmacologically inert. ## Structure - Osmitrol Injection (Mannitol Injection, USP) is a sterile, nonpyrogenic solution of Mannitol, USP in a single dose container for intravenous administration. It contains no antimicrobial agents. Mannitol** is a six carbon sugar alcohol prepared commercially by the reduction of dextrose. Although virtually inert metabolically in humans, it occurs naturally in fruits and vegetables. Mannitol is an obligatory osmotic diuretic. The pH is adjusted with sodium hydroxide or hydrochloric acid. Composition, osmolarity, and pH are shown in Table 1. - The Viaflex plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. ## Pharmacodynamics - Mannitol, when administered intravenously, exerts its osmotic effect as a solute of relatively small molecular size being largely confined to the extracellular space. Only relatively small amounts of the dose administered is metabolized. Mannitol is readily diffused through the glomerulus of the kidney over a wide range of normal and impaired kidney function. In this fashion, approximately 80% of a 100 gram dose of mannitol will appear in the urine in three hours with lesser amounts thereafter. Even at peak concentrations, mannitol will exhibit less than 10% of tubular reabsorption and is not secreted by tubular cells. Mannitol will hinder tubular reabsorption of water and enhance excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate. - This increase in extracellular osmolarity effected by the intravenous administration of mannitol will induce the movement of intracellular water to the extracellular and vascular spaces. This action underlies the role of mannitol in reducing intracranial pressure, intracranial edema, and elevated intraocular pressure. ## Pharmacokinetics There is limited information regarding Pharmacokinetics of Mannitol in the drug label. ## Nonclinical Toxicology There is limited information regarding Nonclinical Toxicology of Mannitol in the drug label. # Clinical Studies There is limited information regarding Clinical Studies of Mannitol in the drug label. # How Supplied - Osmitrol Injection (Mannitol Injection, USP) in Viaflex plastic containers is available as follows: - Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the product be stored at room temperature (25°C); brief exposure up to 40°C does not adversely affect the product. ## Storage There is limited information regarding Mannitol 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 Mannitol in the drug label. # Precautions with Alcohol - Alcohol-Mannitol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Osmitrol®[6] # Look-Alike Drug Names - N/A[7] # Drug Shortage Status # Price	https://www.wikidoc.org/index.php/Mannitol
8c2ee2a622c0f4dae8639406d780db9d124f4e42	wikidoc	Marasmus	Marasmus # Overview Marasmus is a form of severe protein-energy malnutrition characterised by energy deficiency. Some other PEMs are kwashiorkor and cachexia (the most common one in the developed world). A child with marasmus looks emaciated and the body weight may reduce to less than 80% of the normal weight for that height. Marasmus occurrence increases prior to age 1 whereas Kwashiorkor occurrence increases after 18 months. # Causes Marasmus is caused by failure to take in sufficient calories. # Signs The signs of common characteristics of protein-energy malnutrition: dry skin, loose skin folds hanging over the glutei, axillae, etc. Drastic loss of adipose tissue from normal areas of fat deposits like buttocks and thighs. The afflicted are often fretful, irritable, and voraciously hungry. There may be alternate bands of pigmented and depigmented hair (flag sign), or flaky paint appearance of skin due to peeling. # Treatment It is essential to treat not only the symptoms but also the complications of the disorder like infections, dehydration and circulation disorders, which are frequently lethal and lead to high mortality if ignored. Ultimately marasmus progresses to the point of no return when the body's machinery for protein synthesis, itself made of protein, has been degraded. At this point, attempts to correct the situation by giving food or protein fail to prevent death.	Marasmus Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: # Overview Marasmus is a form of severe protein-energy malnutrition characterised by energy deficiency. Some other PEMs are kwashiorkor and cachexia (the most common one in the developed world). A child with marasmus looks emaciated and the body weight may reduce to less than 80% of the normal weight for that height. Marasmus occurrence increases prior to age 1 whereas Kwashiorkor occurrence increases after 18 months. # Causes Marasmus is caused by failure to take in sufficient calories. # Signs The signs of common characteristics of protein-energy malnutrition: dry skin, loose skin folds hanging over the glutei, axillae, etc. Drastic loss of adipose tissue from normal areas of fat deposits like buttocks and thighs. The afflicted are often fretful, irritable, and voraciously hungry. There may be alternate bands of pigmented and depigmented hair (flag sign), or flaky paint appearance of skin due to peeling. # Treatment It is essential to treat not only the symptoms but also the complications of the disorder like infections, dehydration and circulation disorders, which are frequently lethal and lead to high mortality if ignored. Ultimately marasmus progresses to the point of no return when the body's machinery for protein synthesis, itself made of protein, has been degraded. At this point, attempts to correct the situation by giving food or protein fail to prevent death.	https://www.wikidoc.org/index.php/Marasmic
cd345f64f2605015121ee66297a4df6a17aa212e	wikidoc	Marjoram	Marjoram Marjoram (Origanum majorana, Lamiaceae) is a somewhat cold-sensitive perennial herb or undershrub with sweet pine and citrus flavours. It is also called Sweet Marjoram or Knotted Marjoram and Majorana hortensis. The name marjoram (Old French majorane, Medieval Latin majorana) does not directly derive from the Latin word maior (major). Marjoram is cultivated for its aromatic leaves, either green or dry, for culinary purposes; the tops are cut as the plants begin to flower and are dried slowly in the shade. It is often used in herb combinations such as Herbes de Provence and Za'atar. Although considered cold-sensitive, marjoram can sometimes prove hardy even in zone 5. ## Related species Oregano (Origanum vulgare, sometimes listed with Marjoram as Origanum majorana) is also called Wild Marjoram. It is a perennial common in southern Europe in dry copses and on hedge-banks, with many stout stems 30-80 cm high, bearing short-stalked somewhat ovate leaves and clusters of purple flowers. It has a stronger flavor and a more penetrating quality. Pot Marjoram or Cretan Oregano (Origanum onites) has similar uses to marjoram. Hardy Marjoram or Italian marjoram is a cross of marjoram with oregano that is much more resistant to cold, but is slightly less sweet. Origanum pulchellum, Showy Marjoram or Showy Oregano. (Catalan marduix; Spanish mejorana) # Surname Marjoram is a surname.	Marjoram Marjoram (Origanum majorana, Lamiaceae) is a somewhat cold-sensitive perennial herb or undershrub with sweet pine and citrus flavours. It is also called Sweet Marjoram or Knotted Marjoram and Majorana hortensis. The name marjoram (Old French majorane, Medieval Latin majorana) does not directly derive from the Latin word maior (major).[1] Marjoram is cultivated for its aromatic leaves, either green or dry, for culinary purposes; the tops are cut as the plants begin to flower and are dried slowly in the shade. It is often used in herb combinations such as Herbes de Provence and Za'atar. Although considered cold-sensitive, marjoram can sometimes prove hardy even in zone 5. ## Related species Oregano (Origanum vulgare, sometimes listed with Marjoram as Origanum majorana) is also called Wild Marjoram. It is a perennial common in southern Europe in dry copses and on hedge-banks, with many stout stems 30-80 cm high, bearing short-stalked somewhat ovate leaves and clusters of purple flowers. It has a stronger flavor and a more penetrating quality. Pot Marjoram or Cretan Oregano (Origanum onites) has similar uses to marjoram. Hardy Marjoram or Italian marjoram is a cross of marjoram with oregano that is much more resistant to cold, but is slightly less sweet. Origanum pulchellum, Showy Marjoram or Showy Oregano. (Catalan marduix; Spanish mejorana) # Surname Marjoram is a surname.	https://www.wikidoc.org/index.php/Marjoram
ceadc5296499c37cd7d3c8c2190b2b6bd70acce9	wikidoc	Mauveine	Mauveine Mauveine, also known as aniline purple and Perkin's mauve, was the first synthetic organic dye. Its chemical name is 3-amino-2,±9-dimethyl-5-phenyl-7-(p-tolylamino)phenazinium acetate. The formula is C26H23N4+X− (mauveine A) and C27H25N4+X− (mauveine B, see below). # History Mauveine was discovered serendipitously in 1856 by an 18-year old, William Henry Perkin, who was trying to synthesize the anti-malaria drug quinine as a challenge offered by his professor, August Wilhelm von Hofmann. In one of his attempts related to the quinine challenge, Perkin oxidized aniline using potassium dichromate. Under these conditions, the aniline reacted with toluidine impurities in it to produce a black solid, a fairly common result in "failed" organic syntheses. However, while trying to clean out his flask, Perkin discovered that some component of the black solid dissolved in alcohol to give a purple-colored solution, which proved to be an effective dye for silk and other textiles. Perkin patented the new dye and the next year, he opened a dyeworks at Greenford on the banks of the Grand Union Canal in London in order to mass produce it. It was originally manufactured under the name of aniline purple or Tyrian purple, also the name of an ancient mollusk-derived natural dye. The name mauve was given to it in England in early 1859, from the French word malva for the mallow flower, and chemists later called it mauveine. Mauve became highly fashionable in 1862 when Queen Victoria of the United Kingdom appeared at the Royal Exhibition in a mauve silk gown. Mauve fell out of fashion in the late 1860s to newer synthetic colors, but not before making Perkin's fortune and birthing the synthetic chemical industry. The U.S. National Association of Confectioners included mauvein among permitted food colorings as of the early 20th century, with a variety of equivalent names: rosolan, violet paste, chrome violet, anilin violet, anilin purple, Perkins violet, indisin, phenamin, purpurin, tyralin, Tyrian purple, and lydin. Later work on chemical dyes also led to the (accidental) development of modern chemotherapy (see Sulfonamide). The color of this dye may be familiar from its widespread use in spirit duplicator (trade name Ditto) printing machines, popular during the mid-20th century. # Chemical analysis A modern-day laboratory procedure for the organic synthesis of mauveine consists of dissolving a mixture of aniline, p-toluidine and o-toluidine in sulfuric acid and water (large excess poor solubility) in roughly a 1:1:2 ratio followed by addition of potassium dichromate . The actual molecular structure of mauveine proved quite difficult to determine and was not known with certainty until 1994. - skeletal formula of mauveine A skeletal formula of mauveine A - skeletal formula of mauveine B skeletal formula of mauveine B - skeletal formula of mauveine B2 skeletal formula of mauveine B2 - skeletal formula of mauveine C skeletal formula of mauveine C It is actually a mixture of four related aromatic compounds, which differ only in the number and placement of methyl groups. A is built up from 2 molecules of aniline, one of p-toluidine and one of o-toluidine whereas B incorporates aniline, p-toluidine and o-toluidine one molecule each. As Perkin showed in 1879, mauveine B is related to the safranines by oxidative/reductive loss of the p-tolyl group. In fact, safranine itself is a 2,8-dimethyl phenazinium salt, whereas the parasafranine produced by Perkin must be presumed to be the 1,8-(or 2,9) dimethyl isomer. In 2007 two other mauveine components were isolated and identified, called mauveine C (an additional p-methyl group on mauveine A) and mauveine B2 (an isomer of mauveine B with methyl on different aryl group).	Mauveine Template:Redirectstohere Mauveine, also known as aniline purple and Perkin's mauve, was the first synthetic organic dye.[1][2] Its chemical name is 3-amino-2,±9-dimethyl-5-phenyl-7-(p-tolylamino)phenazinium acetate. The formula is C26H23N4+X− (mauveine A) and C27H25N4+X− (mauveine B, see below). Template:TOCnestright # History Mauveine was discovered serendipitously in 1856 by an 18-year old, William Henry Perkin, who was trying to synthesize the anti-malaria drug quinine as a challenge offered by his professor, August Wilhelm von Hofmann. In one of his attempts related to the quinine challenge, Perkin oxidized aniline using potassium dichromate. Under these conditions, the aniline reacted with toluidine impurities in it to produce a black solid, a fairly common result in "failed" organic syntheses. However, while trying to clean out his flask, Perkin discovered that some component of the black solid dissolved in alcohol to give a purple-colored solution, which proved to be an effective dye for silk and other textiles. Perkin patented the new dye and the next year, he opened a dyeworks at Greenford on the banks[3] of the Grand Union Canal in London in order to mass produce it. It was originally manufactured under the name of aniline purple or Tyrian purple, also the name of an ancient mollusk-derived natural dye.[4] The name mauve was given to it in England in early 1859, from the French word malva for the mallow flower, and chemists later called it mauveine.[4] Mauve became highly fashionable in 1862 when Queen Victoria of the United Kingdom appeared at the Royal Exhibition in a mauve silk gown. Mauve fell out of fashion in the late 1860s to newer synthetic colors, but not before making Perkin's fortune and birthing the synthetic chemical industry. The U.S. National Association of Confectioners included mauvein among permitted food colorings as of the early 20th century, with a variety of equivalent names: rosolan, violet paste, chrome violet, anilin violet, anilin purple, Perkins violet, indisin, phenamin, purpurin, tyralin, Tyrian purple, and lydin.[5] Later work on chemical dyes also led to the (accidental) development of modern chemotherapy (see Sulfonamide). The color of this dye may be familiar from its widespread use in spirit duplicator (trade name Ditto) printing machines, popular during the mid-20th century. # Chemical analysis A modern-day laboratory procedure for the organic synthesis of mauveine consists of dissolving a mixture of aniline, p-toluidine and o-toluidine in sulfuric acid and water (large excess poor solubility) in roughly a 1:1:2 ratio followed by addition of potassium dichromate [6]. The actual molecular structure of mauveine proved quite difficult to determine and was not known with certainty until 1994.[7] - skeletal formula of mauveine A skeletal formula of mauveine A - skeletal formula of mauveine B skeletal formula of mauveine B - skeletal formula of mauveine B2 skeletal formula of mauveine B2 - skeletal formula of mauveine C skeletal formula of mauveine C It is actually a mixture of four related aromatic compounds, which differ only in the number and placement of methyl groups. A is built up from 2 molecules of aniline, one of p-toluidine and one of o-toluidine whereas B incorporates aniline, p-toluidine and o-toluidine one molecule each. As Perkin showed in 1879,[8] mauveine B is related to the safranines by oxidative/reductive loss of the p-tolyl group. In fact, safranine itself is a 2,8-dimethyl phenazinium salt, whereas the parasafranine produced by Perkin must be presumed[9] to be the 1,8-(or 2,9) dimethyl isomer. In 2007 two other mauveine components were isolated and identified, called mauveine C (an additional p-methyl group on mauveine A) and mauveine B2 (an isomer of mauveine B with methyl on different aryl group). [10] # External links - Perkin anniversary website - Rotatable 3D models of mauveine are available using Jmol	https://www.wikidoc.org/index.php/Mauveine
18eaf5bcd5279c925e1d3df9f65583abcbe36deb	wikidoc	Mazindol	Mazindol # Overview Mazindol is a central nervous system stimulant. It is a tricyclic compound (not to be confused with tricyclic antidepressants). # Indications Mazindol is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m2), or in patients with a body mass index of 27 kg/m2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia. # Pharmacology Mazindol is a sympathomimetic amine, which is similar to amphetamine. It stimulates the central nervous system, which increases heart rate and blood pressure, and decreases appetite. Sympathomimetic anoretics (appetite suppressants) are used in the short-term treatment of obesity. Their appetite-reducing effect tends to decrease after a few weeks of treatment. Because of this, these medicines are useful only during the first few weeks of a weight-loss program. # Mechanism of Action Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Like other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to act as a reuptake inhibitor of norepinephrine. # Overdose Symptoms of a mazindol overdose include: restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.	Mazindol Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Mazindol is a central nervous system stimulant. It is a tricyclic compound (not to be confused with tricyclic antidepressants). # Indications Mazindol is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m2), or in patients with a body mass index of 27 kg/m2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia. # Pharmacology Mazindol is a sympathomimetic amine, which is similar to amphetamine. It stimulates the central nervous system, which increases heart rate and blood pressure, and decreases appetite. Sympathomimetic anoretics (appetite suppressants) are used in the short-term treatment of obesity. Their appetite-reducing effect tends to decrease after a few weeks of treatment. Because of this, these medicines are useful only during the first few weeks of a weight-loss program. # Mechanism of Action Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Like other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to act as a reuptake inhibitor of norepinephrine. # Overdose Symptoms of a mazindol overdose include: restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.	https://www.wikidoc.org/index.php/Mazanor
c186c5736d2118fa765e220d0977de6f9128395f	wikidoc	Mealybug	Mealybug Mealybug is the common name of insects in Pseudococcidae, a family of unarmored scale insects found in moist, warm climates. They are considered pests as they feed on plant juices of greenhouse plants, house plants and subtropical trees. Mealybugs are sexually dimorphic, meaning that the sexes have distinct morphological differences. Females are nymphal, exhibit reduced morphology, and are wingless, though unlike many female scale insects, they often retain legs and can move. The females do not change completely and are likely to be neotenic (exhibiting nymphal characteristics). Males are winged and do change completely during their lives. Since mealybugs (as well as all other Hemiptera) are hemimetabolous insects, they do not undergo complete metamorphosis in the true sense of the word, i.e. there are no clear larval, pupal and adult stages, and the wings do not develop internally. However, male mealybugs do exhibit a radical change during their life cycle, changing from wingless, ovoid nymphs to "wasp-like" flying adults. Mealybug females feed on plant sap, normally in roots or other crevices. They attach themselves to the plant and secrete a powdery wax layer (therefore the name mealybug) used for protection while they suck the plant juices. The males on the other hand, are short-lived as they do not feed at all as adults and only live to fertilize the females. Male citrus mealy bugs fly to the females and resemble fluffy gnats. Some species of mealybug lay their eggs in the same waxy layer used for protection in quantities of 50–100; other species are born directly from the female. The most serious pests are mealybugs that feed on citrus; other species damage sugarcane, grapes, pineapple (Jahn et al. 2003), coffee trees, cassava, ferns, cacti and orchids. Mealybugs only tend to be serious pests in the presences of ants because the ants protect them from predators and parasites. Mealybugs also infest some species of carnivorous plant such as Sarracenia (pitcher plants), in such cases it is difficult to eradicate them without repeated applications of insecticide such as diazinon. Small infestations may not inflict significant damage. In larger amounts though, they can induce leaf drop. # Species include - Maconellicoccus hirsutus - pink hibiscus mealybug, grape mealybug - Planococcus citri - citrus mealybug - Pseudococcus viburni - obscure mealybug	Mealybug Template:Wikispecies Mealybug is the common name of insects in Pseudococcidae, a family of unarmored scale insects found in moist, warm climates. They are considered pests as they feed on plant juices of greenhouse plants, house plants and subtropical trees. Mealybugs are sexually dimorphic, meaning that the sexes have distinct morphological differences. Females are nymphal, exhibit reduced morphology, and are wingless, though unlike many female scale insects, they often retain legs and can move. The females do not change completely and are likely to be neotenic (exhibiting nymphal characteristics). Males are winged and do change completely during their lives. Since mealybugs (as well as all other Hemiptera) are hemimetabolous insects, they do not undergo complete metamorphosis in the true sense of the word, i.e. there are no clear larval, pupal and adult stages, and the wings do not develop internally. However, male mealybugs do exhibit a radical change during their life cycle, changing from wingless, ovoid nymphs to "wasp-like" flying adults. Mealybug females feed on plant sap, normally in roots or other crevices. They attach themselves to the plant and secrete a powdery wax layer (therefore the name mealybug) used for protection while they suck the plant juices. The males on the other hand, are short-lived as they do not feed at all as adults and only live to fertilize the females. Male citrus mealy bugs fly to the females and resemble fluffy gnats. Some species of mealybug lay their eggs in the same waxy layer used for protection in quantities of 50–100; other species are born directly from the female. The most serious pests are mealybugs that feed on citrus; other species damage sugarcane, grapes, pineapple (Jahn et al. 2003), coffee trees, cassava, ferns, cacti and orchids. Mealybugs only tend to be serious pests in the presences of ants because the ants protect them from predators and parasites. Mealybugs also infest some species of carnivorous plant such as Sarracenia (pitcher plants), in such cases it is difficult to eradicate them without repeated applications of insecticide such as diazinon. Small infestations may not inflict significant damage. In larger amounts though, they can induce leaf drop. ## Species include - Maconellicoccus hirsutus - pink hibiscus mealybug, grape mealybug - Planococcus citri - citrus mealybug - Pseudococcus viburni - obscure mealybug	https://www.wikidoc.org/index.php/Mealybug
a9cb78ac4afb6607df231a5a5b7369218a7a7c6c	wikidoc	Meconium	Meconium # Overview Meconium is the first stool of an infant, composed of materials ingested during the time the infant spends in the uterus: Intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium is sterile, unlike later feces, is viscous and sticky like tar, and has no odor. It should be completely passed by the end of the first few days of postpartum life, with the stools progressing toward yellow (digested milk). The term Meconium derives from meconium-arion, meaning "opium-like", in reference either to its tarry appearance or Aristotle's belief that it induced sleep in the fetus. Meconium is normally stored in the infant's intestines until after birth, but sometimes it is expelled into the amniotic fluid prior to birth or during labor and delivery. Sometimes the meconium becomes thickened and congested in the ileum, a condition known as meconium ileus. Meconium ileus is often the first symptom of cystic fibrosis. Meconium can be tested for various drugs, to check for in utero exposure. The results of meconium testing run on a newborn can be turned in to child protective services and other law enforcement agencies. Meconium is also used to describe the metabolic waste product from the pupal stage that is expelled through the anal opening of the adult butterfly upon eclosion from the chrysalis.	Meconium # Overview Meconium is the first stool of an infant, composed of materials ingested during the time the infant spends in the uterus: Intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium is sterile, unlike later feces, is viscous and sticky like tar, and has no odor. It should be completely passed by the end of the first few days of postpartum life, with the stools progressing toward yellow (digested milk). The term Meconium derives from meconium-arion, meaning "opium-like", in reference either to its tarry appearance or Aristotle's belief that it induced sleep in the fetus.[1] Meconium is normally stored in the infant's intestines until after birth, but sometimes it is expelled into the amniotic fluid prior to birth or during labor and delivery. Sometimes the meconium becomes thickened and congested in the ileum, a condition known as meconium ileus. Meconium ileus is often the first symptom of cystic fibrosis. Meconium can be tested for various drugs, to check for in utero exposure. The results of meconium testing run on a newborn can be turned in to child protective services and other law enforcement agencies.[2] Meconium is also used to describe the metabolic waste product from the pupal stage that is expelled through the anal opening of the adult butterfly upon eclosion from the chrysalis.	https://www.wikidoc.org/index.php/Meconium
6317ebb728b937813aec1a763ddaf7ef0fbfeb40	wikidoc	Mediator	Mediator Mediator may refer to: - A neutral party who assists in negotiations and conflict resolution, the process being known as mediation - By analogy, someone who channels contact between mortals and divinity; e.g. in the Christian faith, Christ is sometimes referred to as the mediator between humanity and God the Father (external link: ) - Médiateur de la Confédération Helvétique was Napoleon I Bonaparte's title as hegemon in French-occupied Switzerland; - Mediator variable in statistics; - Mediator design pattern in computer science; - MatchWare Mediator, an advanced multimedia authoring tool for Windows; - The multiprotein Mediator complex in Molecular Biology functions as a transcriptional coactivator; - Mediator is a series of six books written by Meg Cabot originally under the pseudonym of Jenny Carol; - Names used for Jesus de:Mediator et:Mediaator lt:Mediatorius nl:Mediator	Mediator Mediator may refer to: - A neutral party who assists in negotiations and conflict resolution, the process being known as mediation - By analogy, someone who channels contact between mortals and divinity; e.g. in the Christian faith, Christ is sometimes referred to as the mediator between humanity and God the Father (external link: [1]) - Médiateur de la Confédération Helvétique was Napoleon I Bonaparte's title as hegemon in French-occupied Switzerland; - Mediator variable in statistics; - Mediator design pattern in computer science; - MatchWare Mediator, an advanced multimedia authoring tool for Windows; - The multiprotein Mediator complex in Molecular Biology functions as a transcriptional coactivator; - Mediator is a series of six books written by Meg Cabot originally under the pseudonym of Jenny Carol; - Names used for Jesus Template:Disambig de:Mediator et:Mediaator lt:Mediatorius nl:Mediator Template:WS	https://www.wikidoc.org/index.php/Mediator
5a8b0338dd342cd376f28da0971daa375ba1b7f4	wikidoc	Oncology	Oncology # Overview Oncology is the branch of medicine that studies tumors (cancer) and seeks to understand their development, diagnosis, treatment, and prevention. A Medical professional who practices oncology is an oncologist. The term originates from the Greek ogkos (ογκος), meaning bulk, mass, or tumor and the suffix -ology, meaning "study of". The oncologist often coordinates the multidisciplinary care of cancer patients, which may involve physiotherapy, counselling, clinical genetics, to name but a few. On the other hand, the oncologist often has to liaise with pathologists on the exact biological nature of the tumor that is being treated. Oncology is concerned with: - The diagnosis of cancer - Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) - Follow-up of cancer patients after successful treatment - Palliative care of patients with terminal malignancies - Ethical questions surrounding cancer care - Screening efforts: -f populations, or -f the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer). - of populations, or - of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer). # Diagnosis The most important diagnostic tool remains the medical history: the character of the complaints and any specific symptoms (fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplastic phenomena and other signs). Often a physical examination will reveal the location of a malignancy. Diagnostic methods include: - Biopsy, either incisional or excisional; - Endoscopy, either upper or lower gastrointestinal, bronchoscopy, or nasendoscopy; - X-rays, CT scanning, MRI scanning, ultrasound and other radiological techniques; - Scintigraphy, Positron emission tomography and other methods of nuclear medicine; - Blood tests, including Tumor markers, which can increase the suspicion of certain types of tumors or even be pathognomonic of a particular disease. Apart from in diagnosis, these modalities (especially imaging by CT scanning) are often used to determine operability, i.e. whether it is surgically possible to remove a tumor in its entirety. Generally, a "tissue diagnosis" (from a biopsy) is considered essential for the proper identification of cancer. When this is not possible, empirical therapy (without an exact diagnosis) may be given, based on the available evidence (e.g. history, x-rays and scans.) Occasionally, a metastatic lump or pathological lymph node is found (typically in the neck) for which a primary tumor cannot be found. This situation is referred to as " carcinoma of unknown primary", and again, treatment is empirical based on past experience of the most likely origin. # Therapy It depends completely on the nature of the tumor identified what kind of therapeutical intervention will be necessary. Certain disorders will require immediate admission and chemotherapy (such as ALL or AML), while others will be followed up with regular physical examination and blood tests. Often, surgery is attempted to remove a tumor entirely. This is only feasible when there is some degree of certainty that the tumor can in fact be removed. When it is certain that parts will remain, curative surgery is often impossible, e.g. when there are metastases elsewhere, or when the tumor has invaded a structure that cannot be operated upon without risking the patient's life. Occasionally surgery can improve survival even if not all tumour tissue has been removed; the procedure is referred to as "debulking" (i.e. reducing the overall amount of tumour tissue). Surgery is also used for the palliative treatment of some of cancers, e.g. to relieve biliary obstruction, or to relieve the problems associated with some cerebral tumours. The risks of surgery must be weighed up against the benefits. Chemotherapy and radiotherapy are used as a first-line radical therapy in a number of malignancies. They are also used for adjuvant therapy, i.e. when the macroscopic tumor has already been completely removed surgically but there is a reasonable statistical risk that it will recur. Chemotherapy and radiotherapy are commonly used for palliation, where disease is clearly incurable: in this situation the aim is to improve the quality of and prolong life. Hormone manipulation is well established, particularly in the treatment of breast and prostate cancer. There is currently a rapid expansion in the use of monoclonal antibody treatments, notably for lymphoma (Rituximab), and breast cancer (Trastuzumab). Vaccine and other immunotherapies are the subject of intensive research. The application of ultrasound in the form of HIFU to solid tumors is under investigation. # Follow-up A large segment of the oncologist's workload is the following-up of cancer patients who have been successfully treated. For some cancers, early identification of recurrence, with prompt treatment, can lead to better survival and quality of life. It depends on the nature of the cancer whether the follow-up lasts a number of years or remains "life long". # Palliative care Approximately 50% of all cancer cases in the Western world can be cured with radical treatment. For pediatric patients, that number is much higher. A large number of cancer patients will die from the disease, and a significant proportion of patients with incurable cancer will die of other causes. There may be ongoing issues with symptom control associated with progressive cancer, and also with the treatment of the disease. These problems may include pain, nausea, anorexia, fatigue, immobility, and depression. Not all issues are strictly physical: personal dignity may be affected. Moral and spiritual issues are also important. While many of these problems fall within the remit of the oncologist, palliative care has matured into a separate, closely allied speciality to address the problems associated with advanced disease. Palliative care is an essential part of the multidisciplinary cancer care team. Palliative care services may be less hospital-based than oncology, with nurses and doctors who are able to visit the patient at home. # Ethical issues There are a number of recurring ethical questions and dilemmas in oncological practice. These include: - What information to give the patient regarding disease extent/progression/prognosis. - Entry into clinical trials, especially in the face of terminal illness. - Withdrawal of active treatment. - "Do Not Resuscitate" orders and other end of life issues. These issues are closely related to the patients' personality, religion, culture, personal, and family life. The answers are rarely black and white. It requires a degree of sensitivity and very good communication on the part of the oncology team to address these problems properly. # Progress and research in oncology There is a tremendous amount of research being conducted on all frontiers of oncology, ranging from cancer cell biology to chemotherapy treatment regimens and optimal palliative care and pain relief. This makes oncology an exciting and continuously changing field. Therapeutic trials often involve patients from many different hospitals in a particular region. In the UK, patients are often enrolled in large studies coordinated by Cancer Research UK (CRUK, ), Medical Research Council (MRC, ), the European Organisation for Research and Treatment of Cancer (EORTC, ) or the National Cancer Research Network (NCRN, ). # Complementary and alternative therapies Many cancer patients seek extra help from complementary and alternative therapies, which fall outside of conventional medicine. Most complementary therapies do not have a firm scientific or evidence base. Some patients undoubtedly find complementary therapies helpful while they are undergoing conventional treatment. While most complementary therapies are probably harmless, they can be expensive. They may also be positively harmful if the patient forgoes conventional treatment altogether, in order to follow alternative regimens. Some alternative regimens are undoubtedly hazardous. # Specialities There are several subspecialties within oncology. Moreover, oncologists often develop an interest and expertise in the management of particular types of cancer. Oncologists may be divided on the basis of the type of treatment provided. - Radiation oncology: treatment primarily with radiation, a process called radiotherapy. - Surgical oncology: surgeons who specialize in tumor removal. - In the United Kingdom and several other countries, oncologists may be either clinical or medical oncologists. The main difference is that clinical oncologists deliver radiotherapy, while medical oncologists do not. Gynecologic oncology focuses on cancers of the female reproductive system. In veterinary medicine, veterinary oncology is the subspecialty that deals with cancer diagnosis and treatment in animals.	Oncology Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Oncology is the branch of medicine that studies tumors (cancer) and seeks to understand their development, diagnosis, treatment, and prevention. A Medical professional who practices oncology is an oncologist. The term originates from the Greek ogkos (ογκος), meaning bulk, mass, or tumor and the suffix -ology, meaning "study of". The oncologist often coordinates the multidisciplinary care of cancer patients, which may involve physiotherapy, counselling, clinical genetics, to name but a few. On the other hand, the oncologist often has to liaise with pathologists on the exact biological nature of the tumor that is being treated. Oncology is concerned with: - The diagnosis of cancer - Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) - Follow-up of cancer patients after successful treatment - Palliative care of patients with terminal malignancies - Ethical questions surrounding cancer care - Screening efforts: of populations, or of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer). - of populations, or - of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer). # Diagnosis The most important diagnostic tool remains the medical history: the character of the complaints and any specific symptoms (fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplastic phenomena and other signs). Often a physical examination will reveal the location of a malignancy. Diagnostic methods include: - Biopsy, either incisional or excisional; - Endoscopy, either upper or lower gastrointestinal, bronchoscopy, or nasendoscopy; - X-rays, CT scanning, MRI scanning, ultrasound and other radiological techniques; - Scintigraphy, Positron emission tomography and other methods of nuclear medicine; - Blood tests, including Tumor markers, which can increase the suspicion of certain types of tumors or even be pathognomonic of a particular disease. Apart from in diagnosis, these modalities (especially imaging by CT scanning) are often used to determine operability, i.e. whether it is surgically possible to remove a tumor in its entirety. Generally, a "tissue diagnosis" (from a biopsy) is considered essential for the proper identification of cancer. When this is not possible, empirical therapy (without an exact diagnosis) may be given, based on the available evidence (e.g. history, x-rays and scans.) Occasionally, a metastatic lump or pathological lymph node is found (typically in the neck) for which a primary tumor cannot be found. This situation is referred to as " carcinoma of unknown primary", and again, treatment is empirical based on past experience of the most likely origin. # Therapy It depends completely on the nature of the tumor identified what kind of therapeutical intervention will be necessary. Certain disorders will require immediate admission and chemotherapy (such as ALL or AML), while others will be followed up with regular physical examination and blood tests. Often, surgery is attempted to remove a tumor entirely. This is only feasible when there is some degree of certainty that the tumor can in fact be removed. When it is certain that parts will remain, curative surgery is often impossible, e.g. when there are metastases elsewhere, or when the tumor has invaded a structure that cannot be operated upon without risking the patient's life. Occasionally surgery can improve survival even if not all tumour tissue has been removed; the procedure is referred to as "debulking" (i.e. reducing the overall amount of tumour tissue). Surgery is also used for the palliative treatment of some of cancers, e.g. to relieve biliary obstruction, or to relieve the problems associated with some cerebral tumours. The risks of surgery must be weighed up against the benefits. Chemotherapy and radiotherapy are used as a first-line radical therapy in a number of malignancies. They are also used for adjuvant therapy, i.e. when the macroscopic tumor has already been completely removed surgically but there is a reasonable statistical risk that it will recur. Chemotherapy and radiotherapy are commonly used for palliation, where disease is clearly incurable: in this situation the aim is to improve the quality of and prolong life. Hormone manipulation is well established, particularly in the treatment of breast and prostate cancer. There is currently a rapid expansion in the use of monoclonal antibody treatments, notably for lymphoma (Rituximab), and breast cancer (Trastuzumab). Vaccine and other immunotherapies are the subject of intensive research. The application of ultrasound in the form of HIFU to solid tumors is under investigation. # Follow-up A large segment of the oncologist's workload is the following-up of cancer patients who have been successfully treated. For some cancers, early identification of recurrence, with prompt treatment, can lead to better survival and quality of life. It depends on the nature of the cancer whether the follow-up lasts a number of years or remains "life long". # Palliative care Approximately 50% of all cancer cases in the Western world can be cured with radical treatment. For pediatric patients, that number is much higher. A large number of cancer patients will die from the disease, and a significant proportion of patients with incurable cancer will die of other causes. There may be ongoing issues with symptom control associated with progressive cancer, and also with the treatment of the disease. These problems may include pain, nausea, anorexia, fatigue, immobility, and depression. Not all issues are strictly physical: personal dignity may be affected. Moral and spiritual issues are also important. While many of these problems fall within the remit of the oncologist, palliative care has matured into a separate, closely allied speciality to address the problems associated with advanced disease. Palliative care is an essential part of the multidisciplinary cancer care team. Palliative care services may be less hospital-based than oncology, with nurses and doctors who are able to visit the patient at home. # Ethical issues There are a number of recurring ethical questions and dilemmas in oncological practice. These include: - What information to give the patient regarding disease extent/progression/prognosis. - Entry into clinical trials, especially in the face of terminal illness. - Withdrawal of active treatment. - "Do Not Resuscitate" orders and other end of life issues. These issues are closely related to the patients' personality, religion, culture, personal, and family life. The answers are rarely black and white. It requires a degree of sensitivity and very good communication on the part of the oncology team to address these problems properly. # Progress and research in oncology There is a tremendous amount of research being conducted on all frontiers of oncology, ranging from cancer cell biology to chemotherapy treatment regimens and optimal palliative care and pain relief. This makes oncology an exciting and continuously changing field. Therapeutic trials often involve patients from many different hospitals in a particular region. In the UK, patients are often enrolled in large studies coordinated by Cancer Research UK (CRUK, [2]), Medical Research Council (MRC, [3]), the European Organisation for Research and Treatment of Cancer (EORTC, [4]) or the National Cancer Research Network (NCRN, [5]). # Complementary and alternative therapies Many cancer patients seek extra help from complementary and alternative therapies, which fall outside of conventional medicine. Most complementary therapies do not have a firm scientific or evidence base. Some patients undoubtedly find complementary therapies helpful while they are undergoing conventional treatment. While most complementary therapies are probably harmless, they can be expensive. They may also be positively harmful if the patient forgoes conventional treatment altogether, in order to follow alternative regimens. Some alternative regimens are undoubtedly hazardous. # Specialities There are several subspecialties within oncology. Moreover, oncologists often develop an interest and expertise in the management of particular types of cancer. Oncologists may be divided on the basis of the type of treatment provided. - Radiation oncology: treatment primarily with radiation, a process called radiotherapy. - Surgical oncology: surgeons who specialize in tumor removal. - In the United Kingdom and several other countries, oncologists may be either clinical or medical oncologists. The main difference is that clinical oncologists deliver radiotherapy, while medical oncologists do not. Gynecologic oncology focuses on cancers of the female reproductive system. In veterinary medicine, veterinary oncology is the subspecialty that deals with cancer diagnosis and treatment in animals.	https://www.wikidoc.org/index.php/Medical_oncology
3081a6456a14d78769224a0923afca23367e167b	wikidoc	Melanism	Melanism Melanism is an increased amount of black or nearly black pigmentation (as of skin, feathers, or hair) of an organism, resulting from the presence of melanin. It is the opposite of albinism, which occurs due to lack of melanin. More technically, it refers to a phenotype in which the pigmentation of an organism is entirely, or nearly entirely, expressed. A synonym for this condition used in the context of human disease is melanosis. Abundism is an increase in dark pigmentation in patterned coats or skins which causes an increase in the number or size of pigmented spots, stripes or other patch types. Abundism which is sufficiently extreme to appear like melanism, such as when the stripes of a striped animal increase in width sufficiently to overlap, is known as pseudo-melanism. Melanism and abundism are often the result of genetic mutation, but can result from other stimuli, such as exposure to abnormal temperature changes during gestation which transiently alter gene transcription or translation. Melanism or abundism triggered by human modification of the environment is known as industrial melanism; the history of this phenomenon in the peppered moth in the United Kingdom is a classic instructional tool for teaching the principles of natural selection. Melanism has been shown to occur in a variety of animals, including mammals (squirrels, many felines, many canids); reptiles (coral snakes); and insects (peppered moth). Many examples of melanism are known among felines. Melanism is due to changes in the agouti gene which controls banding of black and light areas on the hair shaft. Leopards and jaguars with this condition are often called black panther (although cougars are also known as panthers, there are no verified cases of melanism in that species). However, the leopard, the jaguar, the lion and the tiger are all members of the Panthera genus. One good example of melanism expressed within a certain animal community is that of the leopard population in Malaysia, South East Asia, in which case up to 50% of the population has melanism. That is apparently due to them being more cryptic in their dusky rainforest habitat. Better resistance to viruses may also explain the greater prevalence of black leopards in those areas. In the Jaguar, melanism is due to a dominant gene mutation meaning that black jaguars may produce spotted offspring. In the leopard, melanism is due to a recessive gene mutation meaning that two spotted leopards carrying the gene may produce black cubs, but black leopards will breed true when mated together. # Industrial melanism Melanism is a phenomenon caused by anthropogenic alteration of the natural environment where industrial pollution turns vegetation a dark sooty colour. Because many organisms rely on camouflage to avoid predation, the sudden change in environment makes them highly vulnerable to predators. This creates a strong selective pressure which will see any organism with a darker colour much more likely to survive and contribute to the gene pool of the next generation. Rare mutations are hence selected for and over time the population will adjust to a new equilibrium. # Melanism and the immune system Melanism has been found to be linked to beneficial changes in the immune system. "The Smithsonian Answer Book: Cats" notes that genes for melanism in felids may provide resistance from viral infections and that a viral epidemic may explain the prevalence of black leopards in Java and Malaysia, and the relatively high incidence of black leopards and black servals in the Aberdares region of Africa. Previously, black furred felids in the Aberdares had been considered a high altitude adaptation due to absorbing more heat. Studies reported in New Scientist magazine in 2003 also suggested that recessive-gene melanism is linked to disease resistance rather than altitude. According to Eduardo Eizirik and Stephen O'Brien of the United States National Cancer Institute in Maryland, the melanism mutations involve the same gene family as those involved in human diseases such as AIDS. Melanistic cats may therefore have better resistance to disease than cats with "normal" colour coats. This would explain why recessive melanism persists when melanistic individuals are disadvantaged due to being poorly camouflaged in open areas. In the United States National Cancer Institute studies, black cats were found to have changes to a gene known as MC1R. MC1R is a member of a family of genes that includes the human gene CCR5 which codes for a protein on the cell membrane. This protein is a key allowing in various viruses, including HIV. Melanism could make black cats less susceptible to certain viral infections making melanism an evolutionary advantage. # Pseudo-melanism and abundism In animal species that normally have black markings on a paler background colour, excessively abundant markings (abundism) which merge or overlap produce an effect called pseudo-melanism. The background colour may still be discerned between the markings, but to the casual observer, or from a distance, the animals appears to be black.. # Melanism as a socio-political movement The term melanism has been used on usenet, internet forums and blogs to mean an African-American social movement holding that dark-skinned humans are in some measures superior to those of other skin colour. The term melanism has been used in this context as early as the mid-1990s and was promoted by some Afrocentrists, such as Frances Cress Welsing. # Further reading - Template:Cite visual - Kettlewell, Bernard (1973). The Evolution of Melanism. Clarendon Press. ISBN 0-19-857370-7..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} - Majerus, Michael (1998). Melanism: Evolution in Action. Oxford University Press. ISBN 0-19-854982-2. - Melanism and disease resistance in insects	Melanism Melanism is an increased amount of black or nearly black pigmentation (as of skin, feathers, or hair) of an organism, resulting from the presence of melanin. It is the opposite of albinism, which occurs due to lack of melanin. More technically, it refers to a phenotype in which the pigmentation of an organism is entirely, or nearly entirely, expressed. A synonym for this condition used in the context of human disease is melanosis. Abundism is an increase in dark pigmentation in patterned coats or skins which causes an increase in the number or size of pigmented spots, stripes or other patch types. Abundism which is sufficiently extreme to appear like melanism, such as when the stripes of a striped animal increase in width sufficiently to overlap, is known as pseudo-melanism. Melanism and abundism are often the result of genetic mutation, but can result from other stimuli, such as exposure to abnormal temperature changes during gestation which transiently alter gene transcription or translation. Melanism or abundism triggered by human modification of the environment is known as industrial melanism; the history of this phenomenon in the peppered moth in the United Kingdom is a classic instructional tool for teaching the principles of natural selection. Melanism has been shown to occur in a variety of animals, including mammals (squirrels, many felines, many canids); reptiles (coral snakes); and insects (peppered moth). Many examples of melanism are known among felines. Melanism is due to changes in the agouti gene which controls banding of black and light areas on the hair shaft. Leopards and jaguars with this condition are often called black panther (although cougars are also known as panthers, there are no verified cases of melanism in that species). However, the leopard, the jaguar, the lion and the tiger are all members of the Panthera genus. One good example of melanism expressed within a certain animal community is that of the leopard population in Malaysia, South East Asia, in which case up to 50% of the population has melanism. That is apparently due to them being more cryptic in their dusky rainforest habitat. Better resistance to viruses may also explain the greater prevalence of black leopards in those areas. In the Jaguar, melanism is due to a dominant gene mutation meaning that black jaguars may produce spotted offspring. In the leopard, melanism is due to a recessive gene mutation meaning that two spotted leopards carrying the gene may produce black cubs, but black leopards will breed true when mated together. # Industrial melanism Melanism is a phenomenon caused by anthropogenic alteration of the natural environment where industrial pollution turns vegetation a dark sooty colour. Because many organisms rely on camouflage to avoid predation, the sudden change in environment makes them highly vulnerable to predators. This creates a strong selective pressure which will see any organism with a darker colour much more likely to survive and contribute to the gene pool of the next generation. Rare mutations are hence selected for and over time the population will adjust to a new equilibrium. # Melanism and the immune system Melanism has been found to be linked to beneficial changes in the immune system. "The Smithsonian Answer Book: Cats" notes that genes for melanism in felids may provide resistance from viral infections and that a viral epidemic may explain the prevalence of black leopards in Java and Malaysia, and the relatively high incidence of black leopards and black servals in the Aberdares region of Africa.[citation needed] Previously, black furred felids in the Aberdares had been considered a high altitude adaptation due to absorbing more heat.[citation needed] Studies reported in New Scientist magazine in 2003 also suggested that recessive-gene melanism is linked to disease resistance rather than altitude.[citation needed] According to Eduardo Eizirik and Stephen O'Brien of the United States National Cancer Institute in Maryland, the melanism mutations involve the same gene family as those involved in human diseases such as AIDS.[citation needed] Melanistic cats may therefore have better resistance to disease than cats with "normal" colour coats. This would explain why recessive melanism persists when melanistic individuals are disadvantaged due to being poorly camouflaged in open areas. In the United States National Cancer Institute studies, black cats were found to have changes to a gene known as MC1R.[citation needed] MC1R is a member of a family of genes that includes the human gene CCR5 which codes for a protein on the cell membrane. This protein is a key allowing in various viruses, including HIV. Melanism could make black cats less susceptible to certain viral infections making melanism an evolutionary advantage. # Pseudo-melanism and abundism In animal species that normally have black markings on a paler background colour, excessively abundant markings (abundism) which merge or overlap produce an effect called pseudo-melanism. The background colour may still be discerned between the markings, but to the casual observer, or from a distance, the animals appears to be black.. # Melanism as a socio-political movement The term melanism has been used on usenet, internet forums and blogs to mean an African-American social movement holding that dark-skinned humans are in some measures superior to those of other skin colour. The term melanism has been used in this context as early as the mid-1990s[2] and was promoted by some Afrocentrists, such as Frances Cress Welsing. # Further reading - Template:Cite visual - Kettlewell, Bernard (1973). The Evolution of Melanism. Clarendon Press. ISBN 0-19-857370-7..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} - Majerus, Michael (1998). Melanism: Evolution in Action. Oxford University Press. ISBN 0-19-854982-2. - Melanism and disease resistance in insects	https://www.wikidoc.org/index.php/Melanism
95a275d3dcd622261e4051439f9ae79463586709	wikidoc	Memetics	Memetics Memetics is a neo-Darwinian approach to evolutionary models of cultural information transfer based on the concept of the meme. Started from a metaphor used in popular writings of Richard Dawkins, it has later turned into an approach in the study of self-replicating units of culture. It has been proposed that just as memes are analogous to genes, memetics is analogous to genetics. # History of the term In his book The Selfish Gene (1976), the ethologist Richard Dawkins used the term meme to describe a unit of human cultural transmission analogous to the gene, arguing that replication also happens in culture, albeit in a different sense. In his book, Dawkins contended that the meme is a unit of information residing in the brain and is the mutating replicator in human cultural evolution. It is a pattern that can influence its surroundings – that is, it has causal agency – and can propagate. This created great debate among sociologists, biologists, and scientists of other disciplines, because Dawkins himself did not provide a sufficient explanation of how the replication of units of information in the brain controls human behaviour and ultimately culture, since the principal topic of the book was genetics. Dawkins apparently did not intend to present a comprehensive theory of memetics in The Selfish Gene, but rather coined the term meme in a speculative spirit. Accordingly, the term "unit of information" came to be defined in different ways by many scientists. The modern memetics movement dates from the mid 1980s. A January 1983 Metamagical Themas column by Douglas Hofstadter in Scientific American was influential as was his 1985 book of the same name. "Arel Lucas suggested that the discipline that studies memes and their connections to human and other carriers of them be known as memetics by analogy with 'genetics.'" (This might not be the earliest use of "memetics.") The massive popular impact of Dawkins' The Selfish Gene has undoubtedly been an important factor in drawing in people of disparate intellectual backgrounds. Another crucial stimulus was the publication in 1992 of Consciousness Explained by Tufts University philosopher Daniel Dennett, which incorporated the meme concept into an influential theory of the mind. In his 1993 essay Viruses of the Mind, Richard Dawkins used memetics to explain the phenomenon of religious belief and the various characteristics of organised religions. However, the foundation of memetics in full modern incarnation originates in the publication in 1996, of two books by authors outside the academic mainstream: Virus of the Mind: The New Science of the Meme by former Microsoft executive turned motivational speaker and professional poker player, Richard Brodie, and Thought Contagion: How Belief Spreads Through Society by Aaron Lynch, a mathematician and philosopher who worked for many years as an engineer at Fermilab. Lynch claimed to have conceived his theory totally independently of any contact with academics in the cultural evolutionary sphere, and apparently was not even aware of Dawkins' The Selfish Gene until his book was very close to publication. Around the same time as the publication of the books by Lynch and Brodie, a new e-journal appeared on the web, hosted by the Centre for Policy Modelling at Manchester Metropolitan University Journal of Memetics – Evolutionary Models of Information Transmission. The journal has since then been taken over by Francis Heylighen of the CLEA research institute at the Vrije Universiteit Brussel. The e-journal soon became the central point for publication and debate within the nascent memetics community. (There had been a short-lived paper memetics publication starting in 1990, the Journal of Ideas edited by Elan Moritz. )) In 1999, Susan Blackmore, a psychologist at the University of the West of England, published The Meme Machine, which more fully worked out the ideas of Dennett, Lynch and Brodie and attempted to compare and contrast them with various approaches from the cultural evolutionary mainstream, as well as providing novel, and controversial, memetic-based theories for the evolution of language and the human sense of individual selfhood. The term is a transliteration of the Ancient Greek Template:Unicode (Template:Unicode), meaning "imitator, pretender", and was used in 1904 by the German evolutionary biologist Richard Semon, best known for his development of the engram theory of memory, in his work Die mnemischen Empfindungen in ihren Beziehungen zu den Originalempfindungen, translated into English in 1921 as The Mneme. Until Daniel Schacter published Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory in 2000, Semon's work had little influence. # Internalists and externalists The memetics movement split almost immediately into those who want to stick to Dawkins' definition of a meme as "a unit of cultural transmission." Typical of this first group is Gibran Burchett, the founder of Aether Lumin Research firm, who has stated that a meme can be defined, more precisely, as a unit of cultural information ... located in the brain." A second group wants to redefine memes as observable cultural artifacts and behaviours. These two schools became known as the "internalists" and the "externalists." Prominent internalists included both Lynch and Brodie; the most vocal externalists included Derek Gatherer, a geneticist from Liverpool John Moores University and William Benzon, a writer on cultural evolution and music. The main rationale for externalism was that internal brain entities are not observable, and memetics cannot advance as a science, especially a quantitative science, unless it moves its emphasis onto the directly quantifiable aspects of culture. Internalists countered with various arguments: that brain states will eventually be directly observable with advanced technology, that most cultural anthropologists agree that culture is about beliefs and not artefacts, or that artefacts cannot be replicators in the same sense as mental entities (or DNA) are replicators. The debate became so heated that a 1998 Symposium on Memetics, organised as part of the 15th International Conference on Cybernetics, passed a motion calling for an end to definitional debates. The most advanced statement of the internalist school came in 2002 with the publication of The Electric Meme, by Robert Aunger, an anthropologist from the University of Cambridge. Aunger also organised a conference in Cambridge in 1999, at which prominent sociologists and anthropologists were able to give their assessment of the progress made in memetics to that date. This resulted in the publication of Darwinizing Culture: The Status of Memetics as a Science, edited by Aunger and with a foreword by Dennett, in 2000. # Maturity In 2005, the Journal of Memetics – Evolutionary Models of Information Transmission ceased publication and published a set of "obituaries" for memetics. This was not intended to suggest that there can be no further work on memetics. A relaunch of this journal is in the works and the journal is again accepting new submissions . Susan Blackmore has left the University of the West of England to become a freelance science writer and now concentrates more on the field of consciousness and cognitive science. Derek Gatherer moved to work as a computer programmer in the pharmaceutical industry, although he still occasionally publishes on memetics-related matters. Richard Brodie is now climbing the world professional poker rankings. Aaron Lynch disowned the memetics community and the words "meme" and "memetics" (without disowning the ideas in his book), adopting the self-description "thought contagionist". Lynch lost his previous funding from a private sponsor and after his book royalties declined, he was unable to support himself as a private memetics/thought-contagion consultant. He died in 2005. Susan Blackmore (2002) re-stated the meme definition as whatever is copied from one person to another person, whether habits, skills, songs, stories, or any other kind of information. Further she said that memes, like genes, are replicators. That is, they are information that is copied with variation and selection. Because only some of the variants survive, memes (and hence human cultures) evolve. Memes are copied by imitation, teaching and other methods, and they compete for space in our memories and for the chance to be copied again. Large groups of memes that are copied and passed on together are called co-adapted meme complexes, or memeplexes. In her definition, thus, the way that a meme replicates is through imitation. This requires brain capacity to generally imitate a model or selectively imitate the model. Since the process of social learning varies from one person to another, the imitation process cannot be said to be completely imitated. The sameness of an idea may be expressed with different memes supporting it. This is to say that the mutation rate in memetic evolution is extremely high, and mutations are even possible within each and every interaction of the imitation process. It becomes very interesting when we see that a social system composed of a complex network of microinteractions exists, but at the macro level an order emerges to create culture. # Critique Benitez-Bribiesca, a critic to memetics, calls it "a pseudoscientific dogma" and "a dangerous idea that poses a threat to the serious study of conciousness and cultural evolution" among other things. As factual criticism, he refers to the lack of a code script for memes, as the DNA is for genes, and to the fact that the meme mutation mechanism (i.e., an idea going from one brain to another) is too unstable (low replication accuracy and high mutation rate), which would render the evolutionary process chaotic. Another scientific critique comes from semiotics, (e.g., Deacon, Kull) stating that the concept of meme is a primitivized concept of sign. Meme is thus described in memetics as a sign without its triadic nature. In other words, meme is a degenerate sign, which includes only its ability of being copied. Accordingly, the objects of copying are memes, whereas the objects of translation (sensu lato) and interpretation are signs. # New developments Dawkins responds in A Devil's Chaplain that there are actually two different types of memetic processes. The first is a type of cultural idea, action, or expression, which does have high variance; for instance, a student of his who had inherited some of the mannerisms of Wittgenstein. However, he also describes a self-correcting meme, highly resistant to mutation. As an example of this, he gives origami patterns in elementary schools – except in rare cases, the meme is either passed on in the exact sequence of instructions, or (in the case of a forgetful child) terminates. This type of meme tends not to evolve, and to experience profound mutations in the rare event that it does. Some memeticists, however, see this as more of a continuum of meme strength, rather than two types of memes. Another definition, given by Hokky Situngkir, tried to offer a more rigorous formalism for the meme, memeplexes, and the deme, seeing the meme as a cultural unit in a cultural complex system. It is based on the Darwinian genetic algorithm with some modifications to account for the different patterns of evolution seen in genes and memes. In the method of memetics as the way to see culture as a complex adaptive system, he describes a way to see memetics as an alternative methodology of cultural evolution. However, there are as many possible definitions that are credited to the word "meme". For example, in the sense of computer simulation the term memetic algorithm is used to define a particular computational viewpoint. Memetics can be simply understood as a method for scientific analysis of cultural evolution. However, proponents of memetics as described in the Journal of Memetics – Evolutionary Models of Information Transmission believe that 'memetics' has the potential to be an important and promising analysis of culture using the framework of evolutionary concepts. Keith Henson who wrote Memetics and the Modular-Mind (Analog Aug. 1987) makes the case that memetics needs to incorporate Evolutionary psychology to understand the psychological traits of a meme's host. This is especially true of time-varying, meme-amplification host-traits, such as those leading to wars. See Evolutionary Psychology, Memes and the Origin of War. Recently, Christopher diCarlo has developed the idea of 'memetic equilibrium' to describe a cultural compatible state with biological equilibrium. In "Problem Solving and Neurotransmission in the Upper Paleolithic" (in press), diCarlo argues that as human consciousness evolved and developed, so too did our ancestors' capacity to consider and attempt to solve environmental problems in more conceptually sophisticated ways. Understood in this way, problem solving amongst a particular group, when considered satisfactory, often produces a feeling of environmental control, stability, in short--memetic equilibrium. But the pay-off is not merely practical, providing purely functional utility--it is biochemical and it comes in the form of neurotransmitters. The relationship between a gradually emerging conscious awareness and sophisticated languages in which to formulate representations combined with the desire to maintain biological equilibrium, generated the necessity for memetic equilibrium to fill in conceptual gaps in terms of understanding three very important aspects in the Upper Paleolithic: causality, morality, and mortality. The desire to explain phenomena in relation to maintaining survival and reproductive stasis, generated a normative stance in the minds of our ancestors—Survival/Reproductive Value (or S-R Value). The application of memetics to a difficult complex social system problem, environmental sustainability, has recently been attempted at thwink.org. Using meme types and memetic infection in several stock and flow simulation models, Jack Harich has demonstrated several interesting phenomena that are best, and perhaps only, explained by memes. One model, The Dueling Loops of the Political Powerplace, argues that the fundamental reason corruption is the norm in politics is due to an inherent structural advantage of one feedback loop pitted against another. Another model, The Memetic Evolution of Solutions to Difficult Problems, uses memes, the evolutionary algorithm, and the scientific method to show how complex solutions evolve over time and how that process can be improved. The insights gained from these models are being used to engineer memetic solution elements to the sustainability problem. Francis Heylighen of the Center Leo Apostel for Interdisciplinary Studies has postulated what he calls "memetic selection criteria". These criteria opened the way to a specialized field of applied memetics to find out if these selection criteria could stand the test of quantitative analyses. In 2003 Klaas Chielens carried out these tests in a Masters thesis project on the testability of the selection criteria. In Selfish Sounds and Linguistic Evolution (2004, Cambridge University Press), Austrian linguist Nikolaus Ritt has attempted to operationalise memetic concepts and use them for the explanation of long term sound changes and change conspiracies in early English. It is argued that a generalised Darwinian framework for handling cultural change can provide explanations where established, speaker centred approaches fail to do so. The book makes comparatively concrete suggestions about the possible material structure of memes, and provides two empirically rich case studies. In A Memetic Paradigm of Project Management (International Journal of Project Management, 23 (8) 575-583) Australian academic S.J. Whitty has argued that project management is a memeplex with the language and stories of its practitioners at its core. This radical, some say heretical approach requires project managers to consider that most of what they call a project and what it is to manage one is an illusion; a human construct about a collection of feelings, expectations, and sensations, cleverly conjured up, fashioned, and conveniently labelled by the human brain. It also requires project managers to consider that the reasons for using project management are not consciously driven to maximize profit. Project managers are required to consider project management as naturally occurring, self-serving, evolving and designing organizations for its own purpose. In “The Evolution of IT Innovations in Swedish Organizations: A Darwinian Critique of ‘Lamarckian’ Institutional Economics”, Journal of Evolutionary Economics, vol. 17, No. 1 (Feb 2007) Swedish political scientist Mikael Sandberg (Swedish political scientist) argues against "Lamarckian" interpretations of institutional and technological evolution and studies creative innovation of information technologies in governmental and private organizations in Sweden in the 1990s from a memetic perspective. Comparing the effects of active ("Lamarckian) IT strategy versus user–producer interactivity (Darwinian co-evolution), evidence from Swedish organizations shows that co-evolutionary interactivity is almost four times as strong a factor behind IT creativity as the ‘Lamarckian’ IT strategy. # Terminology - Memotype – is the actual information-content of a meme. - Meme-complex – (sometimes abbreviated memeplex) is a collection or grouping of memes that have evolved into a mutually supportive or symbiotic relationship. Simply put, a meme-complex is a set of ideas that reinforce each other. Meme-complexes are roughly analogous to the symbiotic collection of individual genes that make up the genetic codes of biological organisms. An example of a memeplex would be a religion. - Memeoid – is a neologism for people who have been taken over by a meme to the extent that their own survival becomes inconsequential. Examples include kamikazes, suicide bombers and cult members who commit mass suicide. The term was apparently coined by H. Keith Henson in "Memes, L5 and the Religion of the Space Colonies," L5 News, 1985 pp. 5-8, and referenced in the expanded second edition of Richard Dawkins' book The Selfish Gene (p. 330). - Memetic Equilibrium – refers to the cultural equivalent of species biological equilibrium. It is that which humans strive for in terms of personal value with respect to cultural artefacts and ideas. The term was coined by Christopher diCarlo in "Problem Solving and Neurotransmission in the Upper Paleolithic (in press).	Memetics Memetics is a neo-Darwinian approach to evolutionary models of cultural information transfer based on the concept of the meme. Started from a metaphor used in popular writings of Richard Dawkins, it has later turned into an approach in the study of self-replicating units of culture. It has been proposed that just as memes are analogous to genes, memetics is analogous to genetics. # History of the term In his book The Selfish Gene (1976), the ethologist Richard Dawkins used the term meme to describe a unit of human cultural transmission analogous to the gene, arguing that replication also happens in culture, albeit in a different sense. In his book, Dawkins contended that the meme is a unit of information residing in the brain and is the mutating replicator in human cultural evolution. It is a pattern that can influence its surroundings – that is, it has causal agency – and can propagate. This created great debate among sociologists, biologists, and scientists of other disciplines, because Dawkins himself did not provide a sufficient explanation of how the replication of units of information in the brain controls human behaviour and ultimately culture, since the principal topic of the book was genetics. Dawkins apparently did not intend to present a comprehensive theory of memetics in The Selfish Gene, but rather coined the term meme in a speculative spirit. Accordingly, the term "unit of information" came to be defined in different ways by many scientists. The modern memetics movement dates from the mid 1980s. A January 1983 Metamagical Themas column [1] by Douglas Hofstadter in Scientific American was influential as was his 1985 book of the same name. "Arel Lucas suggested that the discipline that studies memes and their connections to human and other carriers of them be known as memetics by analogy with 'genetics.'" [2] (This might not be the earliest use of "memetics.") The massive popular impact of Dawkins' The Selfish Gene has undoubtedly been an important factor in drawing in people of disparate intellectual backgrounds. Another crucial stimulus was the publication in 1992 of Consciousness Explained by Tufts University philosopher Daniel Dennett, which incorporated the meme concept into an influential theory of the mind. In his 1993 essay Viruses of the Mind, Richard Dawkins used memetics to explain the phenomenon of religious belief and the various characteristics of organised religions. However, the foundation of memetics in full modern incarnation originates in the publication in 1996, of two books by authors outside the academic mainstream: Virus of the Mind: The New Science of the Meme by former Microsoft executive turned motivational speaker and professional poker player, Richard Brodie, and Thought Contagion: How Belief Spreads Through Society by Aaron Lynch, a mathematician and philosopher who worked for many years as an engineer at Fermilab. Lynch claimed to have conceived his theory totally independently of any contact with academics in the cultural evolutionary sphere, and apparently was not even aware of Dawkins' The Selfish Gene until his book was very close to publication. Around the same time as the publication of the books by Lynch and Brodie, a new e-journal appeared on the web, hosted by the Centre for Policy Modelling at Manchester Metropolitan University Journal of Memetics – Evolutionary Models of Information Transmission. The journal has since then been taken over by Francis Heylighen of the CLEA research institute at the Vrije Universiteit Brussel. The e-journal soon became the central point for publication and debate within the nascent memetics community. (There had been a short-lived paper memetics publication starting in 1990, the Journal of Ideas edited by Elan Moritz. [3])[4]) In 1999, Susan Blackmore, a psychologist at the University of the West of England, published The Meme Machine, which more fully worked out the ideas of Dennett, Lynch and Brodie and attempted to compare and contrast them with various approaches from the cultural evolutionary mainstream, as well as providing novel, and controversial, memetic-based theories for the evolution of language and the human sense of individual selfhood. The term is a transliteration[citation needed] of the Ancient Greek Template:Unicode (Template:Unicode), meaning "imitator, pretender", and was used in 1904 by the German evolutionary biologist Richard Semon, best known for his development of the engram theory of memory, in his work Die mnemischen Empfindungen in ihren Beziehungen zu den Originalempfindungen, translated into English in 1921 as The Mneme. Until Daniel Schacter published Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory in 2000, Semon's work had little influence. # Internalists and externalists The memetics movement split almost immediately into those who want to stick to Dawkins' definition of a meme as "a unit of cultural transmission." Typical of this first group is Gibran Burchett, the founder of Aether Lumin Research firm, who has stated that a meme can be defined, more precisely, as a unit of cultural information ... located in the brain." A second group wants to redefine memes as observable cultural artifacts and behaviours. These two schools became known as the "internalists" and the "externalists." Prominent internalists included both Lynch and Brodie; the most vocal externalists included Derek Gatherer, a geneticist from Liverpool John Moores University and William Benzon, a writer on cultural evolution and music. The main rationale for externalism was that internal brain entities are not observable, and memetics cannot advance as a science, especially a quantitative science, unless it moves its emphasis onto the directly quantifiable aspects of culture. Internalists countered with various arguments: that brain states will eventually be directly observable with advanced technology, that most cultural anthropologists agree that culture is about beliefs and not artefacts, or that artefacts cannot be replicators in the same sense as mental entities (or DNA) are replicators. The debate became so heated that a 1998 Symposium on Memetics, organised as part of the 15th International Conference on Cybernetics, passed a motion calling for an end to definitional debates. The most advanced statement of the internalist school came in 2002 with the publication of The Electric Meme, by Robert Aunger, an anthropologist from the University of Cambridge. Aunger also organised a conference in Cambridge in 1999, at which prominent sociologists and anthropologists were able to give their assessment of the progress made in memetics to that date. This resulted in the publication of Darwinizing Culture: The Status of Memetics as a Science, edited by Aunger and with a foreword by Dennett, in 2000. # Maturity In 2005, the Journal of Memetics – Evolutionary Models of Information Transmission ceased publication and published a set of "obituaries" for memetics. This was not intended to suggest that there can be no further work on memetics. A relaunch of this journal is in the works and the journal is again accepting new submissions [1]. Susan Blackmore has left the University of the West of England to become a freelance science writer and now concentrates more on the field of consciousness and cognitive science. Derek Gatherer moved to work as a computer programmer in the pharmaceutical industry, although he still occasionally publishes on memetics-related matters. Richard Brodie is now climbing the world professional poker rankings. Aaron Lynch disowned the memetics community and the words "meme" and "memetics" (without disowning the ideas in his book), adopting the self-description "thought contagionist". Lynch lost his previous funding from a private sponsor and after his book royalties declined, he was unable to support himself as a private memetics/thought-contagion consultant. He died in 2005. Susan Blackmore (2002) re-stated the meme definition as whatever is copied from one person to another person, whether habits, skills, songs, stories, or any other kind of information. Further she said that memes, like genes, are replicators. That is, they are information that is copied with variation and selection. Because only some of the variants survive, memes (and hence human cultures) evolve. Memes are copied by imitation, teaching and other methods, and they compete for space in our memories and for the chance to be copied again. Large groups of memes that are copied and passed on together are called co-adapted meme complexes, or memeplexes. In her definition, thus, the way that a meme replicates is through imitation. This requires brain capacity to generally imitate a model or selectively imitate the model. Since the process of social learning varies from one person to another, the imitation process cannot be said to be completely imitated. The sameness of an idea may be expressed with different memes supporting it. This is to say that the mutation rate in memetic evolution is extremely high, and mutations are even possible within each and every interaction of the imitation process. It becomes very interesting when we see that a social system composed of a complex network of microinteractions exists, but at the macro level an order emerges to create culture. # Critique Benitez-Bribiesca, a critic to memetics, calls it "a pseudoscientific dogma" and "a dangerous idea that poses a threat to the serious study of conciousness and cultural evolution" among other things. As factual criticism, he refers to the lack of a code script for memes, as the DNA is for genes, and to the fact that the meme mutation mechanism (i.e., an idea going from one brain to another) is too unstable (low replication accuracy and high mutation rate), which would render the evolutionary process chaotic.[2] Another scientific critique comes from semiotics, (e.g., Deacon[3], Kull[4]) stating that the concept of meme is a primitivized concept of sign. Meme is thus described in memetics as a sign without its triadic nature. In other words, meme is a degenerate sign, which includes only its ability of being copied. Accordingly, the objects of copying are memes, whereas the objects of translation (sensu lato) and interpretation are signs. # New developments Dawkins responds in A Devil's Chaplain that there are actually two different types of memetic processes. The first is a type of cultural idea, action, or expression, which does have high variance; for instance, a student of his who had inherited some of the mannerisms of Wittgenstein. However, he also describes a self-correcting meme, highly resistant to mutation. As an example of this, he gives origami patterns in elementary schools – except in rare cases, the meme is either passed on in the exact sequence of instructions, or (in the case of a forgetful child) terminates. This type of meme tends not to evolve, and to experience profound mutations in the rare event that it does. Some memeticists, however, see this as more of a continuum of meme strength, rather than two types of memes. Another definition, given by Hokky Situngkir, tried to offer a more rigorous formalism for the meme, memeplexes, and the deme, seeing the meme as a cultural unit in a cultural complex system. It is based on the Darwinian genetic algorithm with some modifications to account for the different patterns of evolution seen in genes and memes. In the method of memetics as the way to see culture as a complex adaptive system, he describes a way to see memetics as an alternative methodology of cultural evolution. However, there are as many possible definitions that are credited to the word "meme". For example, in the sense of computer simulation the term memetic algorithm is used to define a particular computational viewpoint. Memetics can be simply understood as a method for scientific analysis of cultural evolution. However, proponents of memetics as described in the Journal of Memetics – Evolutionary Models of Information Transmission believe that 'memetics' has the potential to be an important and promising analysis of culture using the framework of evolutionary concepts. Keith Henson who wrote Memetics and the Modular-Mind (Analog Aug. 1987) [5] makes the case that memetics needs to incorporate Evolutionary psychology to understand the psychological traits of a meme's host. [6] This is especially true of time-varying, meme-amplification host-traits, such as those leading to wars. See Evolutionary Psychology, Memes and the Origin of War.[7] [8] Recently, Christopher diCarlo[9] has developed the idea of 'memetic equilibrium' to describe a cultural compatible state with biological equilibrium. In "Problem Solving and Neurotransmission in the Upper Paleolithic" (in press), diCarlo argues that as human consciousness evolved and developed, so too did our ancestors' capacity to consider and attempt to solve environmental problems in more conceptually sophisticated ways. Understood in this way, problem solving amongst a particular group, when considered satisfactory, often produces a feeling of environmental control, stability, in short--memetic equilibrium. But the pay-off is not merely practical, providing purely functional utility--it is biochemical and it comes in the form of neurotransmitters. The relationship between a gradually emerging conscious awareness and sophisticated languages in which to formulate representations combined with the desire to maintain biological equilibrium, generated the necessity for memetic equilibrium to fill in conceptual gaps in terms of understanding three very important aspects in the Upper Paleolithic: causality, morality, and mortality. The desire to explain phenomena in relation to maintaining survival and reproductive stasis, generated a normative stance in the minds of our ancestors—Survival/Reproductive Value (or S-R Value). The application of memetics to a difficult complex social system problem, environmental sustainability, has recently been attempted at thwink.org. Using meme types and memetic infection in several stock and flow simulation models, Jack Harich has demonstrated several interesting phenomena that are best, and perhaps only, explained by memes. One model, The Dueling Loops of the Political Powerplace, argues that the fundamental reason corruption is the norm in politics is due to an inherent structural advantage of one feedback loop pitted against another. Another model, The Memetic Evolution of Solutions to Difficult Problems, uses memes, the evolutionary algorithm, and the scientific method to show how complex solutions evolve over time and how that process can be improved. The insights gained from these models are being used to engineer memetic solution elements to the sustainability problem. Francis Heylighen of the Center Leo Apostel for Interdisciplinary Studies has postulated what he calls "memetic selection criteria". These criteria opened the way to a specialized field of applied memetics to find out if these selection criteria could stand the test of quantitative analyses. In 2003 Klaas Chielens carried out these tests in a Masters thesis project on the testability of the selection criteria. In Selfish Sounds and Linguistic Evolution (2004, Cambridge University Press), Austrian linguist Nikolaus Ritt has attempted to operationalise memetic concepts and use them for the explanation of long term sound changes and change conspiracies in early English. It is argued that a generalised Darwinian framework for handling cultural change can provide explanations where established, speaker centred approaches fail to do so. The book makes comparatively concrete suggestions about the possible material structure of memes, and provides two empirically rich case studies. In A Memetic Paradigm of Project Management (International Journal of Project Management, 23 (8) 575-583) Australian academic S.J. Whitty has argued that project management is a memeplex with the language and stories of its practitioners at its core. This radical, some say heretical approach requires project managers to consider that most of what they call a project and what it is to manage one is an illusion; a human construct about a collection of feelings, expectations, and sensations, cleverly conjured up, fashioned, and conveniently labelled by the human brain. It also requires project managers to consider that the reasons for using project management are not consciously driven to maximize profit. Project managers are required to consider project management as naturally occurring, self-serving, evolving and designing organizations for its own purpose. In “The Evolution of IT Innovations in Swedish Organizations: A Darwinian Critique of ‘Lamarckian’ Institutional Economics”, Journal of Evolutionary Economics, vol. 17, No. 1 (Feb 2007) Swedish political scientist Mikael Sandberg (Swedish political scientist) argues against "Lamarckian" interpretations of institutional and technological evolution and studies creative innovation of information technologies in governmental and private organizations in Sweden in the 1990s from a memetic perspective. Comparing the effects of active ("Lamarckian) IT strategy versus user–producer interactivity (Darwinian co-evolution), evidence from Swedish organizations shows that co-evolutionary interactivity is almost four times as strong a factor behind IT creativity as the ‘Lamarckian’ IT strategy. # Terminology - Memotype – is the actual information-content of a meme.[citation needed] - Meme-complex – (sometimes abbreviated memeplex) is a collection or grouping of memes that have evolved into a mutually supportive or symbiotic relationship.[citation needed] Simply put, a meme-complex is a set of ideas that reinforce each other. Meme-complexes are roughly analogous to the symbiotic collection of individual genes that make up the genetic codes of biological organisms. An example of a memeplex would be a religion. - Memeoid – is a neologism for people who have been taken over by a meme to the extent that their own survival becomes inconsequential. Examples include kamikazes, suicide bombers and cult members who commit mass suicide. The term was apparently coined by H. Keith Henson in "Memes, L5 and the Religion of the Space Colonies," L5 News, 1985 pp. 5-8, [10] and referenced in the expanded second edition of Richard Dawkins' book The Selfish Gene (p. 330). - Memetic Equilibrium – refers to the cultural equivalent of species biological equilibrium. It is that which humans strive for in terms of personal value with respect to cultural artefacts and ideas. The term was coined by Christopher diCarlo [11][12] in "Problem Solving and Neurotransmission in the Upper Paleolithic (in press).	https://www.wikidoc.org/index.php/Memetics
785a826b01265d1ca91a54a81c50f9e544349ba4	wikidoc	Menarche	Menarche # Overview Menarche (Template:IPAEng) is the first menstrual period, or first menstrual bleeding in the females of human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility. Timing of menarche is influenced by both genetic and environmental factors, especially nutritional status. The average age of menarche has declined over the last century but the magnitude of the decline and the factors responsible remain subjects of contention. The average age of menarche in the United States is about 12 years and 5 months. # Physiologic aspects ## Menarche as part of puberty Menarche is the culmination of a series of physiological and anatomic processes of puberty: - Attainment of a sufficient body mass (typically 17% body fat PMID 3117838). - Disinhibition of the GnRH pulse generator in the arcuate nucleus of the hypothalamus - Secretion of estrogen by the ovaries in response to pituitary hormones. - Over an interval of about 2 to 3 years, estrogen stimulates growth of the uterus (as well as height growth, breast growth, widening of the pelvis, and increased regional adipose tissue). - Estrogen stimulates growth and vascularity of the endometrium, the lining of the uterus. - Fluctuations of hormone levels can result in changes of adequacy of blood supply to parts of the endometrium. - Death of some of the endometrial tissue from these hormone or blood supply fluctuations leads to deciduation, a sloughing of part of the lining with some blood flow from the vagina. A specific hormonal signal for menarche is not known; menarche as a discrete event is thought to be the relatively chance result of the gradual thickening of the endometrium induced by rising but fluctuating pubertal estrogen. The menstruum, or "flow," consists of a combination of fresh and clotted blood with endometrial tissue. The initial flow of menarche is usually brighter red than mature menstrual flow. It is often scanty in amount and may be very brief, even a single instance of "spotting." Like other menses, menarche may be accompanied by abdominal cramping. ## Menarche and fertility In most girls, menarche does not signal that ovulation has occurred. Studies of American girls suggest that the average interval between menarche and ovulation is several months. Irregular, anovulatory menses commonly occur for 1-2 years or more before regular ovulation is established. Regular ovulation is usually indicated by predictable and consistent intervals between menses, predictable and consistent durations of menses, and predictable and consistent patterns of flow (e.g., heaviness or cramping). Continuing ovulation typically requires a body fat content of at least 22%. An anthropological term for this state of potential fertility is nubility. On the other hand, not every girl follows the typical pattern, and some girls ovulate before the first menstruation. Although unlikely, it is possible for a girl who has engaged in sexual intercourse shortly before her menarche to conceive and become pregnant, which would delay her menarche until after the birth. This goes against the widely held assumption that a woman cannot become pregnant until after menarche. ### Effects of stress and social environment on timing of menarche Some of the least understood environmental influences on timing of puberty are social and psychological. Nearly all of the research on these effects has concerned girls, partly because female puberty requires greater physiologic resources and partly because it involves a unique event (menarche) that makes survey research into female puberty much simpler than male. In most of these studies menarche was specifically examined, assuming it to be a valid "proxy" for the more general process of puberty. In comparison with the effects of genetics, nutrition, and general health, social influences are small, shifting timing by a few months rather than years. The most important part of a child's psychosocial environment is the family. Some of the aspects of family structure and function reported to be independently associated with earlier menarche: - The increased incidence of childhood obesity (reaching a body weight of 100 lbs or 45 kg appears to be an important "trigger" for the very young reaching menarche--both estrogen and progesterone are fat-soluble hormones). - Absence of father from the home from early childhood - High-conflict family relationships - Living in an urban environment Some of the aspects of family structure and function reported to be independently associated with later menarche: - Larger family size - Warmer, closer or more positive relationship with biological father - Warmer, more supportive, low-stress family environment - Having a number of older sisters Other research has focused on the effect of childhood stress on timing of puberty, especially female. Stress is a vague term and studies have examined conditions ranging from family tensions or conflict to wartime refugee status with threat to physical survival. The more dire social conditions have been found to be associated with delay of maturation, an effect that may be compounded by dietary inadequacy. There is more uncertainty and mixed evidence as to whether milder degrees of stress or early-life undernutrition can accelerate puberty in girls as would be predicted by life history theory and demonstrated in many other mammals. The understanding of these environmental effects is incomplete and the following observations and cautions are relevant: - Mechanisms of these social effects are unknown, though a variety of physiological processes, including pheromones, have been suggested based on animal research. - Most of these "effects" are statistical associations revealed by epidemiologic surveys. Statistical associations are not necessarily causal, and a variety of secondary variables and alternative explanations can be possibly intervening. Effects of such small size can never be confirmed or refuted for any individual child. - Despite the small magnitude of effect, interpretations of the data are politically controversial because of the ease with which this type of research can be used for political advocacy. Accusations of bias based on political agenda sometimes accompany scientific criticism. # Changes over time in the average age of menarche There were few systematic studies of timing of menarche before the latter half of the 20th century. Most older estimates of average timing of menarche were based on observation of a small homogeneous population not necessarily representative of the larger population, or based on recall by adult women, which is also susceptible to various forms of error. Most sources agree that the average age of menarche in girls in modern societies has declined, though the reasons and the degree remain subjects of controversy. There have been claims of a 2- to 2.5-year decline from about 1900 to the 1960s, but the best North American surveys reported only a 2-3 month decline from the mid-1970s to the mid-1990s. This is commonly attributed to larger body size and earlier average attainment of sufficient body fat, but other factors such as environmental exposure to chemicals that mimic estrogen or the urbanization and/or sexualization of Western society have also been considered as contributing factors. Less than 10% of U.S. girls start to menstruate before 11 years of age, and 90% of all US girls are menstruating by 13.75 years of age, with a median age of 12.43 years. This age at menarche is not significantly different (0.34 years earlier) than that reported for U.S. girls in 1973. Age at menarche for non-Hispanic black girls was significantly earlier than that of white girls at 10%, 25%, and 50% of those who had attained menarche, whereas Mexican American girls were only significantly earlier than the white girls at 25%. # Cultural aspects of menarche Menarche is celebrated in many cultures around the world as a rite of passage, a time to recognize that a girl is moving into womanhood. ## Rites of passage Some cultures have in past centuries have had rites of passage for a girl experiencing menarche. Africa - In the Tiv tribe in Nigeria, four lines are cut in the girl's abdomen, the practice of which is thought to make her a woman and more fertile. Asia, Australia, and Pacific Islands - In Australia, the Aborigines treat a girl to "love magic." The women teach her of the female powers and the physical changes marking womanhood. - When a Japanese girl has her first period, the family celebrates by eating red-colored rice and beans. - The Ulithi (oo-lith-ee) tribe of[Micronesia call a girl's menarche kufar (koo-faar); She goes to a menstrual house, where the women bathe her and recite spells. The girl then returns to the menstrual house when her next period comes. - Sri Lanka notes the time and day. An astrologer is contacted, who studies the star's alignment at the noted moment, in order to predict the girl's future. Her house is prepared for a ritual bathing, where the girl is scrubbed all over her body by the women of the family; she then is dressed in white. Printed invitations for a party are sent out, during which the girl receives money and special gifts. - In rural India, a girl who has reached puberty is given a ceremonial bath, decked with ornate jewels and garments, and the girl's kith and kin are all invited for a ceremony, in which it is announced that the girl has come of age and that celebrations follow. The tradition is quite nonexistent in urban India, although some families still hold on to this fast-disappearing tradition. North America - In the United States, rites of passage are rare, since girls are usually taught to keep aspects of sexual development private. Some families celebrate by giving the girl a card of congratulations, or even a candlelight ceremony. - The Navajo Indians have a celebration called kinaalda (kinn-all-duh). Girls run footraces to show strength. A cornmeal pudding is made for the tribe to taste. The girls who experience menarche wear special clothes and style their hair like the Navajo goddess "Changing Woman." - The Nootka Indians believe menarche to be a time for a physical strength test; the girl is taken out to sea and left alone. She is to swim back and is cheered upon returning to the shore of the village. - The Mescalero Apaches consider their menarche celebration the most important. Each year, an 8-day-long ceremony is celebrated in honor of each girl who began their period earlier that year. The first four days include feasting and dancing. Boy singers recount the history of the tribe each evening. The other four days are a private celebration during which girls have a private ceremony, reflecting on their passing into womanhood. # Medical aspects of menarche When menarche occurs, it confirms that the girl has had a gradual estrogen-induced growth of the uterus, especially the endometrium, and that the "outflow tract" from the uterus, through the cervix to the vagina, is open. In very rare instances, menarche may occur at an unusually early age, preceding thelarche and other signs of puberty. This is termed isolated premature menarche, but other causes of bleeding must be investigated and excluded. Growth is usually normal. Isolated premature menarche is rarely the first manifestation of precocious puberty. When menarche has failed to occur for more than 3 years after thelarche, or beyond 16 years of age, the delay is referred to as primary amenorrhea.	Menarche Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753 # Overview Menarche (Template:IPAEng) is the first menstrual period, or first menstrual bleeding in the females of human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility. Timing of menarche is influenced by both genetic and environmental factors, especially nutritional status. The average age of menarche has declined over the last century but the magnitude of the decline and the factors responsible remain subjects of contention. The average age of menarche in the United States is about 12 years and 5 months.[1] # Physiologic aspects ## Menarche as part of puberty Menarche is the culmination of a series of physiological and anatomic processes of puberty: - Attainment of a sufficient body mass (typically 17% body fat PMID 3117838). - Disinhibition of the GnRH pulse generator in the arcuate nucleus of the hypothalamus - Secretion of estrogen by the ovaries in response to pituitary hormones. - Over an interval of about 2 to 3 years, estrogen stimulates growth of the uterus (as well as height growth, breast growth, widening of the pelvis, and increased regional adipose tissue). - Estrogen stimulates growth and vascularity of the endometrium, the lining of the uterus. - Fluctuations of hormone levels can result in changes of adequacy of blood supply to parts of the endometrium. - Death of some of the endometrial tissue from these hormone or blood supply fluctuations leads to deciduation, a sloughing of part of the lining with some blood flow from the vagina. A specific hormonal signal for menarche is not known; menarche as a discrete event is thought to be the relatively chance result of the gradual thickening of the endometrium induced by rising but fluctuating pubertal estrogen. The menstruum, or "flow," consists of a combination of fresh and clotted blood with endometrial tissue. The initial flow of menarche is usually brighter red than mature menstrual flow. It is often scanty in amount and may be very brief, even a single instance of "spotting." Like other menses, menarche may be accompanied by abdominal cramping. ## Menarche and fertility In most girls, menarche does not signal that ovulation has occurred. Studies of American girls suggest that the average interval between menarche and ovulation is several months. Irregular, anovulatory menses commonly occur for 1-2 years or more before regular ovulation is established. Regular ovulation is usually indicated by predictable and consistent intervals between menses, predictable and consistent durations of menses, and predictable and consistent patterns of flow (e.g., heaviness or cramping). Continuing ovulation typically requires a body fat content of at least 22%. An anthropological term for this state of potential fertility is nubility. On the other hand, not every girl follows the typical pattern, and some girls ovulate before the first menstruation. Although unlikely, it is possible for a girl who has engaged in sexual intercourse shortly before her menarche to conceive and become pregnant, which would delay her menarche until after the birth. This goes against the widely held assumption that a woman cannot become pregnant until after menarche. ### Effects of stress and social environment on timing of menarche Some of the least understood environmental influences on timing of puberty are social and psychological. Nearly all of the research on these effects has concerned girls, partly because female puberty requires greater physiologic resources and partly because it involves a unique event (menarche) that makes survey research into female puberty much simpler than male. In most of these studies menarche was specifically examined, assuming it to be a valid "proxy" for the more general process of puberty. In comparison with the effects of genetics, nutrition, and general health, social influences are small, shifting timing by a few months rather than years. The most important part of a child's psychosocial environment is the family. Some of the aspects of family structure and function reported to be independently associated with earlier menarche: - The increased incidence of childhood obesity (reaching a body weight of 100 lbs or 45 kg appears to be an important "trigger" for the very young reaching menarche--both estrogen and progesterone are fat-soluble hormones). - Absence of father from the home from early childhood - High-conflict family relationships - Living in an urban environment Some of the aspects of family structure and function reported to be independently associated with later menarche: - Larger family size - Warmer, closer or more positive relationship with biological father - Warmer, more supportive, low-stress family environment - Having a number of older sisters Other research has focused on the effect of childhood stress on timing of puberty, especially female. Stress is a vague term and studies have examined conditions ranging from family tensions or conflict to wartime refugee status with threat to physical survival. The more dire social conditions have been found to be associated with delay of maturation, an effect that may be compounded by dietary inadequacy. There is more uncertainty and mixed evidence as to whether milder degrees of stress or early-life undernutrition can accelerate puberty in girls as would be predicted by life history theory and demonstrated in many other mammals. The understanding of these environmental effects is incomplete and the following observations and cautions are relevant: - Mechanisms of these social effects are unknown, though a variety of physiological processes, including pheromones, have been suggested based on animal research. - Most of these "effects" are statistical associations revealed by epidemiologic surveys. Statistical associations are not necessarily causal, and a variety of secondary variables and alternative explanations can be possibly intervening. Effects of such small size can never be confirmed or refuted for any individual child. - Despite the small magnitude of effect, interpretations of the data are politically controversial because of the ease with which this type of research can be used for political advocacy. Accusations of bias based on political agenda sometimes accompany scientific criticism. # Changes over time in the average age of menarche There were few systematic studies of timing of menarche before the latter half of the 20th century. Most older estimates of average timing of menarche were based on observation of a small homogeneous population not necessarily representative of the larger population, or based on recall by adult women, which is also susceptible to various forms of error. Most sources agree that the average age of menarche in girls in modern societies has declined, though the reasons and the degree remain subjects of controversy. There have been claims of a 2- to 2.5-year decline from about 1900 to the 1960s, but the best North American surveys reported only a 2-3 month decline from the mid-1970s to the mid-1990s. This is commonly attributed to larger body size and earlier average attainment of sufficient body fat, but other factors such as environmental exposure to chemicals that mimic estrogen or the urbanization and/or sexualization of Western society have also been considered as contributing factors. Less than 10% of U.S. girls start to menstruate before 11 years of age, and 90% of all US girls are menstruating by 13.75 years of age, with a median age of 12.43 years. This age at menarche is not significantly different (0.34 years earlier) than that reported for U.S. girls in 1973. Age at menarche for non-Hispanic black girls was significantly earlier than that of white girls at 10%, 25%, and 50% of those who had attained menarche, whereas Mexican American girls were only significantly earlier than the white girls at 25%.[2] # Cultural aspects of menarche Menarche is celebrated in many cultures around the world as a rite of passage, a time to recognize that a girl is moving into womanhood. ## Rites of passage Some cultures have in past centuries have had rites of passage for a girl experiencing menarche. Africa - In the Tiv tribe in Nigeria, four lines are cut in the girl's abdomen, the practice of which is thought to make her a woman and more fertile. Asia, Australia, and Pacific Islands - In Australia, the Aborigines treat a girl to "love magic." The women teach her of the female powers and the physical changes marking womanhood. - When a Japanese girl has her first period, the family celebrates by eating red-colored rice and beans. - The Ulithi (oo-lith-ee) tribe of[Micronesia call a girl's menarche kufar (koo-faar); She goes to a menstrual house, where the women bathe her and recite spells. The girl then returns to the menstrual house when her next period comes. - Sri Lanka notes the time and day. An astrologer is contacted, who studies the star's alignment at the noted moment, in order to predict the girl's future. Her house is prepared for a ritual bathing, where the girl is scrubbed all over her body by the women of the family; she then is dressed in white. Printed invitations for a party are sent out, during which the girl receives money and special gifts. - In rural India, a girl who has reached puberty is given a ceremonial bath, decked with ornate jewels and garments, and the girl's kith and kin are all invited for a ceremony, in which it is announced that the girl has come of age and that celebrations follow. The tradition is quite nonexistent in urban India, although some families still hold on to this fast-disappearing tradition. North America - In the United States, rites of passage are rare, since girls are usually taught to keep aspects of sexual development private. Some families celebrate by giving the girl a card of congratulations, or even a candlelight ceremony. - The Navajo Indians have a celebration called kinaalda (kinn-all-duh). Girls run footraces to show strength. A cornmeal pudding is made for the tribe to taste. The girls who experience menarche wear special clothes and style their hair like the Navajo goddess "Changing Woman." - The Nootka Indians believe menarche to be a time for a physical strength test; the girl is taken out to sea and left alone. She is to swim back and is cheered upon returning to the shore of the village. - The Mescalero Apaches consider their menarche celebration the most important. Each year, an 8-day-long ceremony is celebrated in honor of each girl who began their period earlier that year. The first four days include feasting and dancing. Boy singers recount the history of the tribe each evening. The other four days are a private celebration during which girls have a private ceremony, reflecting on their passing into womanhood. # Medical aspects of menarche When menarche occurs, it confirms that the girl has had a gradual estrogen-induced growth of the uterus, especially the endometrium, and that the "outflow tract" from the uterus, through the cervix to the vagina, is open. In very rare instances, menarche may occur at an unusually early age, preceding thelarche and other signs of puberty. This is termed isolated premature menarche, but other causes of bleeding must be investigated and excluded. Growth is usually normal.[3] Isolated premature menarche is rarely the first manifestation of precocious puberty. When menarche has failed to occur for more than 3 years after thelarche, or beyond 16 years of age, the delay is referred to as primary amenorrhea.	https://www.wikidoc.org/index.php/Menarche
c2ee677fe3bc88771d50902481102e21cdd96c7c	wikidoc	Mequinol	Mequinol # Overview Mequinol, or 4-Methoxyphenol, is a phenol used in dermatology and organic chemistry. # Uses ## Dermatology Mequinol is a common active ingredient in topical drugs used for skin depigmentation. As a topical drug Mequinol is often mixed with tretinoin, a topical retinoid. A common formulation for this drug is an ethanolic solution of 2% Mequinol and 0.01% tretinoin by mass. Dermatologists commonly prescribe the drug to treat solar lentigines, liver spots, or age spots. Lower dosages of mequinol have been used in conjunction with a Q-switched laser to depigment skin in patients with disseminated idiopathic vitiligo. ## Organic chemistry In organic chemistry 4-Methoxyphenol is used to inhibit the radical polymerization of monomers (e.g. acrylates or styrene monomers). # Preparation 4-Methoxyphenol is produced from p-benzoquinone and methanol via a free radical reaction.	Mequinol Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Mequinol, or 4-Methoxyphenol, is a phenol used in dermatology[1] and organic chemistry.[2] # Uses ## Dermatology Mequinol is a common active ingredient in topical drugs used for skin depigmentation. As a topical drug Mequinol is often mixed with tretinoin, a topical retinoid. A common formulation for this drug is an ethanolic solution of 2% Mequinol and 0.01% tretinoin by mass.[1] Dermatologists commonly prescribe the drug to treat solar lentigines, liver spots, or age spots. Lower dosages of mequinol have been used in conjunction with a Q-switched laser to depigment skin in patients with disseminated idiopathic vitiligo.[3] ## Organic chemistry In organic chemistry 4-Methoxyphenol is used to inhibit the radical polymerization of monomers (e.g. acrylates or styrene monomers).[2] # Preparation 4-Methoxyphenol is produced from p-benzoquinone and methanol via a free radical reaction.[4][5]	https://www.wikidoc.org/index.php/Mequinol
0f732dd6204f5e78b498336ef57b16fc047148c3	wikidoc	Mesoderm	Mesoderm # Overview The germ layer mesoderm forms in the embryos of animals more complex than cnidarians, making them triploblastic. Mesoderm forms during gastrulation when some of the cells migrating inward to form the endoderm form an additional layer between the endoderm and the ectoderm. This key innovation evolved hundreds of millions of years ago and led to the evolution of nearly all large, complex animals. The formation of a mesoderm led to the formation of a coelom. Organs formed inside a coelom (body cavity) can freely move, grow, and develop independently of the body wall while fluid cushions and protects them from shocks. # Categorizing animals Not all triploblastic animals have a coelom, like the simplest animals with organs that form from three tissue layers: flatworms. Three different configurations of mesoderm in relation to ectoderm form a method of categorizing animals. - Acoelomates no coelom tissues and organs packed between gut and body wall - no coelom - tissues and organs packed between gut and body wall - Pseudocoelomates false coelom unlined or partially lined body cavity between gut and body wall - false coelom - unlined or partially lined body cavity between gut and body wall - Coelomates proper coelom lined cavity between gut and body wall - proper coelom - lined cavity between gut and body wall # Derivatives ## General Note: Not all triploblasts produce all of the items listed. - bones - most of the circulatory system, including the heart and major blood vessels - connective tissues of the gut and integuments - mesenchyme - mesothelium - muscles - peritoneum (lining of the coelom) - reproductive system - urinary system, including the kidneys ## Vertebrates In addition to the general list, the mesoderm of a developing vertebrate differentiates into the following: - Chordamesoderm - Paraxial mesoderm - Intermediate mesoderm - Lateral plate mesoderm	Mesoderm Template:Infobox Embryology Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview The germ layer mesoderm forms in the embryos of animals more complex than cnidarians, making them triploblastic. Mesoderm forms during gastrulation when some of the cells migrating inward to form the endoderm form an additional layer between the endoderm and the ectoderm. This key innovation evolved hundreds of millions of years ago and led to the evolution of nearly all large, complex animals. The formation of a mesoderm led to the formation of a coelom. Organs formed inside a coelom (body cavity) can freely move, grow, and develop independently of the body wall while fluid cushions and protects them from shocks. # Categorizing animals Not all triploblastic animals have a coelom, like the simplest animals with organs that form from three tissue layers: flatworms. Three different configurations of mesoderm in relation to ectoderm form a method of categorizing animals. - Acoelomates no coelom tissues and organs packed between gut and body wall - no coelom - tissues and organs packed between gut and body wall - Pseudocoelomates false coelom unlined or partially lined body cavity between gut and body wall - false coelom - unlined or partially lined body cavity between gut and body wall - Coelomates proper coelom lined cavity between gut and body wall - proper coelom - lined cavity between gut and body wall # Derivatives ## General Note: Not all triploblasts produce all of the items listed. - bones - most of the circulatory system, including the heart and major blood vessels - connective tissues of the gut and integuments - mesenchyme - mesothelium - muscles - peritoneum (lining of the coelom) - reproductive system - urinary system, including the kidneys ## Vertebrates In addition to the general list, the mesoderm of a developing vertebrate differentiates into the following: - Chordamesoderm - Paraxial mesoderm - Intermediate mesoderm - Lateral plate mesoderm	https://www.wikidoc.org/index.php/Mesoderm
6368b4f9d79e86933fc35bfb121dda32c24df17e	wikidoc	Xanthine	Xanthine # Overview Xanthine (3,7-dihydro-purine-2,6-dione), is a purine base found in most body tissues and fluids and in other organisms. # Reactions Xanthine is a product on the pathway of purine degradation. - It is created from guanine by guanine deaminase. - It is created from hypoxanthine by xanthine oxidoreductase. Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme. # Pathology People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid. # Clinical significance of xanthine derivatives Derivatives of xanthine, known collectively as xanthines, are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. On the contrary, they really only eliminate the actions of adenosine to some extent, adenosine causing sleepiness, thus they are by far less in effectiveness as stimulants than sympathomimetic amines. Their effects, however, are widespread and their therapeutic range is narrow, so they are not the drug of choice in asthma treatment. Therapeutic level is 10-20 micrograms/mL blood. Signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia. Methylated xanthine derivatives include caffeine, paraxanthine, theophylline, and theobromine (found mainly in chocolate). These drugs inhibit phosphodiesterase and antagonise adenosine. Xanthines are also found very rarely as constituents of nucleic acids.	Xanthine Template:Chembox new Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Xanthine (3,7-dihydro-purine-2,6-dione), is a purine base found in most body tissues and fluids and in other organisms. # Reactions Xanthine is a product on the pathway of purine degradation. - It is created from guanine by guanine deaminase. - It is created from hypoxanthine by xanthine oxidoreductase. Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme. # Pathology People with the rare genetic disorder xanthinuria lack sufficient xanthine oxidase and cannot convert xanthine to uric acid. # Clinical significance of xanthine derivatives Derivatives of xanthine, known collectively as xanthines, are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. On the contrary, they really only eliminate the actions of adenosine to some extent, adenosine causing sleepiness, thus they are by far less in effectiveness as stimulants than sympathomimetic amines. Their effects, however, are widespread and their therapeutic range is narrow, so they are not the drug of choice in asthma treatment. Therapeutic level is 10-20 micrograms/mL blood. Signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia. Methylated xanthine derivatives include caffeine, paraxanthine, theophylline, and theobromine (found mainly in chocolate). These drugs inhibit phosphodiesterase and antagonise adenosine. Xanthines are also found very rarely as constituents of nucleic acids.	https://www.wikidoc.org/index.php/Methylxanthine
b53cbfa5ae3661e8cff8bdd84fdd4e75428fcf73	wikidoc	microRNA	microRNA # Overview In genetics, microRNAs (miRNA) are single-stranded RNA molecules of about 21-23 nucleotides in length, which regulate gene expression. miRNAs are encoded by genes that are transcribed from DNA but not translated into protein (non-coding RNA); instead they are processed from primary transcripts known as pri-miRNA to short stem-loop structures called pre-miRNA and finally to functional miRNA. Mature miRNA molecules are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to downregulate gene expression. They were first described in 1993 by Lee and colleagues , yet the term microRNA was only introduced in 2001 in a set of three articles in Science (26 October 2001). # Formation and processing The genes encoding miRNAs are much longer than the processed mature miRNA molecule; miRNAs are first transcribed as primary transcripts or pri-miRNA with a cap and poly-A tail and processed to short, 70-nucleotide stem-loop structures known as pre-miRNA in the cell nucleus. This processing is performed in animals by a protein complex known as the Microprocessor complex, consisting of the nuclease Drosha and the double-stranded RNA binding protein Pasha. These pre-miRNAs are then processed to mature miRNAs in the cytoplasm by interaction with the endonuclease Dicer, which also initiates the formation of the RNA-induced silencing complex (RISC). This complex is responsible for the gene silencing observed due to miRNA expression and RNA interference. The pathway in plants varies slightly due to their lack of Drosha homologs; instead, Dicer homologs alone effect several processing steps. Zeng et al. have shown that efficient processing of pre-miRNA by Drosha requires presence of extended single-stranded RNA on both 3'- and 5'-ends of hairpin molecule. They demonstrated that these motifs could be of different composition while their length is of high importance if processing is to take place at all. Their findings were confirmed in another work by Han et al. Using bioinformatics tools Han et al. analysed folding of 321 human and 68 fly pri-miRNAs. 280 human and 55 fly pri-miRNAs were selected for further study, excluding those molecules whose folding showed presence of multiple loops. All human and fly pri-miRNA contained very similar structural regions, which authors called 'basal segments', 'lower stem', 'upper stem' and 'terminal loop'. Based on the encoding position of miRNA, i.e. in the 5'-strand (5'-donors) or 3'-strand (3'-donors), thermodynamic profiles of pri-miRNA were determined. Following experiments have shown that Drosha complex cleaves RNA molecule ~2 helical turns away from the terminal loop and ~1 turn away from basal segments. In most analysed molecules this region contains unpaired nucleotides and the free energy of the duplex is relatively high compared to lower and upper stem regions. Most pre-miRNAs don't have a perfect double-stranded RNA (dsRNA) structure topped by a terminal loop. There are few possible explanations for such selectivity. One could be that dsRNAs longer than 21 base pairs activate interferon response and anti-viral machinery in the cell. Another plausible explanation could be that thermodynamical profile of pre-miRNA determines which strand will be incorporated into Dicer complex. Indeed, aforementioned study by Han et al. demonstrated very clear similarities between pri-miRNAs encoded in respective (5'- or 3'-) strands. When Dicer cleaves the pre-miRNA stem-loop, two complementary short RNA molecules are formed, but only one is integrated into the RISC complex. This strand is known as the guide strand and is selected by the argonaute protein, the catalytically active RNase in the RISC complex, on the basis of the stability of the 5' end. The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate. After integration into the active RISC complex, miRNAs base pair with their complementary mRNA molecules and induce mRNA degradation by argonaute proteins, the catalytically active members of the RISC complex. It is as yet unclear how the activated RISC complex locates the mRNA targets in the cell, though it has been shown that the process is not coupled to ongoing protein translation from the mRNA. # Cellular functions The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is complementary to a part of one or more messenger RNAs (mRNAs). Animal miRNAs are usually complementary to a site in the 3' UTR whereas plant miRNAs are usually complementary to coding regions of mRNAs. The annealing of the miRNA to the mRNA then inhibits protein translation, but sometimes facilitates cleavage of the mRNA. This is thought to be the primary mode of action of plant miRNAs. In such cases, the formation of the double-stranded RNA through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to RNA interference (RNAi), though in other cases it is believed that the miRNA complex blocks the protein translation machinery or otherwise prevents protein translation without causing the mRNA to be degraded. miRNAs may also target methylation of genomic sites which correspond to targeted mRNAs. miRNAs function in association with a complement of proteins collectively termed the miRNP. This effect was first described for the worm C. elegans in 1993 by Victor Ambros and coworkers (Lee et al., 1993). As of 2002, miRNAs have been confirmed in various plants and animals, including C. elegans, human and the plant Arabidopsis thaliana. Genes have been found in bacteria that are similar in the sense that they control mRNA abundance or translation by binding an mRNA by base pairing, however they are not generally considered to be miRNAs because the Dicer enzyme is not involved. In plants, similar RNA species termed short-interfering RNAs siRNAs are used to prevent the transcription of viral RNA. While this siRNA is double-stranded, the mechanism seems to be closely related to that of miRNA, especially taking the hairpin structures into account. siRNAs are also used to regulate cellular genes, as miRNAs do. # Detecting and manipulating miRNA signalling The activity of an miRNA can be experimentally blocked using a locked nucleic acid oligo, a Morpholino oligo -r a 2'-O-methyl RNA oligo. Steps in the maturation of miRNAs can be blocked by steric-blocking oligos. The target site of an miRNA on an mRNA can be blocked by a steric blocking oligo. # miRNA and cancer miRNA has been found to have links with some types of cancer. A study of mice altered to produce excess c-myc — a protein implicated in several cancers — shows that miRNA has an effect on the development of cancer. Mice that were engineered to produce a surplus of types of miRNA found in lymphoma cells developed the disease within 50 days and died two weeks later. In contrast, mice without the surplus miRNA lived over 100 days. Another study found that two types of miRNA inhibit the E2F1 protein, which regulates cell proliferation. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch genes on and off. By measuring activity among 217 genes encoding miRNA, patterns of gene activity that can distinguish types of cancers can be discerned. miRNA signatures may enable classification of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with chronic lymphocytic leukemia had slow growing or aggressive forms of the cancer. # miRNA and heart disease miRNA has been shown to be related to heart disease. Mice were created that were deficient in a muscle-specific miRNA and these mice had high rate of the most common congenital heart disease -- ventricular septal defects characterized by the holes between the left and the right ventricles of the heart. Such mice also show hyperplasia (an increase of the number of cardiac muscle cells that leads to heart enlargement) and abnormalities in cardiac conduction.	microRNA # Overview In genetics, microRNAs (miRNA) are single-stranded RNA molecules of about 21-23 nucleotides in length, which regulate gene expression. miRNAs are encoded by genes that are transcribed from DNA but not translated into protein (non-coding RNA); instead they are processed from primary transcripts known as pri-miRNA to short stem-loop structures called pre-miRNA and finally to functional miRNA. Mature miRNA molecules are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to downregulate gene expression. They were first described in 1993 by Lee and colleagues [1], yet the term microRNA was only introduced in 2001 in a set of three articles in Science (26 October 2001).[2] # Formation and processing The genes encoding miRNAs are much longer than the processed mature miRNA molecule; miRNAs are first transcribed as primary transcripts or pri-miRNA with a cap and poly-A tail and processed to short, 70-nucleotide stem-loop structures known as pre-miRNA in the cell nucleus. This processing is performed in animals by a protein complex known as the Microprocessor complex, consisting of the nuclease Drosha and the double-stranded RNA binding protein Pasha.[3] These pre-miRNAs are then processed to mature miRNAs in the cytoplasm by interaction with the endonuclease Dicer, which also initiates the formation of the RNA-induced silencing complex (RISC).[4] This complex is responsible for the gene silencing observed due to miRNA expression and RNA interference. The pathway in plants varies slightly due to their lack of Drosha homologs; instead, Dicer homologs alone effect several processing steps.[5] Zeng et al. have shown that efficient processing of pre-miRNA by Drosha requires presence of extended single-stranded RNA on both 3'- and 5'-ends of hairpin molecule[citation needed]. They demonstrated that these motifs could be of different composition while their length is of high importance if processing is to take place at all. Their findings were confirmed in another work by Han et al[citation needed]. Using bioinformatics tools Han et al. analysed folding of 321 human and 68 fly pri-miRNAs. 280 human and 55 fly pri-miRNAs were selected for further study, excluding those molecules whose folding showed presence of multiple loops. All human and fly pri-miRNA contained very similar structural regions, which authors called 'basal segments', 'lower stem', 'upper stem' and 'terminal loop'. Based on the encoding position of miRNA, i.e. in the 5'-strand (5'-donors) or 3'-strand (3'-donors), thermodynamic profiles of pri-miRNA were determined[citation needed]. Following experiments have shown that Drosha complex cleaves RNA molecule ~2 helical turns away from the terminal loop and ~1 turn away from basal segments. In most analysed molecules this region contains unpaired nucleotides and the free energy of the duplex is relatively high compared to lower and upper stem regions[citation needed]. Most pre-miRNAs don't have a perfect double-stranded RNA (dsRNA) structure topped by a terminal loop. There are few possible explanations for such selectivity. One could be that dsRNAs longer than 21 base pairs activate interferon response and anti-viral machinery in the cell. Another plausible explanation could be that thermodynamical profile of pre-miRNA determines which strand will be incorporated into Dicer complex. Indeed, aforementioned study by Han et al. demonstrated very clear similarities between pri-miRNAs encoded in respective (5'- or 3'-) strands. When Dicer cleaves the pre-miRNA stem-loop, two complementary short RNA molecules are formed, but only one is integrated into the RISC complex. This strand is known as the guide strand and is selected by the argonaute protein, the catalytically active RNase in the RISC complex, on the basis of the stability of the 5' end.[6] The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate.[7] After integration into the active RISC complex, miRNAs base pair with their complementary mRNA molecules and induce mRNA degradation by argonaute proteins, the catalytically active members of the RISC complex. It is as yet unclear how the activated RISC complex locates the mRNA targets in the cell, though it has been shown that the process is not coupled to ongoing protein translation from the mRNA.[8] # Cellular functions The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is complementary to a part of one or more messenger RNAs (mRNAs). Animal miRNAs are usually complementary to a site in the 3' UTR whereas plant miRNAs are usually complementary to coding regions of mRNAs. The annealing of the miRNA to the mRNA then inhibits protein translation, but sometimes facilitates cleavage of the mRNA. This is thought to be the primary mode of action of plant miRNAs. In such cases, the formation of the double-stranded RNA through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to RNA interference (RNAi), though in other cases it is believed that the miRNA complex blocks the protein translation machinery or otherwise prevents protein translation without causing the mRNA to be degraded. miRNAs may also target methylation of genomic sites which correspond to targeted mRNAs. miRNAs function in association with a complement of proteins collectively termed the miRNP. This effect was first described for the worm C. elegans in 1993 by Victor Ambros and coworkers (Lee et al., 1993). As of 2002, miRNAs have been confirmed in various plants and animals, including C. elegans, human and the plant Arabidopsis thaliana. Genes have been found in bacteria that are similar in the sense that they control mRNA abundance or translation by binding an mRNA by base pairing, however they are not generally considered to be miRNAs because the Dicer enzyme is not involved. In plants, similar RNA species termed short-interfering RNAs siRNAs are used to prevent the transcription of viral RNA. While this siRNA is double-stranded, the mechanism seems to be closely related to that of miRNA, especially taking the hairpin structures into account. siRNAs are also used to regulate cellular genes, as miRNAs do. # Detecting and manipulating miRNA signalling The activity of an miRNA can be experimentally blocked using a locked nucleic acid oligo, a Morpholino oligo[9][10] or a 2'-O-methyl RNA oligo[11]. Steps in the maturation of miRNAs can be blocked by steric-blocking oligos[12]. The target site of an miRNA on an mRNA can be blocked by a steric blocking oligo[13][14]. # miRNA and cancer miRNA has been found to have links with some types of cancer. A study of mice altered to produce excess c-myc — a protein implicated in several cancers — shows that miRNA has an effect on the development of cancer. Mice that were engineered to produce a surplus of types of miRNA found in lymphoma cells developed the disease within 50 days and died two weeks later. In contrast, mice without the surplus miRNA lived over 100 days.[15] Another study found that two types of miRNA inhibit the E2F1 protein, which regulates cell proliferation. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch genes on and off.[16] By measuring activity among 217 genes encoding miRNA, patterns of gene activity that can distinguish types of cancers can be discerned. miRNA signatures may enable classification of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with chronic lymphocytic leukemia had slow growing or aggressive forms of the cancer.[17] # miRNA and heart disease miRNA has been shown to be related to heart disease.[18] Mice were created that were deficient in a muscle-specific miRNA and these mice had high rate of the most common congenital heart disease -- ventricular septal defects characterized by the holes between the left and the right ventricles of the heart. Such mice also show hyperplasia (an increase of the number of cardiac muscle cells that leads to heart enlargement) and abnormalities in cardiac conduction.	https://www.wikidoc.org/index.php/Micro-RNA
0be9fd99e861a76debf8058f95f16bda4335d15a	wikidoc	Mimosine	Mimosine Mimosine is an alkaloid, β-3-hydroxy-4 pyridone amino acid. It is a toxic non-protein free amino acid otherwise chemically similar to tyrosine, and was first isolated from Mimosa pudica. In ruminants, mimosine is degraded to 3,4 and 2,3 dihydroxy pyridone (3,4- and 2,3-DHP). It occurs in a few other Mimosa spp. and all members of the closed allied genus Leucaena. Although toxicosis has occurred in Australia, Papua New Guinea, Africa and Florida, it has not been recorded in any other tropical and subtropical regions. Goats in Myanmar lost hair when fed to diet containing 50 % of leucaena. Goats and cattle in Hawaii are able to degrade the 3,4-DHP ruminally. Tolerance might be related to the presence or absence of microbes tolerant to mimosine and 3,4-DHP. It is known that at least Australian goats do not share the abilities of their Hawaiian counterparts. The initial population of bacteria inoculated was not a pure culture. From this mixed culture, pure colonies of bacteria with ability to degrade the two isomers of DHP, 3,4 and 2,3 were isolated. Initially named strain 78-1 (ATCC 49833), it is strictly anaerobic when growing, can be stored at 20 °C and will tolerate temperatures up to 50 °C, above which it is killed. The substrates they ferment, their cell wall composition, and rRNA sequences clearly show that these bacteria are not closely related to any other in the rumen. Thus it has been assigned to a new genus and called Synergestes jonesii (Allison et al., 1992) in honour of R. J. Jones. A similar bacterium has been isolated from sheep and cattle in Venezuela and another in India.Aung from Myanmar also found new bacteria which can degrade mimosine. Attempts to transinoculate rumen liquor from goats to sheep in India have failed to improve mimosine metabolism in the latter.	Mimosine Mimosine is an alkaloid, β-3-hydroxy-4 pyridone amino acid. It is a toxic non-protein free amino acid otherwise chemically similar to tyrosine, and was first isolated from Mimosa pudica. In ruminants, mimosine is degraded to 3,4 and 2,3 dihydroxy pyridone (3,4- and 2,3-DHP). It occurs in a few other Mimosa spp. and all members of the closed allied genus Leucaena. Although toxicosis has occurred in Australia, Papua New Guinea, Africa and Florida, it has not been recorded in any other tropical and subtropical regions. Goats in Myanmar lost hair when fed to diet containing 50 % of leucaena. Goats and cattle in Hawaii are able to degrade the 3,4-DHP ruminally. Tolerance might be related to the presence or absence of microbes tolerant to mimosine and 3,4-DHP. It is known that at least Australian goats do not share the abilities of their Hawaiian counterparts. The initial population of bacteria inoculated was not a pure culture. From this mixed culture, pure colonies of bacteria with ability to degrade the two isomers of DHP, 3,4 and 2,3 were isolated. Initially named strain 78-1 (ATCC 49833), it is strictly anaerobic when growing, can be stored at 20 °C and will tolerate temperatures up to 50 °C, above which it is killed. The substrates they ferment, their cell wall composition, and rRNA sequences clearly show that these bacteria are not closely related to any other in the rumen. Thus it has been assigned to a new genus and called Synergestes jonesii (Allison et al., 1992) in honour of R. J. Jones. A similar bacterium has been isolated from sheep and cattle in Venezuela and another in India.Aung from Myanmar also found new bacteria which can degrade mimosine.[citation needed] Attempts to transinoculate rumen liquor from goats to sheep in India have failed to improve mimosine metabolism in the latter.[1]	https://www.wikidoc.org/index.php/Mimosine
3cfb8167c1c2f7648ca27eb639f9058e363f7c4d	wikidoc	Prazosin	Prazosin # 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 Prazosin is a alpha-adrenergic blocker that is FDA approved for the {{{indicationType}}} of hypertension. Common adverse reactions include orthostatic hypotension, palpitations, nausea, asthenia, dizziness, headache, lethargy and somnolence. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Initial dose: - 1 mg two or three times a day - Maintenance dose: - Dosage may be slowly increased to a total daily dose of 20 mg given in divided doses. The therapeutic dosages most commonly employed have ranged from 6 mg to 15 mg daily given in divided doses. Doses higher than 20 mg usually do not increase efficacy, however a few patients may benefit from further increases up to a daily dose of 40 mg given in divided doses. After initial titration some patients can be maintained adequately on a twice daily dosage regimen. - Use with other drugs: - When adding a diuretic or other antihypertensive agent, the dose of prazosin should be reduced to 1 mg or 2 mg three times a day and retitration then carried out. - Concomitant administration of prazosin with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking prazosin. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Prazosin in adult patients. ### Non–Guideline-Supported Use - Prazosin has been used in the treatment benign prostatic hyperplasia. - Prazosin has been successfully used in the hemodynamic management of patients with congestive heart failure. - A 6-week open-label trial, with 5 patients, with history of exposure to civilian trauma, in a non-military environment, who subsequently developed posttraumatic stress disorder (PTSD): - 1 to 4 mg/day - An 8-week open-label trial, with 4 patients, with history of combat trauma nightmares and chronic DSM-IV posttraumatic stress disorder (PTSD) with concomitant severe intractable combat trauma nightmares: - 2 to 10 mg/day - The association of alprostadil and prazosin is an effective option for the treatment of erectile dysfunction. - The therapeutic response to prazosin proved to be better than the placebo response for the following dosages of prazosin: - 250, 500, 1000, and 2000 micrograms - A study shows that there is benefit in the use of prazosin in cases of envenomation by the Indian red scorpion, showed by the reduction of morbidity, mortality, and recovery time. - 0.5 mg every 6 hours, until improvement of the clinical status. - According to a double-blind study, Prazosin shows therapeutic benefit when compared to the placebo, for the treatment of Raynaud phenomenon. - 1 mg orally 3 times/day # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding FDA-Label indications Use of Prazosin in pediatric patients. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Prazosin in pediatric patients. ### Non–Guideline-Supported Use - A study shows that there is benefit in the use of prazosin in cases of envenomation by the Indian red scorpion, showed by the reduction of morbidity, mortality, and recovery time. - 0.25 mg every 6 hours, until improvement of the clinical status. # Contraindications - Prazosin is contraindicated in patients with known sensitivity to: - Quinazolines - Prazosin - Any of the inert ingredients # Warnings - Prazosin, as other alpha-blockers, may cause: - Syncope with sudden loss of consciousness: - May be due to an excessive postural hypotensive effect - Occasionally the syncopal episode has been preceded by a bout of severe tachycardia with heart rates of 120–160 beats per minute - Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug - These have often been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of prazosin. - The incidence of syncopal episodes is approximately 1% in patients given an initial dose of 2 mg or greater. - Clinical trials conducted during the investigational phase of this drug suggest that syncopal episodes can be minimized by limiting the initial dose of the drug to 1 mg, by subsequently increasing the dosage slowly, and by introducing any additional antihypertensive drugs into the patient's regimen with caution. - If syncope occurs, the patient should be placed in the recumbent position and treated supportively as necessary. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration. - Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol. - Patients should always be started on the 1 mg capsules of prazosin. The 2 and 5 mg capsules are not indicated for initial therapy. - More common than loss of consciousness are the symptoms often associated with lowering of the blood pressure, namely: - Dizziness - Lightheadedness. - The patient should be cautioned about these possible adverse effects and advised what measures to take should they develop. The patient should also be cautioned to avoid situations where injury could result should syncope occur during the initiation of prazosin therapy. # Adverse Reactions ## Clinical Trials Experience - Clinical trials were conducted on more than 900 patients. During these trials and subsequent marketing experience, the most frequent reactions associated with prazosin therapy are: - Dizziness 10.3% - Headache 7.8% - Drowsiness 7.6% - Lack of energy 6.9% - Weakness - Palpitations 5.3% - Nausea 4.9%. - In most instances, side effects have disappeared with continued therapy or have been tolerated with no decrease in dose of drug. - Less frequent adverse reactions which are reported to occur in 1–4% of patients are: - Vertigo - Depression - Nervousness - Edema - Orthostatic hypotension - Dyspnea - Syncope - Vomiting - Diarrhea - Constipation - Rash - Urinary frequency - Blurred vision - Reddened sclera - Epistaxis - Dry mouth - Nasal congestion - Fewer than 1% of patients have reported the following: - Abdominal discomfort - Liver function abnormalities - Pancreatitis - Tachycardia - Paresthesia - Hallucinations - Pruritus - Alopecia - Lichen planus - Incontinence - Impotence - Priapism - Tinnitus - Diaphoresis - Fever - Positive ANA titer - Arthralgia - Single reports of pigmentary mottling and serous retinopathy, and a few reports of cataract development or disappearance have been reported. In these instances, the exact causal relationship has not been established because the baseline observations were frequently inadequate. - In more specific slit-lamp and funduscopic studies, which included adequate baseline examinations, no drug-related abnormal ophthalmological findings have been reported. - Literature reports exist associating prazosin therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases. ## Postmarketing Experience - Allergic reaction - Asthenia - Malaise - Pain - Flushing - Angina pectoris - Hypotension - Bradycardia - Gynecomastia - Insomnia - Urticaria - Vasculitis - Eye pain - During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha-1 blocker therapy # Drug Interactions - Prazosin has been administered without any adverse drug interaction in limited clinical experience to date with the following: - Cardiac glycosides: - Digitalis - Digoxin - Hypoglycemics: - Insulin - Chlorpropamide - Phenformin - Tolazamide - Tolbutamide - Tranquilizers and sedatives: - Chlordiazepoxide - Diazepam - Phenobarbital - Antigout - Allopurinol - Colchicine - Probenecid - Antiarrhythmics - Procainamide - Propranolol - Quinidine - Analgesics, antipyretics and anti-inflammatories - Propoxyphene - Aspirin - Indomethacin - Phenylbutazone - Addition of a diuretic or other antihypertensive agent to prazosin has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin based on clinical response. - Concomitant administration of prazosin with a phosphodiesterase-5 inhibitor can result in: - Additive blood pressure lowering effects - Symptomatic hypotension # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): C - Prazosin has been shown to be associated with decreased litter size at birth, 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose, respectively. - The use of prazosin and a beta-blocker for the control of severe hypertension in 44 pregnant women revealed no drug-related fetal abnormalities or adverse effects. Therapy with prazosin was continued for as long as 14 weeks. Prazosin has also been used alone or in combination with other hypotensive agents in severe hypertension of pregnancy by other investigators. No fetal or neonatal abnormalities have been reported with the use of prazosin. - There are no adequate and well controlled studies which establish the safety of prazosin in pregnant women. Prazosin should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. Pregnancy Category (AUS): B2 There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of prazosin in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Prazosin during labor and delivery. ### Nursing Mothers - Prazosin has been shown to be excreted in small amounts in human milk. Caution should be exercised when prazosin is administered to a nursing woman. ### Pediatric Use - Safety and effectiveness in children have not been established. ### Geriatic Use There is no FDA guidance on the use of Prazosin in geriatric settings. ### Gender There is no FDA guidance on the use of Prazosin with respect to specific gender populations. ### Race There is no FDA guidance on the use of Prazosin with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Prazosin in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Prazosin in patients with hepatic impairment. ### Females of Reproductive Potential and Males - No carcinogenic potential was demonstrated in an 18 month study in rats with prazosin at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day. - Prazosin was not mutagenic in in vivo genetic toxicology studies. - In a fertility and general reproductive performance study in rats, both males and females, treated with 75 mg/kg (225 times the usual maximum recommended human dose), demonstrated decreased fertility, while those treated with 25 mg/kg (75 times the usual maximum recommended human dose) did not. - In chronic studies (one year or more) of prazosin in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (75 times the usual maximum recommended human dose). No testicular changes were seen in rats or dogs at 10 mg/kg/day (30 times the usual maximum recommended human dose). In view of the testicular changes observed in animals, 105 patients on long term prazosin therapy were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition, 27 males on prazosin for up to 51 months did not have changes in sperm morphology suggestive of drug effect. ### Immunocompromised Patients There is no FDA guidance one the use of Prazosin in patients who are immunocompromised. # Administration and Monitoring ### Administration Oral ### Monitoring - Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol. # IV Compatibility There is limited information regarding the compatibility of Prazosin and IV administrations. # Overdosage - Accidental ingestion of at least 50 mg of prazosin in a two year old child resulted in: - Profound drowsiness - Depressed reflexes - No decrease in blood pressure was noted. - Recovery was uneventful. ## Acute Overdose ### Hypotension - Should overdosage lead to hypotension, support of the cardiovascular system is of first importance. ### Management - Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. - If this measure is inadequate: - Shock should first be treated with volume expanders. - If necessary, vasopressors should then be used. - Renal function should be monitored and supported as needed. # Pharmacology ## Mechanism of Action - The exact mechanism of the hypotensive action of prazosin is unknown: - Prazosin causes a decrease in total peripheral resistance and was originally thought to have a direct relaxant action on vascular smooth muscle. - Recent animal studies, however, have suggested that the vasodilator effect of prazosin is also related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). - Unlike conventional alpha-blockers, the antihypertensive action of prazosin is usually not accompanied by a reflex tachycardia. Tolerance has not been observed to develop in long term therapy. ## Structure Prazosin, a quinazoline derivative, is the first of a new chemical class of antihypertensives. It is the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl) piperazine and its structural formula is: Molecular formula C19H21N5O4HCl It is a white, crystalline substance, slightly soluble in water and isotonic saline, and has a molecular weight of 419.87. Each 1 mg capsule of prazosin for oral use contains drug equivalent to 1 mg free base. Inert ingredients in the formulations are: hard gelatin capsules (which may contain Blue 1, Red 3, Red 28, Red 40, and other inert ingredients); magnesium stearate; sodium lauryl sulfate; starch; sucrose. ## Pharmacodynamics - Hemodynamic studies have been carried out in man following acute single dose administration and during the course of long term maintenance therapy. - The results confirm that the therapeutic effect is a fall in blood pressure unaccompanied by a clinically significant change in cardiac output, heart rate, renal blood flow and glomerular filtration rate. - There is no measurable negative chronotropic effect. - In clinical studies to date, prazosin hydrochloride has not increased plasma renin activity. - In man, blood pressure is lowered in both the supine and standing positions. This effect is most pronounced on the diastolic blood pressure. - In clinical studies in which lipid profiles were followed, there were generally no adverse changes noted between pre- and post-treatment lipid levels. ## Pharmacokinetics - Following oral administration, human plasma concentrations reach a peak at about three hours with a plasma half-life of two to three hours. The drug is highly bound to plasma protein. Bioavailability studies have demonstrated that the total absorption relative to the drug in a 20% alcoholic solution is 90%, resulting in peak levels approximately 65% of that of the drug in solution. - Animal studies indicate that prazosin hydrochloride is extensively metabolized, primarily by demethylation and conjugation, and excreted mainly via bile and feces. Less extensive human studies suggest similar metabolism and excretion in man. ## Nonclinical Toxicology There is limited information regarding Nonclinical Toxicology of prazosin in the drug label. # Clinical Studies There is limited information regarding Clinical Studies of prazosin in the drug label. # How Supplied ## Storage There is limited information regarding storage conditions of doxazosin in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information Dizziness or drowsiness may occur after the first dose of this medicine. Avoid driving or performing hazardous tasks for the first 24 hours after taking this medicine or when the dose is increased. Dizziness, lightheadedness, or fainting may occur, especially when rising from a lying or sitting position. Getting up slowly may help lessen the problem. These effects may also occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot. While taking MINIPRESS, be careful in the amount of alcohol you drink. Also, use extra care during exercise or hot weather, or if standing for long periods. Check with your physician if you have any questions. # Precautions with Alcohol - Effects such as such as dizziness, lightheadedness, or fainting may occur when taking prazosin, especially when rising from a lying or sitting position: - These effects may also occur in case of alcohol consumption, when standing for long periods of time, exercise, or in presence of hot weather. Attention should be given when taking prazosin, particularly to the amount of alcohol consumed. # Brand Names - Minipress # Look-Alike Drug Names - N/A # Drug Shortage Status Drug Shortage # Price	Prazosin Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [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 Prazosin is a alpha-adrenergic blocker that is FDA approved for the {{{indicationType}}} of hypertension. Common adverse reactions include orthostatic hypotension, palpitations, nausea, asthenia, dizziness, headache, lethargy and somnolence. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Initial dose: - 1 mg two or three times a day - Maintenance dose: - Dosage may be slowly increased to a total daily dose of 20 mg given in divided doses. The therapeutic dosages most commonly employed have ranged from 6 mg to 15 mg daily given in divided doses. Doses higher than 20 mg usually do not increase efficacy, however a few patients may benefit from further increases up to a daily dose of 40 mg given in divided doses. After initial titration some patients can be maintained adequately on a twice daily dosage regimen. - Use with other drugs: - When adding a diuretic or other antihypertensive agent, the dose of prazosin should be reduced to 1 mg or 2 mg three times a day and retitration then carried out. - Concomitant administration of prazosin with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking prazosin. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Prazosin in adult patients. ### Non–Guideline-Supported Use - Prazosin has been used in the treatment benign prostatic hyperplasia.[1] - Prazosin has been successfully used in the hemodynamic management of patients with congestive heart failure.[2] - A 6-week open-label trial, with 5 patients, with history of exposure to civilian trauma, in a non-military environment, who subsequently developed posttraumatic stress disorder (PTSD):[3][4] - 1 to 4 mg/day - An 8-week open-label trial, with 4 patients, with history of combat trauma nightmares and chronic DSM-IV posttraumatic stress disorder (PTSD) with concomitant severe intractable combat trauma nightmares:[5] - 2 to 10 mg/day - The association of alprostadil and prazosin is an effective option for the treatment of erectile dysfunction. - The therapeutic response to prazosin proved to be better than the placebo response for the following dosages of prazosin: - 250, 500, 1000, and 2000 micrograms[6] - A study shows that there is benefit in the use of prazosin in cases of envenomation by the Indian red scorpion, showed by the reduction of morbidity, mortality, and recovery time. - 0.5 mg every 6 hours, until improvement of the clinical status.[7] - According to a double-blind study, Prazosin shows therapeutic benefit when compared to the placebo, for the treatment of Raynaud phenomenon. - 1 mg orally 3 times/day[8] # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding FDA-Label indications Use of Prazosin in pediatric patients. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Prazosin in pediatric patients. ### Non–Guideline-Supported Use - A study shows that there is benefit in the use of prazosin in cases of envenomation by the Indian red scorpion, showed by the reduction of morbidity, mortality, and recovery time. - 0.25 mg every 6 hours, until improvement of the clinical status.[7] # Contraindications - Prazosin is contraindicated in patients with known sensitivity to: - Quinazolines - Prazosin - Any of the inert ingredients # Warnings - Prazosin, as other alpha-blockers, may cause: - Syncope with sudden loss of consciousness: - May be due to an excessive postural hypotensive effect - Occasionally the syncopal episode has been preceded by a bout of severe tachycardia with heart rates of 120–160 beats per minute - Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug - These have often been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of prazosin. - The incidence of syncopal episodes is approximately 1% in patients given an initial dose of 2 mg or greater. - Clinical trials conducted during the investigational phase of this drug suggest that syncopal episodes can be minimized by limiting the initial dose of the drug to 1 mg, by subsequently increasing the dosage slowly, and by introducing any additional antihypertensive drugs into the patient's regimen with caution. - If syncope occurs, the patient should be placed in the recumbent position and treated supportively as necessary. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration. - Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol. - Patients should always be started on the 1 mg capsules of prazosin. The 2 and 5 mg capsules are not indicated for initial therapy. - More common than loss of consciousness are the symptoms often associated with lowering of the blood pressure, namely: - Dizziness - Lightheadedness. - The patient should be cautioned about these possible adverse effects and advised what measures to take should they develop. The patient should also be cautioned to avoid situations where injury could result should syncope occur during the initiation of prazosin therapy. # Adverse Reactions ## Clinical Trials Experience - Clinical trials were conducted on more than 900 patients. During these trials and subsequent marketing experience, the most frequent reactions associated with prazosin therapy are: - Dizziness 10.3% - Headache 7.8% - Drowsiness 7.6% - Lack of energy 6.9% - Weakness - Palpitations 5.3% - Nausea 4.9%. - In most instances, side effects have disappeared with continued therapy or have been tolerated with no decrease in dose of drug. - Less frequent adverse reactions which are reported to occur in 1–4% of patients are: - Vertigo - Depression - Nervousness - Edema - Orthostatic hypotension - Dyspnea - Syncope - Vomiting - Diarrhea - Constipation - Rash - Urinary frequency - Blurred vision - Reddened sclera - Epistaxis - Dry mouth - Nasal congestion - Fewer than 1% of patients have reported the following: - Abdominal discomfort - Liver function abnormalities - Pancreatitis - Tachycardia - Paresthesia - Hallucinations - Pruritus - Alopecia - Lichen planus - Incontinence - Impotence - Priapism - Tinnitus - Diaphoresis - Fever - Positive ANA titer - Arthralgia - Single reports of pigmentary mottling and serous retinopathy, and a few reports of cataract development or disappearance have been reported. In these instances, the exact causal relationship has not been established because the baseline observations were frequently inadequate. - In more specific slit-lamp and funduscopic studies, which included adequate baseline examinations, no drug-related abnormal ophthalmological findings have been reported. - Literature reports exist associating prazosin therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases. ## Postmarketing Experience - Allergic reaction - Asthenia - Malaise - Pain - Flushing - Angina pectoris - Hypotension - Bradycardia - Gynecomastia - Insomnia - Urticaria - Vasculitis - Eye pain - During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha-1 blocker therapy # Drug Interactions - Prazosin has been administered without any adverse drug interaction in limited clinical experience to date with the following: - Cardiac glycosides: - Digitalis - Digoxin - Hypoglycemics: - Insulin - Chlorpropamide - Phenformin - Tolazamide - Tolbutamide - Tranquilizers and sedatives: - Chlordiazepoxide - Diazepam - Phenobarbital - Antigout - Allopurinol - Colchicine - Probenecid - Antiarrhythmics - Procainamide - Propranolol - Quinidine - Analgesics, antipyretics and anti-inflammatories - Propoxyphene - Aspirin - Indomethacin - Phenylbutazone - Addition of a diuretic or other antihypertensive agent to prazosin has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin based on clinical response. - Concomitant administration of prazosin with a phosphodiesterase-5 inhibitor can result in: - Additive blood pressure lowering effects - Symptomatic hypotension # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): C - Prazosin has been shown to be associated with decreased litter size at birth, 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose, respectively. - The use of prazosin and a beta-blocker for the control of severe hypertension in 44 pregnant women revealed no drug-related fetal abnormalities or adverse effects. Therapy with prazosin was continued for as long as 14 weeks. Prazosin has also been used alone or in combination with other hypotensive agents in severe hypertension of pregnancy by other investigators. No fetal or neonatal abnormalities have been reported with the use of prazosin. - There are no adequate and well controlled studies which establish the safety of prazosin in pregnant women. Prazosin should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. Pregnancy Category (AUS): B2 There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of prazosin in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Prazosin during labor and delivery. ### Nursing Mothers - Prazosin has been shown to be excreted in small amounts in human milk. Caution should be exercised when prazosin is administered to a nursing woman. ### Pediatric Use - Safety and effectiveness in children have not been established. ### Geriatic Use There is no FDA guidance on the use of Prazosin in geriatric settings. ### Gender There is no FDA guidance on the use of Prazosin with respect to specific gender populations. ### Race There is no FDA guidance on the use of Prazosin with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Prazosin in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Prazosin in patients with hepatic impairment. ### Females of Reproductive Potential and Males - No carcinogenic potential was demonstrated in an 18 month study in rats with prazosin at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day. - Prazosin was not mutagenic in in vivo genetic toxicology studies. - In a fertility and general reproductive performance study in rats, both males and females, treated with 75 mg/kg (225 times the usual maximum recommended human dose), demonstrated decreased fertility, while those treated with 25 mg/kg (75 times the usual maximum recommended human dose) did not. - In chronic studies (one year or more) of prazosin in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (75 times the usual maximum recommended human dose). No testicular changes were seen in rats or dogs at 10 mg/kg/day (30 times the usual maximum recommended human dose). In view of the testicular changes observed in animals, 105 patients on long term prazosin therapy were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition, 27 males on prazosin for up to 51 months did not have changes in sperm morphology suggestive of drug effect. ### Immunocompromised Patients There is no FDA guidance one the use of Prazosin in patients who are immunocompromised. # Administration and Monitoring ### Administration Oral ### Monitoring - Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol. # IV Compatibility There is limited information regarding the compatibility of Prazosin and IV administrations. # Overdosage - Accidental ingestion of at least 50 mg of prazosin in a two year old child resulted in: - Profound drowsiness - Depressed reflexes - No decrease in blood pressure was noted. - Recovery was uneventful. ## Acute Overdose ### Hypotension - Should overdosage lead to hypotension, support of the cardiovascular system is of first importance. ### Management - Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. - If this measure is inadequate: - Shock should first be treated with volume expanders. - If necessary, vasopressors should then be used. - Renal function should be monitored and supported as needed. # Pharmacology ## Mechanism of Action - The exact mechanism of the hypotensive action of prazosin is unknown: - Prazosin causes a decrease in total peripheral resistance and was originally thought to have a direct relaxant action on vascular smooth muscle. - Recent animal studies, however, have suggested that the vasodilator effect of prazosin is also related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). - Unlike conventional alpha-blockers, the antihypertensive action of prazosin is usually not accompanied by a reflex tachycardia. Tolerance has not been observed to develop in long term therapy. ## Structure Prazosin, a quinazoline derivative, is the first of a new chemical class of antihypertensives. It is the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl) piperazine and its structural formula is: Molecular formula C19H21N5O4•HCl It is a white, crystalline substance, slightly soluble in water and isotonic saline, and has a molecular weight of 419.87. Each 1 mg capsule of prazosin for oral use contains drug equivalent to 1 mg free base. Inert ingredients in the formulations are: hard gelatin capsules (which may contain Blue 1, Red 3, Red 28, Red 40, and other inert ingredients); magnesium stearate; sodium lauryl sulfate; starch; sucrose. ## Pharmacodynamics - Hemodynamic studies have been carried out in man following acute single dose administration and during the course of long term maintenance therapy. - The results confirm that the therapeutic effect is a fall in blood pressure unaccompanied by a clinically significant change in cardiac output, heart rate, renal blood flow and glomerular filtration rate. - There is no measurable negative chronotropic effect. - In clinical studies to date, prazosin hydrochloride has not increased plasma renin activity. - In man, blood pressure is lowered in both the supine and standing positions. This effect is most pronounced on the diastolic blood pressure. - In clinical studies in which lipid profiles were followed, there were generally no adverse changes noted between pre- and post-treatment lipid levels. ## Pharmacokinetics - Following oral administration, human plasma concentrations reach a peak at about three hours with a plasma half-life of two to three hours. The drug is highly bound to plasma protein. Bioavailability studies have demonstrated that the total absorption relative to the drug in a 20% alcoholic solution is 90%, resulting in peak levels approximately 65% of that of the drug in solution. - Animal studies indicate that prazosin hydrochloride is extensively metabolized, primarily by demethylation and conjugation, and excreted mainly via bile and feces. Less extensive human studies suggest similar metabolism and excretion in man. ## Nonclinical Toxicology There is limited information regarding Nonclinical Toxicology of prazosin in the drug label. # Clinical Studies There is limited information regarding Clinical Studies of prazosin in the drug label. # How Supplied ## Storage There is limited information regarding storage conditions of doxazosin in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information Dizziness or drowsiness may occur after the first dose of this medicine. Avoid driving or performing hazardous tasks for the first 24 hours after taking this medicine or when the dose is increased. Dizziness, lightheadedness, or fainting may occur, especially when rising from a lying or sitting position. Getting up slowly may help lessen the problem. These effects may also occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot. While taking MINIPRESS, be careful in the amount of alcohol you drink. Also, use extra care during exercise or hot weather, or if standing for long periods. Check with your physician if you have any questions. # Precautions with Alcohol - Effects such as such as dizziness, lightheadedness, or fainting may occur when taking prazosin, especially when rising from a lying or sitting position: - These effects may also occur in case of alcohol consumption, when standing for long periods of time, exercise, or in presence of hot weather. Attention should be given when taking prazosin, particularly to the amount of alcohol consumed. # Brand Names - Minipress # Look-Alike Drug Names - N/A # Drug Shortage Status Drug Shortage # Price	https://www.wikidoc.org/index.php/Minipress
501b13cc228722669b31d6e2d08bfc0f14f7f686	wikidoc	Mnemonic	Mnemonic # Overview A mnemonic (pronounced Template:IPAEng in RP, Template:IPA in GA) is a memory aid that generally serves an educational purpose. They are mostly verbal, e.g a word, each of whose letters help the user to remember the first letters of items in a list. However, there are also other types of mnemonics, such as visual mnemonics. Mnemonics rely on associations between something that is easy to remember, and something that is harder to remember. Sometimes mnemonics are chosen to directly relate to the target information, and othertimes they are arbitrary. The word mnemonic is derived from the Ancient Greek word μνημονικός mnemonikos ("of memory") and is related to Mnemosyne ("remembrance"), the name of the Mother of the Muses in Greek mythology. Both of these words refer back to μνημα mnema ("remembrance"). The first known reference to mnemonics is the method of loci described in Cicero's De Oratore. # Mnemonic systems ## Key-word mnemonics Visual mnemonics are very popular in medicine as well as other fields. In this technique, an image portrays characters or objects whose name sounds like the item that has to be memorized. This object then interacts with other similarly portrayed objects that in turn represent associated information. Mnemonic techniques can also be strategies for encoding information so that recall is easier. A good example of medical visual mnemonics Mediglyphics Pharmacology ## Acronym and acrostic mnemonics One common mnemonic for remembering lists consists of an easily remembered word, phrase, or rhyme whose first letters are associated with the list items. The idea lends itself well to memorizing hard-to-break passwords as well. Though easy to derive, they are often not as powerful as the classical systems because they do not make use of visualization techniques. ## Anamonics (Scrabble) Many tournament Scrabble players employ anamonics, a form of initialization mnemonic, for the purposes of learning and quickly recalling sets of acceptable words. An anamonic consists of a "stem" (usually of six or seven letters), paired with a semantically related phrase, in which each letter of the phrase can be added to the stem and rearranged to form at least one acceptable word. For example, if a player has the tiles "ACDEIRT" on his rack, and recalls the anamonic "DICE-ART = casino math diploma", they will know precisely which letters may be played through to form 8-letter words, and will hopefully be aided in finding the words: "ACCREDIT", "RADICATE", "ACRIDEST", "RATICIDE", "DICENTRA", "CERATOID", "TIMECARD", "CITRATED"/ "TETRACID"/ "TETRADIC", "TRACHEID", "READDICT", "PICRATED", and "ARTICLED"/ "LACERTID". ## Other mnemonic systems - Mnemonic major system - Mnemonic dominic system - Mnemonic link system\|Link System - Mnemonic peg system - Mnemonic goroawase system\|Goroawase System - Mnemonic journey method\|Journey method - Method of loci - Latin mnemonics\|Mnemonics for Latin study # Arbitrariness of mnemonics A curious characteristic of many memory systems is that mnemonics work despite being (or possibly because of being) illogical, arbitrary, and artistically flawed. A commonly effective mnemonic for remembering the color sequence in a rainbow, "Roy G. Biv", is a combination of such unlikely elements: "Roy" is a legitimate first name, but there is no actual surname "Biv" and of course the middle initial "G" is arbitrary. Medical students never forget the arbitrary nationalities of the Finn and German. Any two of the three months ending in -ember would fit just as euphoniously as September and November in "Thirty days hath...", yet most people can remember the rhyme correctly for a lifetime after having heard it once, and are never troubled by doubts as to which two of the -ember months have thirty days. Associations which are exaggerated, absurd, humorous or have sexual connotation are easier to remember than normal ones. One reason for the effectiveness of seemingly arbitrary mnemonics is the grouping of information to reduce cognitive load. Just as US phone numbers chunks 10 digits into three groups, the name "Roy G. Biv" chunks seven colors into two short names and an initial. Various studies (most notably Miller's The Magical Number Seven, Plus or Minus Two) have shown that the human brain is capable of remembering only a limited number of arbitrary items; chunking these items permits the brain to hold more of them in memory. # Assembly mnemonics In assembly language a mnemonic is a code, usually from 1 to 5 letters, that represents an opcode, a number. Programming in machine code, by supplying the computer with the numbers of the operations it must perform, can be quite a burden, because for every operation the corresponding number must be looked up or remembered. Looking up all numbers takes a lot of time, and mis-remembering a number may introduce computer bugs. Therefore a set of mnemonics was devised. Each number was represented by an alphabetic code. So instead of entering the number corresponding to addition to add two numbers one can enter "add". Although mnemonics differ between different CPU designs some are common, for instance: "sub" (subtract), "div" (divide), "add" (add) and "mul" (multiply). This type of mnemonic is different from the ones listed above in that instead of a way to make remembering numbers easier, it is a way to make remembering numbers unnecessary (by relying on some external way to tie each mnemonic to a number). # Los Angeles, California, Downtown Streets Mnemonic Central downtown Los Angeles can be a confusing maze, both for "suburbians" and tourists alike. Moving from North to South (actually NE to SW), it's fairly easy to go from the 101 (Hollywood/Santa Ana) Freeway to Temple Street, followed by Tom Bradley Blvd. (previously 1st Street), then 2nd Street, 3rd Street, etc. However, East to West (actually SE to NW) is a bit more challenging to navigate. At some point, someone introduced a mnemonic sentence to recall the order of the 10 primary East to West streets. This version is courtesy of St. Louis, Missouri, native Helen Anshutz Meixsell, who began her residency in Los Angeles in 1927 at the age of nine. It was taught to her by her aunt, MayBelle Anshutz, who had been in California since 1926. After Ms. Meixsell's graduation from Los Angeles High School in 1936, and until 1942, she worked at various jobs from downtown Los Angeles to her non-enlisted WWII military job at Douglas Aircraft across town in Santa Monica. Although slight variations can undoubtedly be found, Ms. Meixsell memorized it this way in 1935 in anticipation of traveling to work: In LOS ANGELES, you MAINly SPRING onto BROADWAY, go up the HILL to OLIVE with the GRAND HOPE of picking FLOWERs on FIGUEROA. (All roads mentioned in the saying are "streets" except for Grand, which is an "avenue".) She utilized the expression every day as she regularly walked, took city buses and rode the “Red Car” to her jobs. # UK Fuel Mnemonics All UK petrol (gasoline) stations use a Mnemonic code to identify themselves. This remains the same no matter how many times the service station changes hands. These are made up of seven letters. The first three letters are the site name. The next set of three are the name of the town the site is located in or near. The seventh letter is always an R. For example, a site named Rock in Stamford, Lincolnshire\|Stamford has the mnemonic ROCSTAR. Occasionally an extra letter is added if there are, or once were, two sites with the same name on either side of a motorway or trunk road. As the sites are usually appended South or North, depending on which side of the road they are, this letter is added either between the 3rd and 4th letter or before the final R. So a site called Orsett North near Ockendon becomes ORSNOCKR or ORSOCKNR, and Orsett South is ORSSOCKR or ORSOCKSR.	Mnemonic # Overview A mnemonic (pronounced Template:IPAEng in RP, Template:IPA in GA) is a memory aid that generally serves an educational purpose. They are mostly verbal, e.g a word, each of whose letters help the user to remember the first letters of items in a list. However, there are also other types of mnemonics, such as visual mnemonics. Mnemonics rely on associations between something that is easy to remember, and something that is harder to remember. Sometimes mnemonics are chosen to directly relate to the target information, and othertimes they are arbitrary. The word mnemonic is derived from the Ancient Greek word μνημονικός mnemonikos ("of memory") and is related to Mnemosyne ("remembrance"), the name of the Mother of the Muses in Greek mythology. Both of these words refer back to μνημα mnema ("remembrance").[1] The first known reference to mnemonics is the method of loci described in Cicero's De Oratore. # Mnemonic systems ## Key-word mnemonics Visual mnemonics are very popular in medicine as well as other fields. In this technique, an image portrays characters or objects whose name sounds like the item that has to be memorized. This object then interacts with other similarly portrayed objects that in turn represent associated information. Mnemonic techniques can also be strategies for encoding information so that recall is easier. A good example of medical visual mnemonics Mediglyphics Pharmacology ## Acronym and acrostic mnemonics One common mnemonic for remembering lists consists of an easily remembered word, phrase, or rhyme whose first letters are associated with the list items. The idea lends itself well to memorizing hard-to-break passwords as well. Though easy to derive, they are often not as powerful as the classical systems because they do not make use of visualization techniques. ## Anamonics (Scrabble) Many tournament Scrabble players employ anamonics, a form of initialization mnemonic, for the purposes of learning and quickly recalling sets of acceptable words. An anamonic consists of a "stem" (usually of six or seven letters), paired with a semantically related phrase, in which each letter of the phrase can be added to the stem and rearranged to form at least one acceptable word. For example, if a player has the tiles "ACDEIRT" on his rack, and recalls the anamonic "DICE-ART = casino math diploma", they will know precisely which letters may be played through to form 8-letter words, and will hopefully be aided in finding the words: "ACCREDIT", "RADICATE", "ACRIDEST", "RATICIDE", "DICENTRA", "CERATOID", "TIMECARD", "CITRATED"/ "TETRACID"/ "TETRADIC", "TRACHEID", "READDICT", "PICRATED", and "ARTICLED"/ "LACERTID". ## Other mnemonic systems - Mnemonic major system - Mnemonic dominic system - Mnemonic link system\|Link System - Mnemonic peg system - Mnemonic goroawase system\|Goroawase System - Mnemonic journey method\|Journey method - Method of loci - Latin mnemonics\|Mnemonics for Latin study # Arbitrariness of mnemonics A curious characteristic of many memory systems is that mnemonics work despite being (or possibly because of being) illogical, arbitrary, and artistically flawed. A commonly effective mnemonic for remembering the color sequence in a rainbow, "Roy G. Biv", is a combination of such unlikely elements: "Roy" is a legitimate first name, but there is no actual surname "Biv" and of course the middle initial "G" is arbitrary. Medical students never forget the arbitrary nationalities of the Finn and German. Any two of the three months ending in -ember would fit just as euphoniously as September and November in "Thirty days hath...", yet most people can remember the rhyme correctly for a lifetime after having heard it once, and are never troubled by doubts as to which two of the -ember months have thirty days. Associations which are exaggerated, absurd, humorous or have sexual connotation are easier to remember than normal ones. [2] One reason for the effectiveness of seemingly arbitrary mnemonics is the grouping of information to reduce cognitive load. Just as US phone numbers chunks 10 digits into three groups, the name "Roy G. Biv" chunks seven colors into two short names and an initial. Various studies (most notably Miller's The Magical Number Seven, Plus or Minus Two) have shown that the human brain is capable of remembering only a limited number of arbitrary items; chunking these items permits the brain to hold more of them in memory. # Assembly mnemonics In assembly language a mnemonic is a code, usually from 1 to 5 letters, that represents an opcode, a number. Programming in machine code, by supplying the computer with the numbers of the operations it must perform, can be quite a burden, because for every operation the corresponding number must be looked up or remembered. Looking up all numbers takes a lot of time, and mis-remembering a number may introduce computer bugs. Therefore a set of mnemonics was devised. Each number was represented by an alphabetic code. So instead of entering the number corresponding to addition to add two numbers one can enter "add". Although mnemonics differ between different CPU designs some are common, for instance: "sub" (subtract), "div" (divide), "add" (add) and "mul" (multiply). This type of mnemonic is different from the ones listed above in that instead of a way to make remembering numbers easier, it is a way to make remembering numbers unnecessary (by relying on some external way to tie each mnemonic to a number). # Los Angeles, California, Downtown Streets Mnemonic Central downtown Los Angeles can be a confusing maze, both for "suburbians" and tourists alike. Moving from North to South (actually NE to SW), it's fairly easy to go from the 101 (Hollywood/Santa Ana) Freeway to Temple Street, followed by Tom Bradley Blvd. (previously 1st Street), then 2nd Street, 3rd Street, etc. However, East to West (actually SE to NW) is a bit more challenging to navigate. At some point, someone introduced a mnemonic sentence to recall the order of the 10 primary East to West streets. This version is courtesy of St. Louis, Missouri, native Helen Anshutz Meixsell, who began her residency in Los Angeles in 1927 at the age of nine. It was taught to her by her aunt, MayBelle Anshutz, who had been in California since 1926. After Ms. Meixsell's graduation from Los Angeles High School in 1936, and until 1942, she worked at various jobs from downtown Los Angeles to her non-enlisted WWII military job at Douglas Aircraft across town in Santa Monica. Although slight variations can undoubtedly be found, Ms. Meixsell memorized it this way in 1935 in anticipation of traveling to work: In LOS ANGELES, you MAINly SPRING onto BROADWAY, go up the HILL to OLIVE with the GRAND HOPE of picking FLOWERs on FIGUEROA. (All roads mentioned in the saying are "streets" except for Grand, which is an "avenue".) She utilized the expression every day as she regularly walked, took city buses and rode the “Red Car” to her jobs. # UK Fuel Mnemonics All UK petrol (gasoline) stations use a Mnemonic code to identify themselves. This remains the same no matter how many times the service station changes hands. These are made up of seven letters. The first three letters are the site name. The next set of three are the name of the town the site is located in or near. The seventh letter is always an R. For example, a site named Rock in Stamford, Lincolnshire\|Stamford has the mnemonic ROCSTAR. Occasionally an extra letter is added if there are, or once were, two sites with the same name on either side of a motorway or trunk road. As the sites are usually appended South or North, depending on which side of the road they are, this letter is added either between the 3rd and 4th letter or before the final R. So a site called Orsett North near Ockendon becomes ORSNOCKR or ORSOCKNR, and Orsett South is ORSSOCKR or ORSOCKSR.	https://www.wikidoc.org/index.php/Mnemonic
d8466b5744fbf9a7f8b3dc68c8e94e83cde52bb3	wikidoc	Molecule	Molecule In chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two atoms in a definite arrangement held together by strong chemical bonds. In organic chemistry and biochemistry, the term molecule is used less strictly and also is applied to charged organic molecules and biomolecules. Molecules are distinguished from polyatomic ions in the strict sense. This definition has evolved as knowledge of the structure of molecules has increased. Earlier definitions were less precise defining molecules as the smallest particles of pure chemical substances that still retain their composition and chemical properties. This definition often breaks down since many substances in ordinary experience, such as rocks, salts, and metals, are composed of atoms or ions, but are not made of molecules. In the kinetic theory of gases the term molecule is often used for any gaseous particle regardless of their composition. According to this definition noble gases would also be considered molecules despite the fact that they are composed of a single non-bonded atom. # History The term "molecule", from the French molécule meaning "extremely minute particle," was coined by French philosopher Rene Descartes in the 1620s. Although the existence of molecules was accepted by many chemists since the early 19th century as a result of Dalton's laws of Definite and Multiple Proportions (1803-1808) and Avogadro's law (1811), there was some resistance among positivists and physicists such as Mach, Boltzmann, Maxwell, and Gibbs, who saw molecules merely as convenient mathematical constructs. The work of Perrin on Brownian motion (1911) is considered to be the final proof of the existence of molecules. In a molecule, at least two atoms are joined by shared pairs of electrons in a covalent bond. It may consist of atoms of the same chemical element, as with oxygen (O2), or of different elements, as with water (H2O). Atoms and complexes connected by non-covalent bonds such as hydrogen bonds or ionic bonds are generally not considered single molecules. No typical molecule can be defined for ionic (salts) and covalent crystals (network solids) which are composed of repeating unit cells that extend either in a plane (such as in graphite) or three-dimensionally (such as in diamond or sodium chloride). The science of molecules is called molecular chemistry or molecular physics, depending on the focus. Molecular chemistry deals with the laws governing the interaction between molecules that results in the formation and breakage of chemical bonds, while molecular physics deals with the laws governing their structure and properties. In practice, however, this distinction is vague. In molecular sciences, a molecule consists of a stable system (bound state) comprising two or more atoms. Polyatomic ions may sometimes be usefully thought of as electrically charged molecules. The term unstable molecule is used for very reactive species, i.e., short-lived assemblies (resonances) of electrons and nuclei, such as radicals, molecular ions, Rydberg molecules, transition states, van der Waals complexes, or systems of colliding atoms as in Bose-Einstein condensates. # Molecular size Most molecules are far too small to be seen with the naked eye, but there are exceptions. DNA, a macromolecule, can reach macroscopic sizes, as can molecules of many polymers. The smallest molecule is the diatomic hydrogen (H2), with an overall length of roughly twice the 74 picometres (0.74 Å) bond length. Molecules commonly used as building blocks for organic synthesis have a dimension of a few Å to several dozen Å. Single molecules cannot usually be observed by light (as noted above), but small molecules and even the outlines of individual atoms may be traced in some circumstances by use of an atomic force microscope. Some of the largest molecules are macromolecules or supermolecules. # Molecular formula The empirical formula of a molecule is the simplest integer ratio of the chemical elements that constitute the compound. For example, in their pure forms, water is always composed of a 2:1 ratio of hydrogen to oxygen, and ethyl alcohol or ethanol is always composed of carbon, hydrogen, and oxygen in a 2:6:1 ratio. However, this does not determine the kind of molecule uniquely - dimethyl ether has the same ratio as ethanol, for instance. Molecules with the same atoms in different arrangements are called isomers. The empirical formula is often the same as the molecular formula but not always. For example the molecule acetylene has molecular formula C2H2, but the simplest integer ratio of elements is CH. The molecular formula reflects the exact number of atoms that compose a molecule. The molecular mass can be calculated from the chemical formula and is expressed in conventional atomic mass units equal to 1/12th of the mass of a neutral carbon-12 (12C isotope) atom. For network solids, the term formula unit is used in stoichiometric calculations. # Molecular geometry Molecules have fixed equilibrium geometries—bond lengths and angles— about which they continuously oscillate through vibrational and rotational motions. A pure substance is composed of molecules with the same average geometrical structure. The chemical formula and the structure of a molecule are the two important factors that determine its properties, particularly its reactivity. Isomers share a chemical formula but normally have very different properties because of their different structures. Stereoisomers, a particular type of isomers, may have very similar physico-chemical properties and at the same time very different biochemical activities. # Molecular Theory There are four statements of facts concerning molecules. These facts are: 1. All matter are composed of tiny particles called molecules. 2. There are spaces between molecules. 3. Molecules are constantly moving. 4. Molecules attract one another. These statements together form the Molecular Theory. # Molecular spectroscopy Molecular spectroscopy deals with the response (spectrum) of molecules interacting with probing signals of known energy (or frequency, according to Planck's formula). Scattering theory provides the theoretical background for spectroscopy. The probing signal used in spectroscopy can be an electromagnetic wave or a beam of particles (electrons, positrons, etc.) The molecular response can consist of signal absorption (absorption spectroscopy), the emission of another signal (emission spectroscopy), fragmentation, or chemical changes. Spectroscopy is recognized as a powerful tool in investigating the microscopic properties of molecules, in particular their energy levels. In order to extract maximum microscopic information from experimental results, spectroscopy is often coupled with chemical computations. # Theoretical aspects The study of molecules by molecular physics and theoretical chemistry is largely based on quantum mechanics and is essential for the understanding of the chemical bond. The simplest of molecules is the hydrogen molecule-ion, H2+, and the simplest of all the chemical bonds is the one-electron bond. H2+ is composed of two positively-charged protons and one negatively-charged electron bound by photon exchange, which means that the Schrödinger equation for the system can be solved more easily due to the lack of electron–electron repulsion. With the development of fast digital computers, approximate solutions for more complicated molecules became possible and are one of the main aspects of computational chemistry. When trying to define rigorously whether an arrangement of atoms is "sufficiently stable" to be considered a molecule, IUPAC suggests that it "must correspond to a depression on the potential energy surface that is deep enough to confine at least one vibrational state". This definition does not depend on the nature of the interaction between the atoms, but only on the strength of the interaction. In fact, it includes weakly-bound species that would not traditionally be considered molecules, such as the helium dimer, He2, which has one vibrational bound state but is so loosely bound that it is only likely to be observed at very low temperatures.	Molecule Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] In chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two atoms in a definite arrangement held together by strong chemical bonds.[1][2] In organic chemistry and biochemistry, the term molecule is used less strictly and also is applied to charged organic molecules and biomolecules. Molecules are distinguished from polyatomic ions in the strict sense. This definition has evolved as knowledge of the structure of molecules has increased. Earlier definitions were less precise defining molecules as the smallest particles of pure chemical substances that still retain their composition and chemical properties.[3] This definition often breaks down since many substances in ordinary experience, such as rocks, salts, and metals, are composed of atoms or ions, but are not made of molecules. In the kinetic theory of gases the term molecule is often used for any gaseous particle regardless of their composition.[4] According to this definition noble gases would also be considered molecules despite the fact that they are composed of a single non-bonded atom. # History The term "molecule", from the French molécule meaning "extremely minute particle," was coined by French philosopher Rene Descartes in the 1620s. Although the existence of molecules was accepted by many chemists since the early 19th century as a result of Dalton's laws of Definite and Multiple Proportions (1803-1808) and Avogadro's law (1811), there was some resistance among positivists and physicists such as Mach, Boltzmann, Maxwell, and Gibbs, who saw molecules merely as convenient mathematical constructs. The work of Perrin on Brownian motion (1911) is considered to be the final proof of the existence of molecules. In a molecule, at least two atoms are joined by shared pairs of electrons in a covalent bond. It may consist of atoms of the same chemical element, as with oxygen (O2), or of different elements, as with water (H2O). Atoms and complexes connected by non-covalent bonds such as hydrogen bonds or ionic bonds are generally not considered single molecules. No typical molecule can be defined for ionic (salts) and covalent crystals (network solids) which are composed of repeating unit cells that extend either in a plane (such as in graphite) or three-dimensionally (such as in diamond or sodium chloride). The science of molecules is called molecular chemistry or molecular physics, depending on the focus. Molecular chemistry deals with the laws governing the interaction between molecules that results in the formation and breakage of chemical bonds, while molecular physics deals with the laws governing their structure and properties. In practice, however, this distinction is vague. In molecular sciences, a molecule consists of a stable system (bound state) comprising two or more atoms. Polyatomic ions may sometimes be usefully thought of as electrically charged molecules. The term unstable molecule is used for very reactive species, i.e., short-lived assemblies (resonances) of electrons and nuclei, such as radicals, molecular ions, Rydberg molecules, transition states, van der Waals complexes, or systems of colliding atoms as in Bose-Einstein condensates. # Molecular size Most molecules are far too small to be seen with the naked eye, but there are exceptions. DNA, a macromolecule, can reach macroscopic sizes, as can molecules of many polymers. The smallest molecule is the diatomic hydrogen (H2), with an overall length of roughly twice the 74 picometres (0.74 Å) bond length. Molecules commonly used as building blocks for organic synthesis have a dimension of a few Å to several dozen Å. Single molecules cannot usually be observed by light (as noted above), but small molecules and even the outlines of individual atoms may be traced in some circumstances by use of an atomic force microscope. Some of the largest molecules are macromolecules or supermolecules. # Molecular formula The empirical formula of a molecule is the simplest integer ratio of the chemical elements that constitute the compound. For example, in their pure forms, water is always composed of a 2:1 ratio of hydrogen to oxygen, and ethyl alcohol or ethanol is always composed of carbon, hydrogen, and oxygen in a 2:6:1 ratio. However, this does not determine the kind of molecule uniquely - dimethyl ether has the same ratio as ethanol, for instance. Molecules with the same atoms in different arrangements are called isomers. The empirical formula is often the same as the molecular formula but not always. For example the molecule acetylene has molecular formula C2H2, but the simplest integer ratio of elements is CH. The molecular formula reflects the exact number of atoms that compose a molecule. The molecular mass can be calculated from the chemical formula and is expressed in conventional atomic mass units equal to 1/12th of the mass of a neutral carbon-12 (12C isotope) atom. For network solids, the term formula unit is used in stoichiometric calculations. # Molecular geometry Molecules have fixed equilibrium geometries—bond lengths and angles— about which they continuously oscillate through vibrational and rotational motions. A pure substance is composed of molecules with the same average geometrical structure. The chemical formula and the structure of a molecule are the two important factors that determine its properties, particularly its reactivity. Isomers share a chemical formula but normally have very different properties because of their different structures. Stereoisomers, a particular type of isomers, may have very similar physico-chemical properties and at the same time very different biochemical activities. # Molecular Theory There are four statements of facts concerning molecules. These facts are: 1. All matter are composed of tiny particles called molecules. 2. There are spaces between molecules. 3. Molecules are constantly moving. 4. Molecules attract one another. These statements together form the Molecular Theory. # Molecular spectroscopy Molecular spectroscopy deals with the response (spectrum) of molecules interacting with probing signals of known energy (or frequency, according to Planck's formula). Scattering theory provides the theoretical background for spectroscopy. The probing signal used in spectroscopy can be an electromagnetic wave or a beam of particles (electrons, positrons, etc.) The molecular response can consist of signal absorption (absorption spectroscopy), the emission of another signal (emission spectroscopy), fragmentation, or chemical changes. Spectroscopy is recognized as a powerful tool in investigating the microscopic properties of molecules, in particular their energy levels. In order to extract maximum microscopic information from experimental results, spectroscopy is often coupled with chemical computations. # Theoretical aspects The study of molecules by molecular physics and theoretical chemistry is largely based on quantum mechanics and is essential for the understanding of the chemical bond. The simplest of molecules is the hydrogen molecule-ion, H2+, and the simplest of all the chemical bonds is the one-electron bond. H2+ is composed of two positively-charged protons and one negatively-charged electron bound by photon exchange, which means that the Schrödinger equation for the system can be solved more easily due to the lack of electron–electron repulsion. With the development of fast digital computers, approximate solutions for more complicated molecules became possible and are one of the main aspects of computational chemistry. When trying to define rigorously whether an arrangement of atoms is "sufficiently stable" to be considered a molecule, IUPAC suggests that it "must correspond to a depression on the potential energy surface that is deep enough to confine at least one vibrational state".[1] This definition does not depend on the nature of the interaction between the atoms, but only on the strength of the interaction. In fact, it includes weakly-bound species that would not traditionally be considered molecules, such as the helium dimer, He2, which has one vibrational bound state but is so loosely bound that it is only likely to be observed at very low temperatures.	https://www.wikidoc.org/index.php/Molecular
0042356ac171c9ba7aefdd4b2e6f3cf22b1dd0f6	wikidoc	Monensin	Monensin Monensin isolated from Streptomyces cinnamonensis is a well-known representative of naturally polyether ionophore antibiotics . It is able to form pseudomacrocyclic complexes with mono and divalent cations and transport of the cations across cellular membrane. In cells monensin blocks the secretion of glycoproteins. It is soluble in chloroform, ethanol and methanol. Monensin plays an important role as an Na+/H+ antiporter, it blocks intracellular protein transport, and exhibits antibiotic, antimalarial, and other biological activities. The antibacterial properties of monensin and its derivatives are a result of their ability to transport monovalent and divalent metal cations through cellular and subcellular membranes. # Bibliography - A. Agtarap, J.W. Chamberlin, M. Pinkerton, I. Steinrauf, J. Am. Chem. Soc. 89 (1967) 5737. - J.W. Westley, Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York, 1 (1982) 1. - J.W. Westley, Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York, 2 (1983) 51 - B.C. Pressman, Antibiotics and their complexes, Marcel Dekker Inc., New York, (1985) 1. - B.C. Pressman, Annu. Rev. Biochem. 45 (1976) 925. - A. Huczyński, P. Przybylski, B. Brzezinski, F. Bartl, J. Phys. Chem. B 110 (2006) 15615. - M. D. Ruff, in: Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York( 1982,)1,304. - M. W. Osborne, J. Wenger, F. Kovzelove, R. Boyd, M. Zanko, in: Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York (1982) 333. - A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski J. Mol. Struct. 832 (2007) 84-89. - R. Ferdani, G. W. Gokel, in: Encyclopedia of Supramolecular Chemistry: Ionophores, Marcel Dekker Inc. (2004) 760. Cell biology	Monensin Monensin isolated from Streptomyces cinnamonensis is a well-known representative of naturally polyether ionophore antibiotics . It is able to form pseudomacrocyclic complexes with mono and divalent cations and transport of the cations across cellular membrane. In cells monensin blocks the secretion of glycoproteins. It is soluble in chloroform, ethanol and methanol. Monensin plays an important role as an Na+/H+ antiporter, it blocks intracellular protein transport, and exhibits antibiotic, antimalarial, and other biological activities. The antibacterial properties of monensin and its derivatives are a result of their ability to transport monovalent and divalent metal cations through cellular and subcellular membranes. # Bibliography - A. Agtarap, J.W. Chamberlin, M. Pinkerton, I. Steinrauf, J. Am. Chem. Soc. 89 (1967) 5737. - J.W. Westley, Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York, 1 (1982) 1. - J.W. Westley, Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York, 2 (1983) 51 - B.C. Pressman, Antibiotics and their complexes, Marcel Dekker Inc., New York, (1985) 1. - B.C. Pressman, Annu. Rev. Biochem. 45 (1976) 925. - A. Huczyński, P. Przybylski, B. Brzezinski, F. Bartl, J. Phys. Chem. B 110 (2006) 15615. - M. D. Ruff, in: Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York( 1982,)1,304. - M. W. Osborne, J. Wenger, F. Kovzelove, R. Boyd, M. Zanko, in: Polyether Antibiotics. Naturally Occurring Acid Ionophores, Marcel Dekker Inc., New York (1982) 333. - A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski J. Mol. Struct. 832 (2007) 84-89. - R. Ferdani, G. W. Gokel, in: Encyclopedia of Supramolecular Chemistry: Ionophores, Marcel Dekker Inc. (2004) 760. Cell biology Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Monensin
b839f9e47466f586296f26a2e2f4f3b6f0315ed2	wikidoc	Monerans	Monerans Monera are bacteria and other mostly tiny, single-celled organisms whose genetic material is loose in the cell. The genetic material of plants, animals, and other eukaryotes (true nucleus), on the other hand, is held in the cell's nucleus. While the Monera were briefly understood to be one of five biological kingdoms, it is now understood to comprise two domains: the bacteria and the archaea. The Monera kingdom included most organisms with a prokaryotic cell organization (that is, no nucleus). For this reason, the kingdom was sometimes called Prokaryota or Prokaryotae. Recent DNA and RNA sequence analyses has demonstrated that there are two major groups of prokaryotes, the Bacteria and Archaea, which do not appear to be closer in relationship to each other than they are to the Eukaryotes. Thus, Monera has since been divided into Archaea and Bacteria, forming the more recent six-kingdom system and three-domain system. All new schemes abandon the Monera and now treat the Bacteria, Archaea, and Eukarya as separate domains or kingdoms. Prior to the five-kingdom model with its Monera kingdom, these organisms were classifies as two separate divisions of plants: the Schizomycetes (bacteria) were considered fungi, and the Cyanophyta were considered blue-green algae. The latter are now considered a group of bacteria, typically called the cyanobacteria and are now known not to be closely related to plants, fungi, or animals. # Further Classification Based on molecular phylogeny studies, Carl Woese proposed that the prokaryotes (monerans) be divided into two separate groups: Bacteria and Archaea. In Carl Woese's 1990 proposed phylogeny, these three kingdoms are all rooted in a universal common ancestor and this is the most widely accepted categorical phylogeny accepted today. However, the most modern interpretation for these three kingdoms is the "Universal and Eukaryote Phylogenetic Tree" based on 16s rDNA, as presented in the Tree of Life Web Project. ## Bacteria and Archaea Eubacteria and Archaebacteria differ most noticeably in the environments they are able to inhabit. Eubacteria encompass the vast majority of bacteria that come into contact with humans. The bacteria that live within and around humans, such as Escherichia coli and those of the genus Salmonella, are Eubacteria. Archaebacteria live in much harsher conditions, such as in acidic hot springs and at depths of a mile below the arctic ice. These groups were later renamed to Bacteria and Archaea, which might lead to some confusing situations, as the common use of the word "bacteria" in the English language (originally) simply refers to prokaryote microorganisms, or in other words monerans. # History - Traditionally organisms were classified as animal, vegetable, or mineral as in Systema Naturae. After the discovery of microscopy, attempts were made to fit microscopic organisms into either the plant or animal kingdom. In 1866 Ernst Haeckel proposed a three kingdom system which added Protista as a new kingdom that contained most microscopic organisms. One of his eight major divisions of Protista was called Moneres. Haeckel's Moneres subcategory included known bacterial groups such as Vibrio. Haeckel's Protista kingdom also included eukaryotic organisms now classified as Protist. It was later decided that Haeckel's Protista kingdom had proven to be too diverse to be seriously considered one single kingdom. - In 1969, Robert Whittaker published a proposed five kingdom system for classification of living organisms. Whittaker's system placed most single celled organisms into either the prokaryotic Monera or the eukaryotic Protista. The other three kingdoms in his system were the eukaryotic Fungi, Animalia, and Plantae. # Summary	Monerans Monera are bacteria and other mostly tiny, single-celled organisms whose genetic material is loose in the cell. The genetic material of plants, animals, and other eukaryotes (true nucleus), on the other hand, is held in the cell's nucleus. While the Monera were briefly understood to be one of five biological kingdoms, it is now understood to comprise two domains: the bacteria and the archaea. The Monera kingdom included most organisms with a prokaryotic cell organization (that is, no nucleus). For this reason, the kingdom was sometimes called Prokaryota or Prokaryotae. Recent DNA and RNA sequence analyses has demonstrated that there are two major groups of prokaryotes, the Bacteria and Archaea, which do not appear to be closer in relationship to each other than they are to the Eukaryotes. Thus, Monera has since been divided into Archaea and Bacteria, forming the more recent six-kingdom system and three-domain system. All new schemes abandon the Monera and now treat the Bacteria, Archaea, and Eukarya as separate domains or kingdoms. Prior to the five-kingdom model with its Monera kingdom, these organisms were classifies as two separate divisions of plants: the Schizomycetes (bacteria) were considered fungi, and the Cyanophyta were considered blue-green algae. The latter are now considered a group of bacteria, typically called the cyanobacteria and are now known not to be closely related to plants, fungi, or animals. # Further Classification Based on molecular phylogeny studies, Carl Woese proposed that the prokaryotes (monerans) be divided into two separate groups: Bacteria and Archaea. In Carl Woese's 1990 proposed phylogeny[1], these three kingdoms are all rooted in a universal common ancestor and this is the most widely accepted categorical phylogeny accepted today. However, the most modern interpretation for these three kingdoms is the "Universal and Eukaryote Phylogenetic Tree" based on 16s rDNA, as presented in the Tree of Life Web Project.[2] ## Bacteria and Archaea Eubacteria and Archaebacteria differ most noticeably in the environments they are able to inhabit. Eubacteria encompass the vast majority of bacteria that come into contact with humans. The bacteria that live within and around humans, such as Escherichia coli and those of the genus Salmonella, are Eubacteria. Archaebacteria live in much harsher conditions, such as in acidic hot springs and at depths of a mile below the arctic ice. These groups were later renamed to Bacteria and Archaea, which might lead to some confusing situations, as the common use of the word "bacteria" in the English language (originally) simply refers to prokaryote microorganisms, or in other words monerans. # History - Traditionally organisms were classified as animal, vegetable, or mineral as in Systema Naturae. After the discovery of microscopy, attempts were made to fit microscopic organisms into either the plant or animal kingdom. In 1866 Ernst Haeckel proposed a three kingdom system which added Protista as a new kingdom that contained most microscopic organisms.[3] One of his eight major divisions of Protista was called Moneres. Haeckel's Moneres subcategory included known bacterial groups such as Vibrio. Haeckel's Protista kingdom also included eukaryotic organisms now classified as Protist. It was later decided that Haeckel's Protista kingdom had proven to be too diverse to be seriously considered one single kingdom. - In 1969, Robert Whittaker published a proposed five kingdom system for classification of living organisms.[4] Whittaker's system placed most single celled organisms into either the prokaryotic Monera or the eukaryotic Protista. The other three kingdoms in his system were the eukaryotic Fungi, Animalia, and Plantae. # Summary Template:Biological systems	https://www.wikidoc.org/index.php/Monerans
958058fa1dab3f30771f0ffc1ca604752ad7fbef	wikidoc	Monocane	Monocane Monocane is a fictional drug in the 1933 film The Invisible Man. In that film's sequel, The Invisible Man Returns, its name is changed to Duocane. Described by Dr. Cranley as "terrible," monocane was an obscure Indian drug with powerful bleaching properties. German scientists experimenting with it tried it on a dog, turning the animal dead white and driving it mad. Monocane was used by Dr. Jack Griffin as a key ingredient in his invisibility formula (something he did without knowing about monocane's ghastly side effects). Years later, Griffin's brother Frank's used the drug in his experiments as well. - Monocane was also identified as the poison used to murder the victim during the Matlock episode "The Hucksters". - Monocane was also identified as the poison used to murder the victim during the Perry Mason made-for-TV movie "A Perry Mason Mystery: The Case of the Lethal Lifestyle" (1994). - Monocane was also identified as the poison used to murder the victim in the McBride (TV series) made-for-TV episode, "The Doctor is Out… Really Out" (2005).	Monocane Monocane is a fictional drug in the 1933 film The Invisible Man. In that film's sequel, The Invisible Man Returns, its name is changed to Duocane. Described by Dr. Cranley as "terrible," monocane was an obscure Indian drug with powerful bleaching properties. German scientists experimenting with it tried it on a dog, turning the animal dead white and driving it mad. Monocane was used by Dr. Jack Griffin as a key ingredient in his invisibility formula (something he did without knowing about monocane's ghastly side effects). Years later, Griffin's brother Frank's used the drug in his experiments as well. - Monocane was also identified as the poison used to murder the victim during the Matlock episode "The Hucksters". - Monocane was also identified as the poison used to murder the victim during the Perry Mason made-for-TV movie "A Perry Mason Mystery: The Case of the Lethal Lifestyle" (1994). - Monocane was also identified as the poison used to murder the victim in the McBride (TV series) made-for-TV episode, "The Doctor is Out… Really Out" (2005). Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Monocane
f73141c98da8f03781c656e8c7e5030cc4b9bc1b	wikidoc	Monocyte	Monocyte Synonyms and keywords: mononuclear cell, monocyte # Overview A monocyte is a leukocyte, part of the human body's immune system that protects against blood-borne pathogens and moves quickly (aprox. 8-12 hours) to sites of infection in the tissues. Monocytes are usually identified in stained smears by their large bilobate nucleus. # Physiology Monocytes are produced by the bone marrow from haematopoietic stem cell precursors called monoblasts. Monocytes circulate in the bloodstream for about one to three days and then typically move into tissues throughout the body. They constitute between three to eight percent of the leukocytes in the blood. In the tissues monocytes mature into different types of macrophages at different anatomical locations. Monocytes are responsible for phagocytosis (ingestion) of foreign substances in the body. Monocytes can perform phagocytosis using intermediary (opsonising) proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern-recognition receptors that recognize pathogens. Monocytes are also capable of killing infected host cells via antibody, termed antibody-mediated cellular cytotoxicity. Vacuolization may be present in a cell that has recently phagocytized foreign matter. Monocytes which migrate from the bloodstream to other tissues are called macrophages. Macrophages are responsible for protecting tissues from foreign substances but are also suspected to be the predominant cells involved in triggering atherosclerosis. They are cells that possess a large smooth nucleus, a large area of cytoplasm and many internal vesicles for processing foreign material. # Diagnostic use A monocyte count is part of a complete blood count and is expressed either as a ratio of monocytes to the total number of white blood cells counted, or by absolute numbers. Both may be useful in determining or refuting a possible diagnosis. Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states. Examples of processes that can increase a monocyte count include: - chronic inflammation - stress response - hyperadrenocorticism - immune-mediated disease - pyogranulomatous disease - necrosis - red cell regeneration # Dendritic cells Monocytes can be used to generate dendritic cells in vitro.	Monocyte Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: mononuclear cell, monocyte # Overview A monocyte is a leukocyte, part of the human body's immune system that protects against blood-borne pathogens and moves quickly (aprox. 8-12 hours) to sites of infection in the tissues. Monocytes are usually identified in stained smears by their large bilobate nucleus. # Physiology Monocytes are produced by the bone marrow from haematopoietic stem cell precursors called monoblasts. Monocytes circulate in the bloodstream for about one to three days and then typically move into tissues throughout the body. They constitute between three to eight percent of the leukocytes in the blood. In the tissues monocytes mature into different types of macrophages at different anatomical locations. Monocytes are responsible for phagocytosis (ingestion) of foreign substances in the body. Monocytes can perform phagocytosis using intermediary (opsonising) proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern-recognition receptors that recognize pathogens. Monocytes are also capable of killing infected host cells via antibody, termed antibody-mediated cellular cytotoxicity. Vacuolization may be present in a cell that has recently phagocytized foreign matter. Monocytes which migrate from the bloodstream to other tissues are called macrophages. Macrophages are responsible for protecting tissues from foreign substances but are also suspected to be the predominant cells involved in triggering atherosclerosis. They are cells that possess a large smooth nucleus, a large area of cytoplasm and many internal vesicles for processing foreign material. # Diagnostic use A monocyte count is part of a complete blood count and is expressed either as a ratio of monocytes to the total number of white blood cells counted, or by absolute numbers. Both may be useful in determining or refuting a possible diagnosis. Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states. Examples of processes that can increase a monocyte count include: - chronic inflammation - stress response - hyperadrenocorticism - immune-mediated disease - pyogranulomatous disease - necrosis - red cell regeneration # Dendritic cells Monocytes can be used to generate dendritic cells in vitro.	https://www.wikidoc.org/index.php/Monocyte
fda2fe950491613cae2101f61b948896658cfc60	wikidoc	Monosomy	Monosomy # Overview Monosomy is a form of aneuploidy with the presence of only one chromosome (instead of the typical two in humans) from a pair. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies. ### Human monosomy Human conditions due to monosomy: - Turner syndrome - Women with Turner syndrome typically have one X chromosome instead of the usual two. Turner syndrome is the only full monosomy that is seen in humans. - Cri du chat syndrome -- (French for "cry of the cat" after the distinctive noise by affected persons' malformed larynx) a partial monosomy caused by a deletion of the end of the short p (from the word petit, French for small) arm of chromosome 5 - 1p36 Deletion Syndrome -- a partial monosomy caused by a deletion at the end of the short p arm of chromosome 1	Monosomy # Overview Monosomy is a form of aneuploidy with the presence of only one chromosome (instead of the typical two in humans) from a pair.[1] Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies. ### Human monosomy Human conditions due to monosomy: - Turner syndrome - Women with Turner syndrome typically have one X chromosome instead of the usual two. Turner syndrome is the only full monosomy that is seen in humans. - Cri du chat syndrome -- (French for "cry of the cat" after the distinctive noise by affected persons' malformed larynx) a partial monosomy caused by a deletion of the end of the short p (from the word petit, French for small) arm of chromosome 5 - 1p36 Deletion Syndrome -- a partial monosomy caused by a deletion at the end of the short p arm of chromosome 1	https://www.wikidoc.org/index.php/Monosomies
fe7fe296c40cd256fdce96fa128330925021c6ac	wikidoc	Mosquito	Mosquito The mosquitos are insects which make up the family Culicidae. They have a pair of scaled wings, a pair of halteres, a slender body, and long legs. The females of most mosquito species suck blood (hematophagy) from other animals, which has made them one of the most deadly disease vectors known to man, killing millions of people over thousands of years and continuing to kill millions per year by the spread of diseases. Length varies but is rarely greater than 16 mm (0.6 inch), and weight up to 2.5 mg (0.04 grain). A mosquito can fly for 1 to 4 hours continuously at up to 1-2 km/h travelling up to 10 km in a night. Most species are nocturnal or crepuscular (dawn or evening) feeders. During the heat of the day most mosquitos rest in a cool place and wait for the evenings. They may still bite if disturbed. # Evolution Mosquitos are believed to have evolved around 170 million years ago during the Jurassic era (199–144 million years ago) with the earliest known fossils from the Cretaceous era (144–65 million years ago). They are thought to have evolved in South America, spreading initially to the northern continent Laurasia and re-entering the tropics from the north. Some ancestral mosquitos were about three times the size of the extant species. The family Culicidae, a sister group to the Chaoboridae (biting midges), belongs to the order Diptera and contains about 3,500 species in three subfamilies: Anophelinae (3 genera), the Culicinae (at least 37 genera and >80% of all the species) and the Toxorhynchitinae (1 genus). The genera include Anopheles, Culex, Psorophora, Ochlerotatus, Aedes, Sabethes, Wyeomyia, Culiseta, and Haemagoggus. Within the subfamily Anophelinae six subgenera are recognized: Stethomyia, Lophopodomyia, Kerteszia, Nyssorhynchus (all South American), Cellia (Old World only), and Anopheles (worldwide). # Food habits Both male and female mosquitos are nectar feeders, but the female is also capable of haematophagy (drinking blood). Females do not require blood for survival, but they do need supplemental protein for the development and laying of their eggs. Prior to sucking the blood, they inject a mild painkiller, which numbs the host to the pain from the "bite" (Note: mosquitos do not actually bite). The Toxorhynchites species of mosquito never drinks blood. This genus includes the largest of the extant mosquitos, the larvae of which are predatory on the larvae of other mosquitos. These mosquito eaters have been used in the past as mosquito control agents, with varying success # Origin of the name Mosquito In the Spanish language, the word Mosquito (little fly) dates back to about 1572. The word was adopted to replace the term "biting flies" to prevent confusion with the house fly. It is derived from the word fly (Latin musca, cf. Skt maksh) and is related to the Italian moschetta and the French moustique. Mosquitoes were originally called "les moucherons" or "les cousins" by French writers, "Stechmücken" or "Schnaken" by Germans, "mygg" and "mygga" by Scandinavians, and "κώνωψ" (konops) by the ancient Greeks. The Scandinavian word is related to the Modern Greek word "μύγα" (myga) for the housefly. The Icelandic "mý" mostly stands for biting midges or non-biting chironomids, as there are no mosquitos in Iceland. Aristotle referred to mosquitoes in 300 B.C. as "empis". # Biology ## Anatomy The mosquito's head is mostly eye. Each eye is made up of many tiny lenses forming a compound eye. This type of eye allows for a very broad field of vision that easily detects movement. The mosquito lower body is mostly its stomach, which expands as it ingests its prey's blood. ## Life cycle and feeding habits In its life cycle the mosquito undergoes complete metamorphosis, going through four distinct stages: egg, larva, pupa, and adult, first described by the Greek philosopher Aristotle. ### Egg Female mosquitoes lay their eggs one at a time or together in rafts of a hundred or more eggs on the surface in fresh or any stagnant water. Anopheles and Aedes mosquitoes do not make egg rafts but lay their eggs separately. Culex, Culiseta, and Anopheles lay their eggs on water while Aedes lay their eggs on damp soil that is periodically flooded by water. Most eggs hatch into larvae in about 48 hours. A female mosquito may lay a raft of eggs every third night during its life span if it can find enough blood to develop the eggs. ### Larva The hatching eggs turn into larvae that live in the water, coming to the surface to breathe. As they grow they shed or moult their skin about four times growing larger after each moulting. Most larvae use siphon tubes going to the water surface for breathing and hang on or near the water surface. Anopheles larvae do not have a siphon and typically lie parallel to the water surface. The larvae eat micro-organisms and organic matter in the water for food. Mosquito larvae, commonly called "wigglers" or "wrigglers", must live in water from 7 to 14 days depending on the water's temperature. At their last moult they may be up to 1 cm or 1/2 inch long. In each stage they may be eaten by other insects or fish. Mosquito larvae in the genus Toxorhynchites eat other mosquito larvae. The length of the first three stages is dependent on the species and temperature, with lower temperatures increasing the length of the development stage. Culex tarsalis may complete its life cycle in 14 days at 20 C (68 F) and only ten days at 25 C (77 F). Some species have a life cycle of as little as four days, whereas in other species some adult females can live through the winter, laying their eggs in the spring. Many species of mosquito live their adult stage in roughly two weeks to two months. The larvae are the "wrigglers" found in puddles or water-filled containers. These breathe air through a siphon at the tail end. The pupae, or "tumblers", are nearly as active as the larvae, but breathe through thoracic "horns" attached to the thoracic spiracles. Most larvae feed on micro-organisms, but a few are predatory on other mosquito larvae. Some mosquito larvae, such as those of Wyeomyia live in unusual situations. These mosquito wigglers live either in the water collected in epiphytic bromeliads or inside water stored in carnivorous pitcher plants. Larvae of the genus Deinocerites live in crab holes along the edge of the ocean. On the fourth molt the larva changes into a pupa. ### Pupa The pupae are lighter than water and float on the surface as the mosquito larva metamorphoses (changes) into an adult mosquito in about two days. ### Adult The newly emerged adult must rest on the surface of the water for a short time to allow itself to dry and all its parts to harden before it can fly. This requires still water: mosquitoes do not breed in fast-moving water. The total time to go through all four stages depends on the temperature and the type of mosquito, but typically takes 14 days or less in warmer weather. In various species the time varies from 4 to 30 days. Most mosquito species outside of the tropics overwinter as eggs, but many overwinter as larvae or adults. Mosquitoes of the genus Culex (a vector for St. Louis encephalitis) overwinter as mated adult females. Most mosquitoes stay fairly close to the ground and do not range too far from where they were born, but may be dispersed long distances by wind. Mosquitoes are not strong flyers making only 1-2 km/h, (1-1.5 mph) therefore an electric fan may suffice as an effective mosquito screen. They feed mostly in the mornings and evenings and occasionally at night; avoiding the heat of the day. During the day they usually find somewhere cool to rest. Only female mosquitoes bite animals to get blood needed to produce eggs. Male mosquitoes do not bite, but both the male and female feed on the nectar of flowers for food. In most female mosquitoes, the mouth parts form a long proboscis for piercing the skin of mammals (or in some cases birds or even reptiles and amphibians) to suck their blood. As opposed to a syringe's typically smooth needle, the mosquito proboscis is highly serrated, which leaves a minimal number of points of contact with the skin being pierced — this reduces nerve stimulation to the point where the "bite" is typically not felt at all. (See the Mosquitoes and health section below for an explanation on the swelling). The females require protein for egg development and laying, and since the normal mosquito diet consists of nectar and fruit juice, which has no protein, most females must drink blood to lay eggs. Males differ from females, with mouth parts not suitable for blood-sucking. The female mosquitoes locate their next blood donor victims primarily through scent. They are extremely sensitive to the carbon dioxide in exhaled breath, as well as several substances found in sweat and various body odours. They are believed to be able to track potential prey for tens of meters. Some people attract more mosquitoes than others, apparently based on how they "smell" to a mosquito. Mosquitoes can also detect heat, so they can find warm-blooded mammals and birds very easily once they get close enough. Repellents like DEET work by disorienting the mosquito as it gets close to its potential next meal but do not kill mosquitoes. Surprisingly this works about 95% of the time. Male mosquitoes are distinctly smaller than females, with features such as feathered antennae and having no audible sound during flight. Female mosquitoes in flight emit a distinctive high-pitched buzz, which can interrupt sleep. # Mosquitoes and humans ## Mosquitoes and health File:Yellow fever Africa 2005.pngFile:Yellow fever South America 2005.png Mosquitoes are a vector agent that carries disease-causing viruses and parasites from person to person without catching the disease themselves. Female mosquitoes suck blood from people and other animals as part of their eating and breeding habits. The female mosquito that bites an infected person and then bites an uninfected person might leave traces of virus or parasite from the infected person's blood. The infected blood is injected through, or on, the "dirty" proboscis into the uninfected person's blood and the disease is thus spread from person to person. When a mosquito bites, she also injects saliva and anti-coagulants into the blood which may also contain disease-causing viruses or other parasites. This cycle can be interrupted by killing the mosquitoes, isolating infected people from all mosquitoes while they are infectious or vaccinating the exposed population. All three techniques have been used, often in combination, to control mosquito transmitted diseases. Window screens, introduced in the 1880s, were called "the most humane contribution the 19th century made to the preservation of sanity and good temper." Mosquitoes are estimated to transmit disease to more than 70 million people annually in Africa, South America, Central America, Mexico and much of Asia with millions of resulting deaths. In Europe, Russia, Greenland, Canada, the United States, Australia, New Zealand, the UK, Japan and other temperate and developed countries, mosquito bites are now mostly an irritating nuisance; but still cause some deaths each year. Historically, before mosquito transmitted diseases were brought under control, they caused tens of thousands of deaths in these countries and hundreds of thousands of infections. Mosquitoes were shown to be the method by which yellow fever and malaria were transmitted from person to person by Walter Reed, William C. Gorgas and associates in the U.S. Army Medical Corps first in Cuba and then around the Panama Canal in the early 1900s. Since then other diseases have been shown to be transmitted the same way. The mosquito genus Anopheles carries the malaria parasite (see Plasmodium). Worldwide, malaria is a leading cause of premature mortality, particularly in children under the age of five, with around 5.3 million deaths annually, according to the Centers for Disease Control. Most species of mosquito can carry the filariasis worm, a parasite that causes a disfiguring condition (often referred to as elephantiasis) characterized by a great swelling of several parts of the body; worldwide, around 40 million people are living with a filariasis disability. The viral diseases yellow fever and dengue fever are transmitted mostly by Aedes aegypti mosquitoes. Other viral diseases like epidemic polyarthritis, Rift Valley fever, Ross River Fever, St. Louis encephalitis, West Nile virus (WNV), Japanese encephalitis, LaCross encephalitis and several other encephalitis type diseases are carried by several different mosquitoes. Eastern equine encephalitis (EEE) and Western equine encephalitis (WEE) occurs in the United States where it causes disease in humans, horses, and some bird species. Because of the high mortality rate, EEE and WEE are regarded as two of the most serious mosquito-borne diseases in the United States. Symptoms range from mild flu-like illness to encephalitis, coma and death. Viruses carried by arthropods such as mosquitoes or ticks are known collectively as arboviruses. West Nile virus was accidentally introduced into the United States in 1999 and by 2003 had spread to almost every state with over 3,000 cases in 2006. A mosquito's period of feeding is often undetected; the bite only becomes apparent because of the immune reaction it provokes. When a mosquito bites a human, she injects saliva and anti-coagulants. For any given individual, with the initial bite there is no reaction but with subsequent bites the body's immune system develops antibodies and a bite becomes inflamed and itchy within 24 hours. This is the usual reaction in young children. With more bites, the sensitivity of the human immune system increases, and an itchy red hive appears in minutes where the immune response has broken capillary blood vessels and fluid has collected under the skin. This type of reaction is common in older children and adults. Some adults can become desensitized to mosquitoes and have little or no reaction to their bites, while others can become hyper-sensitive with bites causing blistering, bruising, and large inflammatory reactions. ## Mosquito control and integrated mosquito management There are two kinds of mosquito control: large, organized programs to reduce mosquito populations over a wide area, and actions individuals can take to control mosquitoes with respect to themselves and their own property. Organized mosquito control programs today draw on the principles of integrated pest management. An integrated mosquito control program typically includes the following measures, all guided by surveillance of mosquito populations and knowledge of the mosquito life cycle: - source reduction - the removal of mosquito breeding habitats - habitat modification - manipulating habitats to reduce breeding - biocontrol - introducing natural predators of mosquitoes - larvicide - using pesticides to reduce larval populations - adulticide - using pesticides to reduce adult populations Some solutions for malaria control efforts in the third world are: mosquito nets (klamboe), mosquito nets treated with insecticide (often permethrin), and DDT. Nets are treated with insecticide because mosquitoes can sometimes get past an imperfect net. Insecticide-treated nets (ITN) are estimated to be twice as effective as untreated nets in preventing mosquito bites. Untreated mosquito nets are less expensive, and they are effective in protecting humans when the nets do not have any holes and are tightly sealed around the edges. Insecticide free nets do not adversely affect the health of natural predators such as dragonflies. The role of DDT in combating mosquitoes has been the subject of considerable controversy. While some argue that DDT deeply damages biodiversity, others argue that DDT is the most effective weapon in combating mosquitoes and hence malaria. While some of this disagreement is based on differences in the extent to which disease control is valued as opposed to the value of biodiversity, there is also genuine disagreement amongst experts about the costs and benefits of using DDT. Moreover, DDT-resistant mosquitoes have started to increase in numbers, especially in tropics due to mutations, reducing the effectiveness of this chemical. ## Mosquito repellents and personal mosquito control A screened mosquito-proof room or house is one of the best and safest ways to sleep and still get ventilation for cooling. Mosquito netting if properly used and maintained (no holes), provides the maximum possible personal protection against biting insects. When not in use, mosquito nets are compact and surprisingly light-weight — about 0.5 kg. They can be used under almost any conditions to provide reliable protection against a wide range of biting insects. In many areas of the world, biting insects are not only a nuisance, but also pose a serious health threat. Sleeping under a bednet is highly recommended by the World Health Organization (WHO) and the U.S. Center for Disease Control (CDC) (and many others) if staying in these areas. The “gold standard” of mosquito repellents is N,N-diethyl-meta-toluamide, commonly known as DEET. It has been used widely since its invention by the U.S. Department of Agriculture in 1945. It is safe to use as directed, as verified by the CDC, the EPA, the U.S. Army and many others. It should not be applied around the eyes or in cuts and may irritate a few people’s skin. Solutions containing above 50% DEET gave maximum protection of about 12 hours before needing to be re-applied. Thirty percent DEET was good for about 6 hours, 20% about 3 hours and 7% DEET solutions only gave about 1 hour of protection. Apparently there is a minimum concentration needed for DEET to work effectively. DEET can damage certain plastics and varnishes, so care must be used when applying and using it. It should be applied by adults on children and its directions need to be followed. DEET can and should be applied with a good, long-lasting sun screen lotion. It should be removed by soap and water after use. DEET products have been widely used for many years but these products have occasionally been associated with some adverse reactions. DEET concentrations range from a low of about five percent up to 100 percent. Skin reactions (particularly at DEET concentrations of 50 percent and above) and eye irritation have been the most frequently reported adverse effects. There have been some reports of central nervous system problems, more frequently reported in children than adults, ranging from slurred speech and confusion to seizures and coma. The use of DEET products primarily results in exposure from skin contact, although unintentional exposure by breathing and ingestion can also occur. Other mosquito repellents than DEET do work but typically not as effectively and for only a few minutes to a few hours at best. If used they should be frequently re-applied. Examples include: catnip oil extract, nepetalactone (no known credible tests), citronella (10% solution, 84% effective for about 1 hour, DEET 96% effective, or eucalyptus oil extract. Soy bean oil (in Bite Blocker for Kids) worked for about 1 ½ hours and Repel’s plant-based lemon eucalyptus solution worked for about 3 hours. Oils of Syzygium aromaticum (clove) and Zanthoxylum limonella (makaen), widely used essential oils for dental caries or flavoring of food in Thailand, were prepared as 10 experimental repellent products in gel or cream form against Aedes aegypti, Culex quinquefasciatus, and Anopheles dirus under laboratory conditions, using the human-arm-in-cage method. Two products that gave the longest-lasting complete protection were selected to examine their repellency against a variety of mosquito species under field conditions. In laboratory tests, 0.1 g of each product was applied to 3x10 cm of exposed area on a volunteer's forearm, while in field trials, 1.0 g was applied to each volunteer's leg (from knee to ankle). In the laboratory, the gel dosage form contained 20% clove oil (Gel B) or 10% clove plus 10% makaen oil mixture (Gel E) were promising plant-based repellents against three mosquito species and gave significantly longer complete protection times of 4-5 hours than all other developing products. Therefore, their efficacy in the field was evaluated. Under field conditions, Gel E showed complete protection for 4 hours and gave 95.7% repellency after 5 hours application, whereas Gel B and 20% deet (di-methyl benzamide) provided only 86.8 and 82.7% repellency after treatment, respectively against Ae. aegypti, daytime-biting mosquitos. For nighttime-biting, the 3 repellents under development yielded equally excellent (average 97.1%) repellency for 5 hours against the predominant Cx. quinquefasciatus and Mansonia uniformis, but they gave 89.0% repellency against Cx. tritaeniorhynchus and Cx. gelidus. This finding demonstrated the effectiveness of Gel B and Gel E products for possible use by low-income rural communities against various mosquito species. Picaridin, first used in Europe in 2001, has been reported to be effective by Consumer Reports (7% solution) and the Australian Army (20% solution). Consumer Report retests in 2006 show that a 7% solution of picaridin now has a protection time of about 0 minutes and a 15% solution was only good for about one hour. So far DEET is the champion effective repellent against mosquitoes, especially when worn in conjunction with light coloured clothing, long sleeved pants and shirts and a hat. Other commercial products offered for household mosquito "control" include small electrical mats, mosquito repellent vapor, DEET-impregnated wrist bands, and mosquito coils containing a form of the chemical allethrin. Mosquito-repellent candles containing citronella oil are sold widely in the U.S. All of these have been used with mixed reports of success and failure. Some claim that plants like wormwood or sagewort, lemon balm, lemon grass, lemon thyme and the mosquito plant (Pelargonium) will act against mosquitoes. However, scientists have determined that these plants are “effective” for a limited time only when the leaves are crushed and applied directly to the skin. There are several, widespread, unproven theories about mosquito control such as the assertion that Vitamin B, in particular B1 Thiamine, garlic, ultrasonic devices, incense, can be used to repel or control mosquitoes. Moreover, some manufacturers of "mosquito repelling" ultrasonic devices have been found to be fraudulent, and their devices were deemed "useless" in tests by the UK Consumer magazine Which? The Dragonfly eats mosquitos at all stages of development and is quite effective in controlling populations. Although bats and Purple Martins can be prodigious consumers of insects, many of which are pests, less than 1% of their diet typically consists of mosquitoes. Bats are known carriers of rabies, and neither they nor Purple Martins are known to control or even significantly reduce mosquito populations. Similarly, bug zappers kill a wide range of flying insects including many beneficial insects that eat mosquitoes as well as some mosquitoes. Bug zappers have not been proven effective at controlling mosquito populations. Some newer mosquito traps or known mosquito attractants emit a plume of carbon dioxide together with other mosquito attractants such as sugary scents, lactic acid, octenol, warmth, water vapor and sounds. By mimicking a mammal’s scent and outputs, female mosquitoes are drawn toward the trap, where they are typically sucked into a net or holder by an electric fan where they are collected. According to the American Mosquito Control Association, "these devices will, indeed, trap and kill measurable numbers of mosquitoes," but their effectiveness in any particular case will depend on a number of factors such as the size and species of the mosquito population and the type and location of the breeding habitat. They are useful in specimen collection studies to determine the types of mosquitoes prevalent in an area but are typically far too inefficient to be useful in reducing mosquito populations. ## Treatment of mosquito bites Visible, irritating bites are due to an immune response from the binding of IgG and IgE antibodies to antigens in the mosquito's saliva. Some of the sensitizing antigens are common to all mosquito species, whereas others are specific to certain species. There are both immediate hypersensitivity reactions (Types I & III) and delayed hypersensitivity reactions (Type IV) to mosquito bites (see Clements, 2000). There are several commercially available anti-itch medications. These are usually orally or topically applied antihistamines and, for more severe cases, corticosteroids such as hydrocortisone and triamcinolone. Many home remedies are effective against itching, including calamine lotion, baking soda, rubbing alcohol, and vinegar. Ammonia is another ingredient in commercial mosquito bite treatments (e.g. Afterbite). Ammonia has been clinical demonstrated to be an effective treatment. Scratching and cooling are effective but bring relief for only a short time. Another proven remedy for the itch is applying heat directly to the bite. Common methods for applying heat treatment include running hot water from a faucet over the irritated skin or heating a mug of water in a microwave for 1 to 2 minutes and then holding the hot mug against the bite for at least 1 minute. Caution: only apply heat that is tolerable; be sure not to burn or blister the skin. ## Cultural views According to the “Mosquitoes” chapter in Kwaidan: Stories and Studies of Strange Things, by Lafcadio Hearn (1850–1904), mosquitoes are seen as reincarnations of the dead, condemned by the errors of their former lives to the condition of Jiki-ketsu-gaki, or "blood-drinking pretas". The Babylonian Talmud (Gittin 56b) asserts that the Roman Emperor Titus was punished by God for having destroyed the Temple in Jerusalem by having a mosquito fly into Titus' nose, picking at his brain, ceaselessly buzzing, driving him crazy and eventually causing his death. No such account appears in any Roman source, but it is quite well known that Titus died prematurely, after only two years in power, from unclear causes. In contemporary culture, Mosquitoes are sometimes seen as a source of humor. For example, There's a Skeeter on My Peter is a well-known humorous song. Additionally, some individuals jokingly suggest that the mosquito is the state bird of Florida, Minnesota, or Alaska (see list of U.S. state birds for more information on this longstanding joke). Moreover, mosquito jokes constitute a distinct genre of humor. # Systematics - Subfamily Anophelinae - Anopheles - Bironella - Chagasia - Subfamily Culicinae - Aedeomyia - Aedes (sometimes divided with Ochlerotatus). - Armigeres - Ayurakitia - Coquillettidia - Culex - Culiseta - Deinocerites - Eretmapodites - Ficalbia - Galindomyia - Haemagogus - Heizmannia - Hodgesia - Isostomyia - Johnbelkinia - Limatus - Lutzia - Malaya - Mansonia - Maorigoeldia - Mimomyia - Onirion - Opifex - Orthopodomyia - Psorophora - Runchomyia - Sabethes - Shannoniana - Topomyia - Trichoprosopon - Tripteroides - Udaya - Uranotaenia - Verrallina - Wyeomyia - Zeugnomyia - Subfamily Toxorhynchitinae - Toxorhynchites # Identification - Brunhes, J.; Rhaim, A.; Geoffroy, B. et al. Les Moustiques de l'Afrique mediterraneene French/English. Interactive identification guide to mosquitoes of North Africa, with database of information on morphology, ecology, epidemiology, and control. Mac/PC Numerous illustrations. IRD/IPT 2000 CD-ROM	Mosquito The mosquitos are insects which make up the family Culicidae. They have a pair of scaled wings, a pair of halteres, a slender body, and long legs. The females of most mosquito species suck blood (hematophagy) from other animals[1], which has made them one of the most deadly disease vectors known to man, killing millions of people over thousands of years and continuing to kill millions per year by the spread of diseases.[2][3] Length varies but is rarely greater than 16 mm (0.6 inch)[4], and weight up to 2.5 mg (0.04 grain). A mosquito can fly for 1 to 4 hours continuously at up to 1-2 km/h[5] travelling up to 10 km in a night. Most species are nocturnal or crepuscular (dawn or evening) feeders. During the heat of the day most mosquitos rest in a cool place and wait for the evenings. They may still bite if disturbed.[6] # Evolution Mosquitos are believed to have evolved around 170 million years ago during the Jurassic era (199–144 million years ago) with the earliest known fossils from the Cretaceous era (144–65 million years ago).[7] They are thought to have evolved in South America, spreading initially to the northern continent Laurasia and re-entering the tropics from the north.[8] Some ancestral mosquitos were about three times the size of the extant species.[citation needed] The family Culicidae, a sister group to the Chaoboridae (biting midges), belongs to the order Diptera and contains about 3,500 species in three subfamilies: Anophelinae (3 genera), the Culicinae (at least 37 genera and >80% of all the species) and the Toxorhynchitinae (1 genus). The genera include Anopheles, Culex, Psorophora, Ochlerotatus, Aedes, Sabethes, Wyeomyia, Culiseta, and Haemagoggus. Within the subfamily Anophelinae six subgenera are recognized: Stethomyia, Lophopodomyia, Kerteszia, Nyssorhynchus (all South American), Cellia (Old World only), and Anopheles (worldwide). # Food habits Both male and female mosquitos are nectar feeders, but the female is also capable of haematophagy (drinking blood). Females do not require blood for survival, but they do need supplemental protein for the development and laying of their eggs. Prior to sucking the blood, they inject a mild painkiller, which numbs the host to the pain from the "bite" (Note: mosquitos do not actually bite). The Toxorhynchites species of mosquito never drinks blood.[9] This genus includes the largest of the extant mosquitos, the larvae of which are predatory on the larvae of other mosquitos. These mosquito eaters have been used in the past as mosquito control agents, with varying success .[10] # Origin of the name Mosquito In the Spanish language, the word Mosquito (little fly) dates back to about 1572.[11] The word was adopted to replace the term "biting flies" to prevent confusion with the house fly. It is derived from the word fly (Latin musca, cf. Skt maksh) and is related to the Italian moschetta and the French moustique. Mosquitoes were originally called "les moucherons" or "les cousins" by French writers, "Stechmücken" or "Schnaken" by Germans, "mygg" and "mygga" by Scandinavians, and "κώνωψ" (konops) by the ancient Greeks. The Scandinavian word is related to the Modern Greek word "μύγα" (myga) for the housefly. The Icelandic "mý" mostly stands for biting midges or non-biting chironomids, as there are no mosquitos in Iceland.[12] Aristotle referred to mosquitoes in 300 B.C. as "empis". # Biology Template:Sectionstub ## Anatomy The mosquito's head is mostly eye. Each eye is made up of many tiny lenses forming a compound eye. This type of eye allows for a very broad field of vision that easily detects movement. The mosquito lower body is mostly its stomach, which expands as it ingests its prey's blood. [13] ## Life cycle and feeding habits In its life cycle the mosquito undergoes complete metamorphosis, going through four distinct stages: egg, larva, pupa, and adult, first described by the Greek philosopher Aristotle.[14] ### Egg Female mosquitoes lay their eggs one at a time or together in rafts of a hundred or more eggs on the surface in fresh or any stagnant water. Anopheles and Aedes mosquitoes do not make egg rafts but lay their eggs separately. Culex, Culiseta, and Anopheles lay their eggs on water while Aedes lay their eggs on damp soil that is periodically flooded by water. Most eggs hatch into larvae in about 48 hours. A female mosquito may lay a raft of eggs every third night during its life span if it can find enough blood to develop the eggs. ### Larva The hatching eggs turn into larvae that live in the water, coming to the surface to breathe. As they grow they shed or moult their skin about four times growing larger after each moulting. Most larvae use siphon tubes going to the water surface for breathing and hang on or near the water surface. Anopheles larvae do not have a siphon and typically lie parallel to the water surface. The larvae eat micro-organisms and organic matter in the water for food. Mosquito larvae, commonly called "wigglers" or "wrigglers", must live in water from 7 to 14 days depending on the water's temperature. At their last moult they may be up to 1 cm or 1/2 inch long. In each stage they may be eaten by other insects or fish. Mosquito larvae in the genus Toxorhynchites eat other mosquito larvae. The length of the first three stages is dependent on the species and temperature, with lower temperatures increasing the length of the development stage.[15] Culex tarsalis may complete its life cycle in 14 days at 20 C (68 F) and only ten days at 25 C (77 F). Some species have a life cycle of as little as four days, whereas in other species some adult females can live through the winter, laying their eggs in the spring. Many species of mosquito live their adult stage in roughly two weeks to two months. The larvae are the "wrigglers" found in puddles or water-filled containers. These breathe air through a siphon at the tail end. The pupae, or "tumblers", are nearly as active as the larvae, but breathe through thoracic "horns" attached to the thoracic spiracles. Most larvae feed on micro-organisms, but a few are predatory on other mosquito larvae. Some mosquito larvae, such as those of Wyeomyia live in unusual situations. These mosquito wigglers live either in the water collected in epiphytic bromeliads or inside water stored in carnivorous pitcher plants. Larvae of the genus Deinocerites live in crab holes along the edge of the ocean. On the fourth molt the larva changes into a pupa. ### Pupa The pupae are lighter than water and float on the surface as the mosquito larva metamorphoses (changes) into an adult mosquito in about two days. ### Adult The newly emerged adult must rest on the surface of the water for a short time to allow itself to dry and all its parts to harden before it can fly. This requires still water: mosquitoes do not breed in fast-moving water. The total time to go through all four stages depends on the temperature and the type of mosquito, but typically takes 14 days or less in warmer weather. In various species the time varies from 4 to 30 days. Most mosquito species outside of the tropics overwinter as eggs, but many overwinter as larvae or adults. Mosquitoes of the genus Culex (a vector for St. Louis encephalitis) overwinter as mated adult females. Most mosquitoes stay fairly close to the ground and do not range too far from where they were born, but may be dispersed long distances by wind. Mosquitoes are not strong flyers making only 1-2 km/h, (1-1.5 mph) therefore an electric fan may suffice as an effective mosquito screen. They feed mostly in the mornings and evenings and occasionally at night; avoiding the heat of the day. During the day they usually find somewhere cool to rest. Only female mosquitoes bite animals to get blood needed to produce eggs. Male mosquitoes do not bite, but both the male and female feed on the nectar of flowers for food. In most female mosquitoes, the mouth parts form a long proboscis for piercing the skin of mammals (or in some cases birds or even reptiles and amphibians) to suck their blood. As opposed to a syringe's typically smooth needle, the mosquito proboscis is highly serrated, which leaves a minimal number of points of contact with the skin being pierced — this reduces nerve stimulation to the point where the "bite" is typically not felt at all. (See the Mosquitoes and health section below for an explanation on the swelling). The females require protein for egg development and laying, and since the normal mosquito diet consists of nectar and fruit juice, which has no protein, most females must drink blood to lay eggs. Males differ from females, with mouth parts not suitable for blood-sucking. The female mosquitoes locate their next blood donor victims primarily through scent. They are extremely sensitive to the carbon dioxide in exhaled breath, as well as several substances found in sweat and various body odours. They are believed to be able to track potential prey for tens of meters. Some people attract more mosquitoes than others, apparently based on how they "smell" to a mosquito. Mosquitoes can also detect heat, so they can find warm-blooded mammals and birds very easily once they get close enough. Repellents like DEET work by disorienting the mosquito as it gets close to its potential next meal but do not kill mosquitoes. Surprisingly this works about 95% of the time.[citation needed] Male mosquitoes are distinctly smaller than females, with features such as feathered antennae and having no audible sound during flight. Female mosquitoes in flight emit a distinctive high-pitched buzz, which can interrupt sleep. # Mosquitoes and humans ## Mosquitoes and health File:Yellow fever Africa 2005.pngFile:Yellow fever South America 2005.png Mosquitoes are a vector agent that carries disease-causing viruses and parasites from person to person without catching the disease themselves. Female mosquitoes suck blood from people and other animals as part of their eating and breeding habits. The female mosquito that bites an infected person and then bites an uninfected person might leave traces of virus or parasite from the infected person's blood. The infected blood is injected through, or on, the "dirty" proboscis into the uninfected person's blood and the disease is thus spread from person to person. When a mosquito bites, she also injects saliva and anti-coagulants into the blood which may also contain disease-causing viruses or other parasites. This cycle can be interrupted by killing the mosquitoes, isolating infected people from all mosquitoes while they are infectious or vaccinating the exposed population. All three techniques have been used, often in combination, to control mosquito transmitted diseases. Window screens, introduced in the 1880s, were called "the most humane contribution the 19th century made to the preservation of sanity and good temper."[16] Mosquitoes are estimated to transmit disease to more than 70 million people annually in Africa, South America, Central America, Mexico and much of Asia with millions of resulting deaths. In Europe, Russia, Greenland, Canada, the United States, Australia, New Zealand, the UK, Japan and other temperate and developed countries, mosquito bites are now mostly an irritating nuisance; but still cause some deaths each year.[17] Historically, before mosquito transmitted diseases were brought under control, they caused tens of thousands of deaths in these countries and hundreds of thousands of infections.[18] Mosquitoes were shown to be the method by which yellow fever and malaria were transmitted from person to person by Walter Reed, William C. Gorgas and associates in the U.S. Army Medical Corps first in Cuba and then around the Panama Canal in the early 1900s.[19][20] Since then other diseases have been shown to be transmitted the same way. The mosquito genus Anopheles carries the malaria parasite (see Plasmodium). Worldwide, malaria is a leading cause of premature mortality, particularly in children under the age of five, with around 5.3 million deaths annually, according to the Centers for Disease Control. Most species of mosquito can carry the filariasis worm, a parasite that causes a disfiguring condition (often referred to as elephantiasis) characterized by a great swelling of several parts of the body; worldwide, around 40 million people are living with a filariasis disability. The viral diseases yellow fever and dengue fever are transmitted mostly by Aedes aegypti mosquitoes. Other viral diseases like epidemic polyarthritis, Rift Valley fever, Ross River Fever, St. Louis encephalitis, West Nile virus (WNV), Japanese encephalitis, LaCross encephalitis and several other encephalitis type diseases are carried by several different mosquitoes. Eastern equine encephalitis (EEE) and Western equine encephalitis (WEE) occurs in the United States where it causes disease in humans, horses, and some bird species. Because of the high mortality rate, EEE and WEE are regarded as two of the most serious mosquito-borne diseases in the United States. Symptoms range from mild flu-like illness to encephalitis, coma and death.[21] Viruses carried by arthropods such as mosquitoes or ticks are known collectively as arboviruses. West Nile virus was accidentally introduced into the United States in 1999 and by 2003 had spread to almost every state with over 3,000 cases in 2006. A mosquito's period of feeding is often undetected; the bite only becomes apparent because of the immune reaction it provokes. When a mosquito bites a human, she injects saliva and anti-coagulants. For any given individual, with the initial bite there is no reaction but with subsequent bites the body's immune system develops antibodies and a bite becomes inflamed and itchy within 24 hours. This is the usual reaction in young children. With more bites, the sensitivity of the human immune system increases, and an itchy red hive appears in minutes where the immune response has broken capillary blood vessels and fluid has collected under the skin. This type of reaction is common in older children and adults. Some adults can become desensitized to mosquitoes and have little or no reaction to their bites, while others can become hyper-sensitive with bites causing blistering, bruising, and large inflammatory reactions. ## Mosquito control and integrated mosquito management There are two kinds of mosquito control: large, organized programs to reduce mosquito populations over a wide area, and actions individuals can take to control mosquitoes with respect to themselves and their own property. Organized mosquito control programs today draw on the principles of integrated pest management. An integrated mosquito control program typically includes the following measures, all guided by surveillance of mosquito populations and knowledge of the mosquito life cycle:[22] - source reduction - the removal of mosquito breeding habitats - habitat modification - manipulating habitats to reduce breeding - biocontrol - introducing natural predators of mosquitoes - larvicide - using pesticides to reduce larval populations - adulticide - using pesticides to reduce adult populations Some solutions for malaria control efforts in the third world are: mosquito nets (klamboe), mosquito nets treated with insecticide (often permethrin), and DDT.[23] Nets are treated with insecticide because mosquitoes can sometimes get past an imperfect net. Insecticide-treated nets (ITN) are estimated to be twice as effective as untreated nets in preventing mosquito bites.[24] Untreated mosquito nets are less expensive, and they are effective in protecting humans when the nets do not have any holes and are tightly sealed around the edges. Insecticide free nets do not adversely affect the health of natural predators such as dragonflies. The role of DDT in combating mosquitoes has been the subject of considerable controversy. While some argue that DDT deeply damages biodiversity, others argue that DDT is the most effective weapon in combating mosquitoes and hence malaria. While some of this disagreement is based on differences in the extent to which disease control is valued as opposed to the value of biodiversity, there is also genuine disagreement amongst experts about the costs and benefits of using DDT. Moreover, DDT-resistant mosquitoes have started to increase in numbers, especially in tropics due to mutations, reducing the effectiveness of this chemical. ## Mosquito repellents and personal mosquito control Template:Ad A screened mosquito-proof room or house is one of the best and safest ways to sleep and still get ventilation for cooling. Mosquito netting if properly used and maintained (no holes), provides the maximum possible personal protection against biting insects. When not in use, mosquito nets are compact and surprisingly light-weight — about 0.5 kg. They can be used under almost any conditions to provide reliable protection against a wide range of biting insects. In many areas of the world, biting insects are not only a nuisance, but also pose a serious health threat. Sleeping under a bednet is highly recommended by the World Health Organization (WHO)[25] and the U.S. Center for Disease Control (CDC)[26] (and many others) if staying in these areas. The “gold standard” of mosquito repellents is N,N-diethyl-meta-toluamide, commonly known as DEET. It has been used widely since its invention by the U.S. Department of Agriculture in 1945. It is safe to use as directed, as verified by the CDC, the EPA,[27] the U.S. Army and many others. It should not be applied around the eyes or in cuts and may irritate a few people’s skin. Solutions containing above 50% DEET gave maximum protection of about 12 hours before needing to be re-applied. Thirty percent DEET was good for about 6 hours, 20% about 3 hours and 7% DEET solutions only gave about 1 hour of protection. Apparently there is a minimum concentration needed for DEET to work effectively. DEET can damage certain plastics and varnishes, so care must be used when applying and using it. It should be applied by adults on children and its directions need to be followed. DEET can and should be applied with a good, long-lasting sun screen lotion. It should be removed by soap and water after use. DEET products have been widely used for many years but these products have occasionally been associated with some adverse reactions. DEET concentrations range from a low of about five percent up to 100 percent. Skin reactions (particularly at DEET concentrations of 50 percent and above) and eye irritation have been the most frequently reported adverse effects. There have been some reports of central nervous system problems, more frequently reported in children than adults, ranging from slurred speech and confusion to seizures and coma. The use of DEET products primarily results in exposure from skin contact, although unintentional exposure by breathing and ingestion can also occur.[28] Other mosquito repellents than DEET do work but typically not as effectively and for only a few minutes to a few hours at best. If used they should be frequently re-applied. Examples include: catnip oil extract, nepetalactone (no known credible tests), citronella (10% solution, 84% effective for about 1 hour, DEET 96% effective[29], or eucalyptus oil extract.[30] Soy bean oil (in Bite Blocker for Kids) worked for about 1 ½ hours and Repel’s plant-based lemon eucalyptus solution worked for about 3 hours. Oils of Syzygium aromaticum (clove) and Zanthoxylum limonella (makaen), widely used essential oils for dental caries or flavoring of food in Thailand, were prepared as 10 experimental repellent products in gel or cream form against Aedes aegypti, Culex quinquefasciatus, and Anopheles dirus under laboratory conditions, using the human-arm-in-cage method. Two products that gave the longest-lasting complete protection were selected to examine their repellency against a variety of mosquito species under field conditions. In laboratory tests, 0.1 g of each product was applied to 3x10 cm of exposed area on a volunteer's forearm, while in field trials, 1.0 g was applied to each volunteer's leg (from knee to ankle). In the laboratory, the gel dosage form contained 20% clove oil (Gel B) or 10% clove plus 10% makaen oil mixture (Gel E) were promising plant-based repellents against three mosquito species and gave significantly longer complete protection times of 4-5 hours than all other developing products. Therefore, their efficacy in the field was evaluated. Under field conditions, Gel E showed complete protection for 4 hours and gave 95.7% repellency after 5 hours application, whereas Gel B and 20% deet (di-methyl benzamide) provided only 86.8 and 82.7% repellency after treatment, respectively against Ae. aegypti, daytime-biting mosquitos. For nighttime-biting, the 3 repellents under development yielded equally excellent (average 97.1%) repellency for 5 hours against the predominant Cx. quinquefasciatus and Mansonia uniformis, but they gave 89.0% repellency against Cx. tritaeniorhynchus and Cx. gelidus. This finding demonstrated the effectiveness of Gel B and Gel E products for possible use by low-income rural communities against various mosquito species. Picaridin, first used in Europe in 2001, has been reported to be effective by Consumer Reports (7% solution)[31] and the Australian Army (20% solution).[32] Consumer Report retests in 2006 show that a 7% solution of picaridin now has a protection time of about 0 minutes and a 15% solution was only good for about one hour.[33] So far DEET is the champion effective repellent against mosquitoes, especially when worn in conjunction with light coloured clothing, long sleeved pants and shirts and a hat. Other commercial products offered for household mosquito "control" include small electrical mats, mosquito repellent vapor, DEET-impregnated wrist bands, and mosquito coils containing a form of the chemical allethrin. Mosquito-repellent candles containing citronella oil are sold widely in the U.S. All of these have been used with mixed reports of success and failure. Some claim that plants like wormwood or sagewort, lemon balm, lemon grass, lemon thyme and the mosquito plant (Pelargonium) will act against mosquitoes. However, scientists have determined that these plants are “effective” for a limited time only when the leaves are crushed and applied directly to the skin.[34] There are several, widespread, unproven theories about mosquito control such as the assertion that Vitamin B, in particular B1 Thiamine, garlic, ultrasonic devices, incense, can be used to repel or control mosquitoes.[35] [36] Moreover, some manufacturers of "mosquito repelling" ultrasonic devices have been found to be fraudulent,[37] and their devices were deemed "useless" in tests by the UK Consumer magazine Which?[38] The Dragonfly eats mosquitos at all stages of development and is quite effective in controlling populations. Although bats and Purple Martins can be prodigious consumers of insects, many of which are pests, less than 1% of their diet typically consists of mosquitoes. Bats are known carriers of rabies, and neither they nor Purple Martins are known to control or even significantly reduce mosquito populations.[citation needed] Similarly, bug zappers kill a wide range of flying insects including many beneficial insects that eat mosquitoes as well as some mosquitoes. Bug zappers have not been proven effective at controlling mosquito populations. Some newer mosquito traps or known mosquito attractants emit a plume of carbon dioxide together with other mosquito attractants such as sugary scents, lactic acid, octenol, warmth, water vapor and sounds. By mimicking a mammal’s scent and outputs, female mosquitoes are drawn toward the trap, where they are typically sucked into a net or holder by an electric fan where they are collected. According to the American Mosquito Control Association,[39] "these devices will, indeed, trap and kill measurable numbers of mosquitoes," but their effectiveness in any particular case will depend on a number of factors such as the size and species of the mosquito population and the type and location of the breeding habitat. They are useful in specimen collection studies to determine the types of mosquitoes prevalent in an area but are typically far too inefficient to be useful in reducing mosquito populations. ## Treatment of mosquito bites Visible, irritating bites are due to an immune response from the binding of IgG and IgE antibodies to antigens in the mosquito's saliva. Some of the sensitizing antigens are common to all mosquito species, whereas others are specific to certain species. There are both immediate hypersensitivity reactions (Types I & III) and delayed hypersensitivity reactions (Type IV) to mosquito bites (see Clements, 2000). There are several commercially available anti-itch medications. These are usually orally or topically applied antihistamines and, for more severe cases, corticosteroids such as hydrocortisone and triamcinolone. Many home remedies are effective against itching, including calamine lotion, baking soda, rubbing alcohol, and vinegar. Ammonia is another ingredient in commercial mosquito bite treatments (e.g. Afterbite). Ammonia has been clinical demonstrated to be an effective treatment[40]. Scratching and cooling are effective but bring relief for only a short time. Another proven remedy for the itch is applying heat directly to the bite. Common methods for applying heat treatment include running hot water from a faucet over the irritated skin or heating a mug of water in a microwave for 1 to 2 minutes and then holding the hot mug against the bite for at least 1 minute. Caution: only apply heat that is tolerable; be sure not to burn or blister the skin. ## Cultural views According to the “Mosquitoes” chapter in Kwaidan: Stories and Studies of Strange Things, by Lafcadio Hearn (1850–1904), mosquitoes are seen as reincarnations of the dead, condemned by the errors of their former lives to the condition of Jiki-ketsu-gaki, or "blood-drinking pretas".[41] The Babylonian Talmud (Gittin 56b) asserts that the Roman Emperor Titus was punished by God for having destroyed the Temple in Jerusalem by having a mosquito fly into Titus' nose, picking at his brain, ceaselessly buzzing, driving him crazy and eventually causing his death. No such account appears in any Roman source, but it is quite well known that Titus died prematurely, after only two years in power, from unclear causes. In contemporary culture, Mosquitoes are sometimes seen as a source of humor. For example, There's a Skeeter on My Peter is a well-known humorous song. Additionally, some individuals jokingly suggest that the mosquito is the state bird of Florida, Minnesota, or Alaska (see list of U.S. state birds for more information on this longstanding joke). Moreover, mosquito jokes constitute a distinct genre of humor.[1][2] # Systematics - Subfamily Anophelinae - Anopheles - Bironella - Chagasia - Subfamily Culicinae - Aedeomyia - Aedes (sometimes divided with Ochlerotatus). - Armigeres - Ayurakitia - Coquillettidia - Culex - Culiseta - Deinocerites - Eretmapodites - Ficalbia - Galindomyia - Haemagogus - Heizmannia - Hodgesia - Isostomyia - Johnbelkinia - Limatus - Lutzia - Malaya - Mansonia - Maorigoeldia - Mimomyia - Onirion - Opifex - Orthopodomyia - Psorophora - Runchomyia - Sabethes - Shannoniana - Topomyia - Trichoprosopon - Tripteroides - Udaya - Uranotaenia - Verrallina - Wyeomyia - Zeugnomyia - Subfamily Toxorhynchitinae - Toxorhynchites # Identification - Brunhes, J.; Rhaim, A.; Geoffroy, B. et al. Les Moustiques de l'Afrique mediterraneene French/English. Interactive identification guide to mosquitoes of North Africa, with database of information on morphology, ecology, epidemiology, and control. Mac/PC Numerous illustrations. IRD/IPT [12640] 2000 CD-ROM	https://www.wikidoc.org/index.php/Mosquito
a58c81dc8af57b2162493a44f7b820a465c0d6f1	wikidoc	Mothball	Mothball Mothballs are small balls of chemical pesticide and deodorant used when storing clothing and other articles susceptible to damage from mold or moth larvae. Their use when clothing is stored out-of-season gave rise to the colloquial usage of the terms mothballed and put into mothballs to refer to anything which is put into storage or whose operation is suspended. # Composition and safety Older mothballs consisted primarily of naphthalene, but due to naphthalene's flammability, modern mothballs use 1,4-dichlorobenzene instead. Both of these ingredients have a strong, pungent odor often associated strongly with mothballs. Camphor, an insect repellent, can be used in mothballs also. The idea with both chemicals is to kill moths and moth larvae with the fumes. Both naphthalene and paradichlorobenzene sublimate, meaning they transition from a solid straight to a gas. The gas is toxic to the moths. For either of these chemicals to be effective, they need to be placed with the clothing in a sealed container so the fumes can build up and kill the moths. In a sealed atmosphere like this, the fumes are not harmful to people because they are contained. The main threat would occur when opening the containers, or from wearing clothes immediately after opening (especially a problem for infants). A solution is to open the containers outside and let the clothes hang and air out for a day before wearing. Adolescents have recently been found to use mothballs for huffing. Mothballs have also been found to be a carcinogen (i.e. a cancer-causing agent). # Other uses Mothballs can also be used as a snake repellent. Mothballs (or sulfur) is usually used along with the aid of naphtha for these purposes. When mixed together, the snake sampling the air senses its acrid stench and its scent sampling is overloaded by the stench. It can't sense prey or danger as well with this smell, so it turns away. Put the mothballs around the perimeter of your yard leaving an "escape" for the snakes to get away or they will be locked in your yard. Caution should be exercised, as mothballs are not child or pet friendly and they can kill some types of plants. Rain or water will disintegrate the mothballs, so frequent reapplication will be necessary.	Mothball Mothballs are small balls of chemical pesticide and deodorant used when storing clothing and other articles susceptible to damage from mold or moth larvae. Their use when clothing is stored out-of-season gave rise to the colloquial usage of the terms mothballed and put into mothballs to refer to anything which is put into storage or whose operation is suspended. # Composition and safety Older mothballs consisted primarily of naphthalene, but due to naphthalene's flammability, modern mothballs use 1,4-dichlorobenzene instead. Both of these ingredients have a strong, pungent odor often associated strongly with mothballs. Camphor, an insect repellent, can be used in mothballs also. The idea with both chemicals is to kill moths and moth larvae with the fumes. Both naphthalene and paradichlorobenzene sublimate, meaning they transition from a solid straight to a gas. The gas is toxic to the moths. For either of these chemicals to be effective, they need to be placed with the clothing in a sealed container so the fumes can build up and kill the moths. In a sealed atmosphere like this, the fumes are not harmful to people because they are contained. The main threat would occur when opening the containers, or from wearing clothes immediately after opening (especially a problem for infants). A solution is to open the containers outside and let the clothes hang and air out for a day before wearing. Adolescents have recently been found to use mothballs for huffing.[1][2] Mothballs have also been found to be a carcinogen (i.e. a cancer-causing agent). # Other uses Mothballs can also be used as a snake repellent. Mothballs (or sulfur) is usually used along with the aid of naphtha for these purposes. When mixed together, the snake sampling the air senses its acrid stench and its scent sampling is overloaded by the stench. It can't sense prey or danger as well with this smell, so it turns away. Put the mothballs around the perimeter of your yard leaving an "escape" for the snakes to get away or they will be locked in your yard. Caution should be exercised, as mothballs are not child or pet friendly and they can kill some types of plants. Rain or water will disintegrate the mothballs, so frequent reapplication will be necessary.	https://www.wikidoc.org/index.php/Mothball
6bf81bda63973c6916eff46d99c2ec5c352b0210	wikidoc	Mourning	Mourning # Overview Mourning is, in the simplest sense, synonymous with grief over the death of someone. The word is also used to describe a cultural complex of behaviours in which the bereaved participate or are expected to participate. Customs vary between different cultures and evolve over time, though many core behaviors remain constant. Wearing dark, sombre clothes is one practice followed in many countries, though other forms of dress are also seen. Those most affected by the loss of a loved one often observe a period of grieving, marked by withdrawal from social events and quiet, respectful behavior. People may also follow certain religious traditions for such occasions. Mourning may also apply to the death of, or anniversary of the passing of, an important individual like a local leader, monarch, religious figure etc. State mourning may occur on such an occasion. In recent years some traditions have given way to less strict practices, though many customs and traditions continue to be followed. # Social customs and dress ## Continental Europe The custom of wearing unadorned black clothing for mourning dates back at least to the Roman Empire, when the Toga pulla made of dark-colored wool was worn during periods of mourning. Through the Middle Ages and Renaissance, distinctive mourning was worn for general as well as personal loss; after the St. Bartholomew's Day Massacre of Huguenots in France, Elizabeth I of England and her court are said to have dressed in full mourning to receive the French Ambassador. Women in mourning and widows wore distinctive black caps and veils, generally in a conservative version of the current fashion. In rural areas of Mexico, Portugal, Spain, Italy and Greece widows will wear black for the rest of their lives. The immediate family members of the deceased will wear black for an extended period of time. ### White mourning The colour of deepest mourning among medieval European queens was white rather than black. This tradition survived in Spain until the end of the fifteenth century, and was again practiced by the Spanish-born Belgian Queen Fabiola of King Baudouin's funeral. It was the custom for the Queens of France to wear deuil blanc or "white mourning"; this is the origin of the white wardrobe created by Norman Hartnell for Queen Elizabeth, later the Queen Mother, in 1938, when Elizabeth was required to make a state visit to France while in mourning for her mother. ## United Kingdom Nowadays there is no special dress or behaviour required for those in mourning and even the wearing of black at funerals is in decline. Traditionally however there were strict social rules to be observed. By the 19th century, mourning behaviour in England had developed into a complex set of rules, particularly among the upper classes. Women bore the greatest burden of these customs. They involved wearing heavy, concealing, black clothing, and the use of heavy veils of black crêpe. The entire ensemble was colloquially known as widow's weeds (from the Old English "Waed" meaning "garment"). Advertisement for Victorian mourning garb Special caps and bonnets, usually in black or other dark colours, went with these ensembles. There was even special mourning jewellery, often made of jet or the hair of the deceased. The wealthy could also wear cameos or lockets designed to hold a lock of the deceased's hair or some similar relic. Widows were expected to wear special clothes to indicate that they were in mourning for up to four years after the death. To remove the costume earlier was thought disrespectful to the decedent, and if the widow was still young and attractive, suggestive of potential sexual promiscuity. Those subject to the rules were slowly allowed to re-introduce conventional clothing at different time periods; stages were known by such terms as "full mourning", "half mourning", and similar descriptions. Friends, acquaintances, and employees wore mourning to a greater or lesser degree depending on their relationship with the deceased. In general, servants wore black armbands when there had been a death in the household. Mourning was worn for six months for a sibling. Parents would wear mourning for, "as long as they feel so disposed." A widow was supposed to wear mourning for two years and was not supposed to enter society for twelve months. No lady or gentleman in mourning was supposed to attend balls. Amongst polite company the wearing of simply a black arm band was seen as appropriate only for military men (or others compelled to wear uniform in the course of their duties); wearing a black arm band instead of proper mourning clothes was seen as a degradation of proper ettiquette and to be avoided. Formal mourning culminated during the reign of Queen Victoria. Victoria herself may have had much to do with the practice, owing to her long and conspicuous grief over the death of her husband, Prince Albert. Although fashions began to be more functional and less restrictive for the succeeding Edwardians, appropriate dress for men and women, including that for the period of mourning, was still strictly prescribed and rigidly adhered to. The rules were gradually relaxed and acceptable practice for both sexes became to dress in dark colours for up to a year after a death in the family. By the late 20th century, this no longer applied. ## United States Mourning generally followed English forms. In the antebellum South, with social mores that rivaled those of England, mourning was just as strictly observed. The sequence in the book and film of Gone with the Wind in which Scarlett O’Hara scandalizes the attendees at a ball by accepting Rhett Butler’s invitation to dance, despite the fact that she is in mourning for her late husband, accurately reflects the social customs of the time. Victorian mourning could be quite expensive. At the end of The Wonderful Wizard of Oz, Dorothy explains to Glinda that she must return home because her aunt and uncle can not afford to go into mourning for her. The loss of the male head of the family had serious ramifications for American Indian widows; mourning among some tribes included the act of cutting off of a finger. ## Africa Bark cloth, a rough traditional fabric, was worn in some communities to denote that family members were in mourning. White garments are also used; following the advent of Christianity, black garments were worn, following European custom. ### Ethiopia In Ethiopia, an edir is a traditional community organization in which the members assist each other during the mourning process. Members make monthly financial contributions forming the Edir's fund and they will be entitled to receive a certain sum of money from this fund, the rate of which varies based on how close the deceased is to the Edir member. The purpose for such payment is to help cover the funeral and other expenses associated with the death. In addition, female members of the Edir take turns to do the house work like preparing food for the mourning family and people coming to comfort them. Usually, the male members take the responsibility to arrange the funeral, erect a temporary tent to shelter guests who come to visit the mourning family. Edir members are also required to stay with the mourning family and comfort them for three full days. # State & Official mourning State mourning, or in the case of monarchies, court mourning, refers to displays of mourning behavior on the death of a public figure or member of a royal family. The degree and duration of public mourning is generally decreed by a protocol officer. It was not unusual for the British court to declare that all citizens should wear full mourning for a specified period after the death of the monarch, or that the members of the court should wear full- or half-mourning for an extended period. On the death of Queen Victoria, (January 22, 1901), the Canada Gazette published an "extra" edition announcing that court mourning would continue until January 24, 1902, and directing the public to wear deep mourning until March 6, 1901, and half-mourning until April 17, 1901. The black-and-white costumes designed by Cecil Beaton for the Royal Ascot sequence in My Fair Lady were inspired by the "Black Ascot" of 1910, when the court was in mourning for Victoria's son, Edward VII. All over the world, states usually declare a period of official mourning after the death of a Head of state. The signs may vary but usually include the lowering or posting half-staff of flags on public buildings. In contrast, in the United Kingdom, the Royal Standard is never flown at half-mast, because there is always a monarch on the throne. On the death of the Emir of Kuwait in January 2006, a 40-day mourning period was declared. On Tonga, the official mourning lasts for a year; only afterwards is the royal heir crowned the new king. On the other hand, the principle of continuity of the state must be respected. The principle is reflected in the French saying "Le Roi est mort, vive le Roi!" ("The king is dead, long live the king!"). Regardless of the formalities of mourning, power must be handed on; if the succession is uncontested, that is best done immediately. Yet a short interruption of work in the civil service may result from one or more days of closing the offices, especially on the day of the state funeral. # Religions and Customs ## Christianity The European social forms described above are, in general, forms of Christian religious expression transferred to the greater community. In the Roman Catholic Church, the Mass of Paul VI, adopted in 1969, allows several options for the liturgical color used in Masses for the Dead. Prior to the liturgical reform, black was the ordinary color for funeral Masses; in the revised use, several options are available. According to the General Instruction of the Roman Missal (§346d-e), violet, white, or black vestments may be worn at Offices and Masses for the dead. Christian Churches often go into mourning symbolically during the period of Lent to commemorate the sacrifice and death of Jesus. Customs vary among the denominations and include the covering or removal of statuary, icons and paintings, and use of special liturgical colours, such as violet/purple, during Lent and Holy Week. In more formal congregations, parishioners also dress according to specific forms during Holy Week, particularly on Maundy Thursday and Good Friday, where it is still common to wear black or sombre dress or, as mentioned, the liturgical color purple. ## Hinduism Death is not seen as the final "end", but is seen as a turning point in the seemingly endless journey of the indestructible "atman" or the soul through innumerable bodies of animals and people. Hence Hinduism, prohibits excessive mourning or lamentation upon death, as this can hinder the easy passage of the departed soul towards its journey ahead: "As mourners will not help the dead in this world, therefore (the relatives) should not weep, but perform the obsequies to the best of their power." Hindu mourning is described in dharma shastras. It begins immediately after the cremation of the body and ends on the morning of the thirteenth day. Traditionally the body is cremated within 24 hours after death, however the cremations are not held after sunset and before sunrise. Immediately after the death an oil lamp is lit near the deceased and this lamp is kept burning for three days. Hinduism associates death with ritual impurity for the immediate blood family of the deceased, hence during these mourning days, the immediate blood family must not perform any religious ceremonies (except funerals), must not visit temples or other sacred places, must not serve the sages (holy men), must not give alms, must not read or recite from the sacred scriptures nor can they attend social functions like marriages, parties etc. Hence the family of the deceased is not expected to serve any visiting guests food or drink, and it is customary that the visiting guests do not eat or drink in the house where the death has occurred. The family in mourning are required to bathe twice a day, eat a single simple vegetarian meal and try to cope up with their loss. On the day on which the death has occurred, the family do not cook, hence usually close family and friends will provide food for the mourning family. White clothing (the colour of purity) is also the colour of mourning and many will wear white during the mourning period. On the morning of the thirteenth day, a Shraddha ceremony is performed. The main ceremony involves a fire sacrifice, in which offerings are given to the ancestors and to gods, to ensure the deceased has a peaceful afterlife. Typically after the ceremony, the family cleans and washes all the idols in the family shrine and flowers, fruits, water and purified food is offered to the gods. Now the family is ready to break the period of mourning and return back to daily life. ## Islam Mourning is observed in Islam by increased devotion, receiving visitors and condolences, and avoiding decorative clothing and jewelry. Loved ones and relatives are to observe a 3-day mourning period. Widows observe an extended mourning period (Iddah), 4 months and 10 days long, in accordance with the Qur'an 2:234. During this time, she is not to remarry, move from her home, or wear decorative clothing or jewelry. Grief at the death of a beloved person is normal, and weeping for the dead is allowed in Islam. What is prohibited is to express grief by wailing ( Bewailing refers to mourning in a loud voice), shrieking, beating the chest and cheeks, tearing hair or clothes, breaking things or scratching faces or saying phrases that makes a Muslim lose faith. Qur'an prohibits widows to engage themselves for four lunar months and ten days, after the death of their husbands. According to Qur'an: Islamic scholars consider this directive a balance between mourning a husband's death and protection of the widow from censure that she became interested in re-marrying too soon after her husband’s death. This is also to ascertain whether or not a lady is pregnant. ## Judaism Judaism looks upon mourning as a process by which the stricken can re-enter into society, and so provides a series of customs that make this process. The most known and central stage is Shiva, which is a Jewish mourning practice in which people adjust their behaviour as an expression of their bereavement for the week immediately after the burial. In the West, typically, mirrors are covered and a small tear is made in an item of clothing to indicate a lack of interest in personal vanity. The bereaved dress simply and sit on the floor, short stools or boxes rather than chairs when receiving the condolences of visitors. English speakers use the expression "to sit shiva". # Modern customs Mourning attire became less customary after the mid-twentieth century, by which time it had already been determined that mourning was not to be worn in the business arena. It is still customary, though not as universal, to indicate mourning through somber, semi-formal dress, particularly at the funeral and among the family and close friends of the deceased. As such, men often wear a suit and tie, while a woman may wear a dark-colored, long-sleeved dress or pantsuit. The armband is still seen, but mostly amongst Irish, German, Austrian, and other northern- and central-European Catholic groups such as the Ancient Order of Hibernians. A few modern customs have evolved, for example the use of sunglasses in order to hide tear-swollen eyes. Mourning is used as a statement of respect, solidarity, commemoration, or protest by a particular group in an unusual circumstance. For instance: - The wearing of black armbands by the Israeli Olympic team in 1976 to commemorate the attack on the team during the 1972 Olympic Games. - A sports team may wear black armbands, or affix a black stripe to their uniforms, for a specified time period following the death of an owner, coach, teammate or (if the decedent is a high school student), classmate. - A community wearing special-colored ribbons on a designated day or for a particular time period. For instance, the wearing of red, white and blue following the September 11th attacks. - Observing a "moment of silence" and/or flying flags at half-staff following a death. This most frequently happens in conjunction with national periods of mourning (such as the death of a former or current Head of State or other notable leader). - However, flags are sometimes lowered to half-staff in other circumstances, such as after the death of a high school student or noted local figure; such circumstances vary widely and are usually influenced by local customs. - In all cases, when a flag is to be flown at half-staff or half-mast it is first to be fully hoisted and only then lowered half-way, never raised only to half-way and left there. - Local-, state- and federal-uniformed employees who wear badges place a black band around the badge when a fellow employee has been killed in the line of duty. - The wearing of a black armband to protest an action by one's government that the wearer considers so atrocious as to warrant mourning for the loss of the decency/respect for human life/morals of their country. A circumstance in which this would occur would be a time when a person believes that their country has committed genocide, or made a decision that will jeopardize the future of their country. - A wedding ring, either the original or the dead partner's, may be worn for a period after the death.	Mourning Template:Wiktionarypar # Overview Mourning is, in the simplest sense, synonymous with grief over the death of someone. The word is also used to describe a cultural complex of behaviours in which the bereaved participate or are expected to participate. Customs vary between different cultures and evolve over time, though many core behaviors remain constant. Wearing dark, sombre clothes is one practice followed in many countries, though other forms of dress are also seen. Those most affected by the loss of a loved one often observe a period of grieving, marked by withdrawal from social events and quiet, respectful behavior. People may also follow certain religious traditions for such occasions. Mourning may also apply to the death of, or anniversary of the passing of, an important individual like a local leader, monarch, religious figure etc. State mourning may occur on such an occasion. In recent years some traditions have given way to less strict practices, though many customs and traditions continue to be followed. # Social customs and dress ## Continental Europe The custom of wearing unadorned black clothing for mourning dates back at least to the Roman Empire, when the Toga pulla made of dark-colored wool was worn during periods of mourning. Through the Middle Ages and Renaissance, distinctive mourning was worn for general as well as personal loss; after the St. Bartholomew's Day Massacre of Huguenots in France, Elizabeth I of England and her court are said to have dressed in full mourning to receive the French Ambassador. Women in mourning and widows wore distinctive black caps and veils, generally in a conservative version of the current fashion. In rural areas of Mexico, Portugal, Spain, Italy and Greece widows will wear black for the rest of their lives. The immediate family members of the deceased will wear black for an extended period of time. ### White mourning The colour of deepest mourning among medieval European queens was white rather than black. This tradition survived in Spain until the end of the fifteenth century, and was again practiced by the Spanish-born Belgian Queen Fabiola of King Baudouin's funeral. It was the custom for the Queens of France to wear deuil blanc or "white mourning"; this is the origin of the white wardrobe created by Norman Hartnell for Queen Elizabeth, later the Queen Mother, in 1938, when Elizabeth was required to make a state visit to France while in mourning for her mother. ## United Kingdom Nowadays there is no special dress or behaviour required for those in mourning and even the wearing of black at funerals is in decline. Traditionally however there were strict social rules to be observed. By the 19th century, mourning behaviour in England had developed into a complex set of rules, particularly among the upper classes. Women bore the greatest burden of these customs. They involved wearing heavy, concealing, black clothing, and the use of heavy veils of black crêpe. The entire ensemble was colloquially known as widow's weeds (from the Old English "Waed" meaning "garment"). Advertisement for Victorian mourning garb Special caps and bonnets, usually in black or other dark colours, went with these ensembles. There was even special mourning jewellery, often made of jet or the hair of the deceased. The wealthy could also wear cameos or lockets designed to hold a lock of the deceased's hair or some similar relic. Widows were expected to wear special clothes to indicate that they were in mourning for up to four years after the death. To remove the costume earlier was thought disrespectful to the decedent, and if the widow was still young and attractive, suggestive of potential sexual promiscuity. Those subject to the rules were slowly allowed to re-introduce conventional clothing at different time periods; stages were known by such terms as "full mourning", "half mourning", and similar descriptions. Friends, acquaintances, and employees wore mourning to a greater or lesser degree depending on their relationship with the deceased. In general, servants wore black armbands when there had been a death in the household. Mourning was worn for six months for a sibling. Parents would wear mourning for, "as long as they feel so disposed." A widow was supposed to wear mourning for two years and was not supposed to enter society for twelve months. No lady or gentleman in mourning was supposed to attend balls. Amongst polite company the wearing of simply a black arm band was seen as appropriate only for military men (or others compelled to wear uniform in the course of their duties); wearing a black arm band instead of proper mourning clothes was seen as a degradation of proper ettiquette and to be avoided.[1] Formal mourning culminated during the reign of Queen Victoria. Victoria herself may have had much to do with the practice, owing to her long and conspicuous grief over the death of her husband, Prince Albert. Although fashions began to be more functional and less restrictive for the succeeding Edwardians, appropriate dress for men and women, including that for the period of mourning, was still strictly prescribed and rigidly adhered to. The rules were gradually relaxed and acceptable practice for both sexes became to dress in dark colours for up to a year after a death in the family. By the late 20th century, this no longer applied. ## United States Mourning generally followed English forms. In the antebellum South, with social mores that rivaled those of England, mourning was just as strictly observed. The sequence in the book and film of Gone with the Wind in which Scarlett O’Hara scandalizes the attendees at a ball by accepting Rhett Butler’s invitation to dance, despite the fact that she is in mourning for her late husband, accurately reflects the social customs of the time. Victorian mourning could be quite expensive. At the end of The Wonderful Wizard of Oz, Dorothy explains to Glinda that she must return home because her aunt and uncle can not afford to go into mourning for her.[2] The loss of the male head of the family had serious ramifications for American Indian widows; mourning among some tribes included the act of cutting off of a finger.[citation needed] ## Africa Template:Expand-section Bark cloth, a rough traditional fabric, was worn in some communities to denote that family members were in mourning.[citation needed] White garments are also used; following the advent of Christianity, black garments were worn, following European custom.[citation needed] ### Ethiopia In Ethiopia, an edir is a traditional community organization in which the members assist each other during the mourning process. Members make monthly financial contributions forming the Edir's fund and they will be entitled to receive a certain sum of money from this fund, the rate of which varies based on how close the deceased is to the Edir member. The purpose for such payment is to help cover the funeral and other expenses associated with the death. In addition, female members of the Edir take turns to do the house work like preparing food for the mourning family and people coming to comfort them. Usually, the male members take the responsibility to arrange the funeral, erect a temporary tent to shelter guests who come to visit the mourning family. Edir members are also required to stay with the mourning family and comfort them for three full days. # State & Official mourning State mourning, or in the case of monarchies, court mourning, refers to displays of mourning behavior on the death of a public figure or member of a royal family. The degree and duration of public mourning is generally decreed by a protocol officer. It was not unusual for the British court to declare that all citizens should wear full mourning for a specified period after the death of the monarch, or that the members of the court should wear full- or half-mourning for an extended period. On the death of Queen Victoria, (January 22, 1901), the Canada Gazette published an "extra" edition announcing that court mourning would continue until January 24, 1902, and directing the public to wear deep mourning until March 6, 1901, and half-mourning until April 17, 1901. The black-and-white costumes designed by Cecil Beaton for the Royal Ascot sequence in My Fair Lady were inspired by the "Black Ascot" of 1910, when the court was in mourning for Victoria's son, Edward VII. All over the world, states usually declare a period of official mourning after the death of a Head of state. The signs may vary but usually include the lowering or posting half-staff of flags on public buildings. In contrast, in the United Kingdom, the Royal Standard is never flown at half-mast, because there is always a monarch on the throne. On the death of the Emir of Kuwait in January 2006, a 40-day mourning period was declared. On Tonga, the official mourning lasts for a year; only afterwards is the royal heir crowned the new king. On the other hand, the principle of continuity of the state must be respected. The principle is reflected in the French saying "Le Roi est mort, vive le Roi!" ("The king is dead, long live the king!"). Regardless of the formalities of mourning, power must be handed on; if the succession is uncontested, that is best done immediately. Yet a short interruption of work in the civil service may result from one or more days of closing the offices, especially on the day of the state funeral. # Religions and Customs ## Christianity The European social forms described above are, in general, forms of Christian religious expression transferred to the greater community. In the Roman Catholic Church, the Mass of Paul VI, adopted in 1969, allows several options for the liturgical color used in Masses for the Dead. Prior to the liturgical reform, black was the ordinary color for funeral Masses; in the revised use, several options are available. According to the General Instruction of the Roman Missal (§346d-e), violet, white, or black vestments may be worn at Offices and Masses for the dead. Christian Churches often go into mourning symbolically during the period of Lent to commemorate the sacrifice and death of Jesus. Customs vary among the denominations and include the covering or removal of statuary, icons and paintings, and use of special liturgical colours, such as violet/purple, during Lent and Holy Week. In more formal congregations, parishioners also dress according to specific forms during Holy Week, particularly on Maundy Thursday and Good Friday, where it is still common to wear black or sombre dress or, as mentioned, the liturgical color purple. ## Hinduism Death is not seen as the final "end", but is seen as a turning point in the seemingly endless journey of the indestructible "atman" or the soul through innumerable bodies of animals and people. Hence Hinduism, prohibits excessive mourning or lamentation upon death, as this can hinder the easy passage of the departed soul towards its journey ahead: "As mourners will not help the dead in this world, therefore (the relatives) should not weep, but perform the obsequies to the best of their power."[3] Hindu mourning is described in dharma shastras[4][5]. It begins immediately after the cremation of the body and ends on the morning of the thirteenth day. Traditionally the body is cremated within 24 hours after death, however the cremations are not held after sunset and before sunrise. Immediately after the death an oil lamp is lit near the deceased and this lamp is kept burning for three days. Hinduism associates death with ritual impurity for the immediate blood family of the deceased, hence during these mourning days, the immediate blood family must not perform any religious ceremonies (except funerals), must not visit temples or other sacred places, must not serve the sages (holy men), must not give alms, must not read or recite from the sacred scriptures nor can they attend social functions like marriages, parties etc. Hence the family of the deceased is not expected to serve any visiting guests food or drink, and it is customary that the visiting guests do not eat or drink in the house where the death has occurred. The family in mourning are required to bathe twice a day, eat a single simple vegetarian meal and try to cope up with their loss. On the day on which the death has occurred, the family do not cook, hence usually close family and friends will provide food for the mourning family. White clothing (the colour of purity) is also the colour of mourning and many will wear white during the mourning period. On the morning of the thirteenth day, a Shraddha ceremony is performed. The main ceremony involves a fire sacrifice, in which offerings are given to the ancestors and to gods, to ensure the deceased has a peaceful afterlife. Typically after the ceremony, the family cleans and washes all the idols in the family shrine and flowers, fruits, water and purified food is offered to the gods. Now the family is ready to break the period of mourning and return back to daily life. ## Islam Mourning is observed in Islam by increased devotion, receiving visitors and condolences, and avoiding decorative clothing and jewelry. Loved ones and relatives are to observe a 3-day mourning period.[6] Widows observe an extended mourning period (Iddah), 4 months and 10 days[7] long, in accordance with the Qur'an 2:234. During this time, she is not to remarry, move from her home, or wear decorative clothing or jewelry. Grief at the death of a beloved person is normal, and weeping for the dead is allowed in Islam.[8] What is prohibited is to express grief by wailing ( Bewailing refers to mourning in a loud voice), shrieking, beating the chest and cheeks, tearing hair or clothes, breaking things or scratching faces or saying phrases that makes a Muslim lose faith.[9] Qur'an prohibits widows to engage themselves for four lunar months and ten days, after the death of their husbands. According to Qur'an: Template:Cquotetxt Islamic scholars consider this directive a balance between mourning a husband's death and protection of the widow from censure that she became interested in re-marrying too soon after her husband’s death.[10] This is also to ascertain whether or not a lady is pregnant.[11] ## Judaism Judaism looks upon mourning as a process by which the stricken can re-enter into society, and so provides a series of customs that make this process. The most known and central stage is Shiva, which is a Jewish mourning practice in which people adjust their behaviour as an expression of their bereavement for the week immediately after the burial. In the West, typically, mirrors are covered and a small tear is made in an item of clothing to indicate a lack of interest in personal vanity. The bereaved dress simply and sit on the floor, short stools or boxes rather than chairs when receiving the condolences of visitors. English speakers use the expression "to sit shiva". # Modern customs Mourning attire became less customary after the mid-twentieth century, by which time it had already been determined that mourning was not to be worn in the business arena. It is still customary, though not as universal, to indicate mourning through somber, semi-formal dress, particularly at the funeral and among the family and close friends of the deceased. As such, men often wear a suit and tie, while a woman may wear a dark-colored, long-sleeved dress or pantsuit. The armband is still seen, but mostly amongst Irish, German, Austrian, and other northern- and central-European Catholic groups such as the Ancient Order of Hibernians. A few modern customs have evolved, for example the use of sunglasses in order to hide tear-swollen eyes. Mourning is used as a statement of respect, solidarity, commemoration, or protest by a particular group in an unusual circumstance. For instance: - The wearing of black armbands by the Israeli Olympic team in 1976 to commemorate the attack on the team during the 1972 Olympic Games. - A sports team may wear black armbands, or affix a black stripe to their uniforms, for a specified time period following the death of an owner, coach, teammate or (if the decedent is a high school student), classmate. - A community wearing special-colored ribbons on a designated day or for a particular time period. For instance, the wearing of red, white and blue following the September 11th attacks. - Observing a "moment of silence" and/or flying flags at half-staff following a death. This most frequently happens in conjunction with national periods of mourning (such as the death of a former or current Head of State or other notable leader). - However, flags are sometimes lowered to half-staff in other circumstances, such as after the death of a high school student or noted local figure; such circumstances vary widely and are usually influenced by local customs. - In all cases, when a flag is to be flown at half-staff or half-mast it is first to be fully hoisted and only then lowered half-way, never raised only to half-way and left there. - Local-, state- and federal-uniformed employees who wear badges place a black band around the badge when a fellow employee has been killed in the line of duty. - The wearing of a black armband to protest an action by one's government that the wearer considers so atrocious as to warrant mourning for the loss of the decency/respect for human life/morals of their country. A circumstance in which this would occur would be a time when a person believes that their country has committed genocide, or made a decision that will jeopardize the future of their country.[citation needed] - A wedding ring, either the original or the dead partner's, may be worn for a period after the death.	https://www.wikidoc.org/index.php/Mourning
5fad85fb7e6ceb0c82d2cb66db78a46c60e209f3	wikidoc	Mucocele	Mucocele Synonyms and keywords: Mucus extravasation phenomenon. # Overview A mucocele, also referred to as mucus extravasation phenomenon, is a swelling of connective tissue consisting of collected mucin from a ruptured salivary gland duct, which is usually caused by local trauma. The mucocele is a bluish translucent color, and is more commonly found in children and young adults. # Locations The most common location to find a mucocele is the surface of the lower lip. It can also be found on the inner side of the cheek (known as the buccal mucosa), on the anterior ventral tongue, and the floor of the mouth. When found on the floor of the mouth, the mucocele is referred to as a ranula. They are rarely found on the upper lip. # Characteristics The size of mucoceles vary from 1 mm to several centimeters. On palpation, mucoceles may appear to fluctuant but can also be firm. Their duration lasts from days to years, and may have recurrent swelling with occasional rupturing of its contents. # Variations A variant of a mucocele is found on the palate, retromolar pad, and posterior buccal mucosa. Known as a "superficial mucocele", this type presents as single or multiple vesicles and bursts into an ulcer. Despite healing after a few days, superficial mucoceles recur often in the same location. # Histology Microscopically, mucoceles appears as granulation tissue surrounding mucin. Since inflammation occurs concurrently, neutrophils and foamy histiocytes usually are present. # Physical examination ## Gallery ### Skin - url = > - url = > - url = > - url = > - url = > - url = > # Treatment Some mucoceles spontaneously resolve on their own after a short time. Others are chronic and require surgical removal. Recurrence may occur, and thus the adjacent salivary gland is excised as a preventive measure. Several types of procedures are available for the surgical removal of mucoceles. These include laser and minimally-invasive techniques which means recovery times are reduced drastically.	Mucocele Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]. Synonyms and keywords: Mucus extravasation phenomenon. # Overview A mucocele, also referred to as mucus extravasation phenomenon, is a swelling of connective tissue consisting of collected mucin from a ruptured salivary gland duct, which is usually caused by local trauma. The mucocele is a bluish translucent color, and is more commonly found in children and young adults. # Locations The most common location to find a mucocele is the surface of the lower lip. It can also be found on the inner side of the cheek (known as the buccal mucosa), on the anterior ventral tongue, and the floor of the mouth. When found on the floor of the mouth, the mucocele is referred to as a ranula. They are rarely found on the upper lip. # Characteristics The size of mucoceles vary from 1 mm to several centimeters. On palpation, mucoceles may appear to fluctuant but can also be firm. Their duration lasts from days to years, and may have recurrent swelling with occasional rupturing of its contents. # Variations A variant of a mucocele is found on the palate, retromolar pad, and posterior buccal mucosa. Known as a "superficial mucocele", this type presents as single or multiple vesicles and bursts into an ulcer. Despite healing after a few days, superficial mucoceles recur often in the same location. # Histology Microscopically, mucoceles appears as granulation tissue surrounding mucin. Since inflammation occurs concurrently, neutrophils and foamy histiocytes usually are present. # Physical examination ## Gallery ### Skin - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=305> # Treatment Some mucoceles spontaneously resolve on their own after a short time. Others are chronic and require surgical removal. Recurrence may occur, and thus the adjacent salivary gland is excised as a preventive measure. Several types of procedures are available for the surgical removal of mucoceles. These include laser and minimally-invasive techniques which means recovery times are reduced drastically.	https://www.wikidoc.org/index.php/Mucocele
204b2bd50a5e48cbf23d9affb9b31bd2e7db3685	wikidoc	Mushroom	Mushroom A Mushroom is the fleshy, spore-bearing fruiting body of fungus typically produced above ground on soil or on their food source. The standard for the name mushroom is the cultivated white button mushroom, Agaricus bisporus, hence the word mushroom is most often applied to fungi (Basidiomycota, Agaricomycetes) that have a stem (called a stipe), a cap (called a pileus), and gills (each called a lamella/pl. lamellae) on the underside of the cap just as do store-bought white mushrooms. However, mushrooms can also be a wide variety of gilled fungi, with or without stems, and the term is used even more generally to describe both fleshy fruitbodies of some Ascomycota and woody or leathery fruitbodies of some Basidiomycota, depending upon the context of the usage. Usually forms deviating from the standard form have more specific names, such as puffballs, stinkhorn, morels, etc. and gilled mushrooms themselves are often called agarics, in reference to their similarity to Agaricus or placement in the order Agaricales. By extension, mushroom can also designate the entire fungus when in culture or when referring to the whole thallus (called a mycelium) of species forming fruitbodies called mushrooms. # Identification Identifying mushrooms requires a basic understanding of their macroscopic structure. Most are Basidiomycetes and gilled. Their spores, called basidiospores, are produced on the gills and fall in a fine rain of powder from under the caps as a result. At the microscopic level the basidiospores are shot off of basidia but then fall between the gills in the dead air space. As a result, for most mushrooms, if the cap is cut off and placed gill-side down, usually overnight a powdery impression reflecting the shape of the gills (or pores, or spines, etc.) is formed (when the fruitbody is sporulating). The color of the powdery print (which is called a spore print) has been used to help classify mushrooms, hence is used to help identify them. Spore print colors range from white (most common), brown, black, purple-brown, pink, yellow, cream, and almost never blue, green, or red. While modern identification of mushrooms is quickly becoming molecular, the standard methods for identification are still used by most and have developed into a fine art harking back to mediaeval times and the Victorian era, combined with microscopic examination. The presence of juices upon breaking, bruising reactions, odors, tastes, shades of colors, and habitats and habit and season must, and are, all considered by mycologists, amateur and professional alike. Tasting and smelling mushrooms carry their own hazards because of poisons and allergens. Chemical spot tests are also used for some genera. In general, identification to genus can often be accomplished in the field using a local mushroom guide. Identification to species, however, requires more effort; one must remember that a mushroom develops from a button stage into a mature structure and only the latter can provide certain characters needed for the identification of the species. However, over mature specimens lose features and cease producing spores. Many novices have mistaken humid water marks on paper for white spore prints, or discolored paper from oozing liquids on lamella edges for colored spored prints. # Classification Typical mushrooms are the fruitbodies of members of the order Agaricales, whose type genus is Agaricus, and type species is the field mushroom, Agaricus campestris. However, in modern molecular defined classifications, not all members of the order Agaricales produce mushroom fruitbodies, and many other gilled fungi, collectively called mushrooms, occur in other orders in the class Agaricomycetes. For example, chanterelles are in the Cantharellales, false chanterelles like Gomphus are in the Gomphales, milk mushrooms (Lactarius) and russulas (Russula) as well as Lentinellus are in the Russulales, while the tough leathery genera Lentinus and Panus are among the Polyporales, but Neolentinus is in the Gloeophyllales, and the little pin-mushroom genus, Rickenella along with similar genera are in the Hymenochaetales. Within the main body of mushrooms, in the Agaricales, are such common fungi like the common fairy-ring mushroom (Marasmius oreades), shiitake, enoki, oyster mushrooms, fly agarics and other amanitas, magic mushrooms like species of Psilocybe, paddy straw mushrooms, shaggy manes, etc. An atypical 'mushroom' is the Lobster mushroom, which is a deformed, cooked-lobster-colored parasitized fruitbody of a Russula or Lactarius colored and deformed by the mycoparasitic Ascomycete Hypomyces lactifluorum. Other 'mushrooms' are nongilled and then the term is loosely used, so that it is difficult to give a full account of their classifications. Some 'mushrooms' have pores underneath (and are usually called boletes), others have spines, such as the hedgehog mushroom and other tooth fungi, and so on. Mushroom has been used for polypores, puffballs, jelly fungi, coral fungi, bracket fungi, stinkhorns, and cup fungi. Mushrooms and other fungi are studied by mycologists. Thus, the term mushroom is more one of common application to macroscopic fungal fruiting bodies than one having precise taxonomic meaning. There are approximately 14,000 described species of mushrooms. # Mushrooms vs. Toadstools The terms "mushrooms" and "toadstools" go back centuries, and were never precisely defined, nor was there consensus on application. The term "toadstool" was often but not exclusively, applied to poisonous mushrooms or to those that have the classic umbrella-like cap-and-stem form. For an example of early usage see Badham (1863). Reference was made to "tadstoles", "frogstooles", "frogge stoles", "tadstooles", "tode stoles", "toodys hatte","paddockstool", "puddockstool", "paddocstol", "toadstoole", and "paddockstooles" from 1398-1597, sometimes synonymous with "mushrom", "mushrum", "muscheron", "mousheroms", "mussheron", or "musserouns" . The term "mushroom" and its variations may have been derived from the French word "Mousseron" in reference to moss (mousse). There may have been a direct connection to toads (in reference to poisonous properties) for toadstools. However, there is no clear-cut delimitation between edible and poisonous fungi, so that mushrooms may be edible, poisonous, or unpalatable, and it makes no sense to not be able to use the term mushroom when stating there are "poisonous mushrooms" which would be an oxymoron if the term mushroom could not be applied to poisonous fungi. The term toadstool is nowadays used in story telling when referring to poisonous or suspect mushrooms, and mycologists avoid the use of the term as it is highly ambiguous. The classic example of a toadstool is Amanita muscaria. # To mushroom - mushrooming - to pop up like mushrooms Many species of mushrooms seemingly appear overnight, growing or expanding rapidly. This phenomenon is the source of several commonly used phrases in the English language. In fact all species of mushrooms take several days to form primordial mushroom fruit bodies. The cultivated mushroom as well as the common field mushroom initially form minute fruiting body initials referred to as the pin stage, because of their small size. Slightly expanded they are called buttons, once again because of the relative size and shape. Once such stages are formed, the mushroom can rapidly pull in water from its mycelium and expand, mainly by inflating preformed cells that took several days to form in the primordia. Similarly, there are even more ephemeral mushrooms, like Parasola plicatilis ( formerly Coprinus plicatlis) that literally appear overnight and may be gone by late afternoon on hot summer days after rainfall. The primordia form at ground level in lawns in humid spaces under the thatch of lawns and after heavy rainfall or dewy conditions, balloon to full size in a few hours, release spores, then collapse. They "mushroom" to full size. "To mushroom" means to rapidly grow in size, or to sprout up rapidly, i.e., an organization may "mushroom" from national to international almost overnight. To "pop up like mushrooms" is of similar derivation, but also has a gang slang usage. The slang term "mushrooms" is a gang related term for victims accidentally shot as collateral damage simply because they popped up suddenly, as do fungal mushrooms. The term "mushrooming" differs in that it generally refers to the act of gathering mushrooms, in the wild, as in the statement "I'm going mushrooming today." This is often shortened to "shrooming", which has yet another connotation, which is to "do mushrooms". To "do mushrooms" or "shrooms" often refers to taking hallucinogenic mushrooms (see below). Notably, not all mushrooms expand overnight. Many are very slow growing. Those types of mushrooms generally add tissue to their fruitbodies in different manners, such as growing from the edges, or inserting hyphae. The largest living thing in the world is a mushroom. It is known as the honey fungus (Armillaria Ostoyae), and is not particularly a rare mushroom; you may well have one growing on a dead tree stump in your garden. The largest recorded specimen is in Malheur National Forest Oregon USA. It covers 2,200 acres and is between 2,000 and 8,000 years old. Most of it is underground in the form of white mycelia (the mushroom equivilant of roots). # Human use ## Edible mushrooms Edible mushrooms are used extensively in cooking, in many cuisines (notably Chinese, European and Japanese). Though commonly thought to contain little nutritional value, many species of mushrooms are high in fiber, and provide vitamins such as thiamine (B1), riboflavin (B2), niacin (B3), biotin (B7), cobalamins (B12) and ascorbic acid (C), as well as minerals, including iron, selenium, potassium and phosphorus. Mushrooms have been gaining a higher profile for containing antioxidants Ergothioneine and Selenium. Most mushrooms that are sold in supermarkets have been commercially grown on mushroom farms. The most popular of these, Agaricus bisporus, is safe for most people to eat because it is grown in controlled, sterilized environments, though some individuals do not tolerate it well. Several varieties of A. bisporus are grown commercially, including: whites, crimini and portabello. Other cultivated species now available at many grocers include shiitake, maitake or hen-of-the-woods, oyster and enoki. There are a number of species of mushrooms that are poisonous, and although some resemble certain edible species, eating them could be fatal. Eating mushrooms gathered in the wild can be risky and should not be undertaken by individuals not knowledgeable in mushroom identification, unless the individuals limit themselves to a relatively small number of good edible species that are visually distinctive. More generally, and particularly with gilled mushrooms, separating edible from poisonous species requires meticulous attention to detail: there is no single trait by which all toxic mushrooms could be identified, nor one by which all edible mushrooms could be identified. People who collect mushrooms for consumption are known as mycophagists, and the act of collecting them for such is known as mushroom hunting, or simply "mushrooming". ## Toxic mushrooms Of central interest with respect to chemical properties of mushrooms is the fact that many species produce secondary metabolites that render them toxic, mind-altering, or even bioluminescent. Toxicity likely plays a role in protecting the function of the basidiocarp: the mycelium has expended considerable energy and protoplasmic material to develop a structure to efficiently distribute its spores. One defense against consumption and premature destruction is the evolution of chemicals that render the mushroom inedible, either causing the consumer to vomit (see emetics) the meal or avoid consumption altogether. ## Psychoactive mushrooms Psilocybin mushrooms possess psychedelic properties. They are commonly known as "magic mushrooms" or "shrooms", and are available in smart shops in many parts of the world, though some countries have outlawed their sale. A number of other mushrooms are eaten for their psychoactive effects, such as fly agaric, which is used for shamanic purposes by tribes in northeast Siberia. They have also been used in the West to potentiate, or increase, religious experiences. Because of their psychoactive properties, some mushrooms have played a role in native medicine, where they have been used to affect mental and physical healing, and to facilitate visionary states. One such ritual is the Velada ceremony. A representative figure of traditional mushroom use is the shaman and curandera (priest-healer) María Sabina. ## Medicinal mushrooms Currently, many species of mushrooms and fungi utilized as folk medicines for thousands of years are under intense study by ethnobotanists and medical researchers. Maitake, shiitake, and reishi are prominent among those being researched for their potential anti-cancer, anti-viral, and/or immunity-enhancement properties. Psilocybin, originally an extract of certain psychedelic mushrooms, is being studied for its ability to help people suffering from mental disease, such as obsessive-compulsive disorder. Minute amounts have been reported to stop cluster and migraine headache . ## Other uses Mushrooms can be used for dyeing wool and other natural fibers. The chromophores of mushrooms are organic compounds and produce strong and vivid colors, and all colors of the spectrum can be achieved with mushroom dyes. Before the invention of synthetic dyes the mushrooms were the primary sources on dyeing textiles. This technique has survived in Finland, and many Middle Ages re-enactors have revived the skill again. Some fungi, types of polypores, loosely called mushrooms, have been used as fire starters (known as tinder fungi). Ötzi the Iceman was found carrying such fungi. Mushrooms, and other fungi, will likely play an increasingly important role in the development of effective biological remediation and filtration technologies. The US Patent and Trademark officecan be searched for patents related to the latest developments in mycoremediation and mycofiltration.	Mushroom A Mushroom is the fleshy, spore-bearing fruiting body of fungus typically produced above ground on soil or on their food source. The standard for the name mushroom is the cultivated white button mushroom, Agaricus bisporus, hence the word mushroom is most often applied to fungi (Basidiomycota, Agaricomycetes) that have a stem (called a stipe), a cap (called a pileus), and gills (each called a lamella/pl. lamellae) on the underside of the cap just as do store-bought white mushrooms. However, mushrooms can also be a wide variety of gilled fungi, with or without stems, and the term is used even more generally to describe both fleshy fruitbodies of some Ascomycota and woody or leathery fruitbodies of some Basidiomycota, depending upon the context of the usage. Usually forms deviating from the standard form have more specific names, such as puffballs, stinkhorn, morels, etc. and gilled mushrooms themselves are often called agarics, in reference to their similarity to Agaricus or placement in the order Agaricales. By extension, mushroom can also designate the entire fungus when in culture or when referring to the whole thallus (called a mycelium) of species forming fruitbodies called mushrooms. # Identification Identifying mushrooms requires a basic understanding of their macroscopic structure. Most are Basidiomycetes and gilled. Their spores, called basidiospores, are produced on the gills and fall in a fine rain of powder from under the caps as a result. At the microscopic level the basidiospores are shot off of basidia but then fall between the gills in the dead air space. As a result, for most mushrooms, if the cap is cut off and placed gill-side down, usually overnight a powdery impression reflecting the shape of the gills (or pores, or spines, etc.) is formed (when the fruitbody is sporulating). The color of the powdery print (which is called a spore print) has been used to help classify mushrooms, hence is used to help identify them. Spore print colors range from white (most common), brown, black, purple-brown, pink, yellow, cream, and almost never blue, green, or red. While modern identification of mushrooms is quickly becoming molecular, the standard methods for identification are still used by most and have developed into a fine art harking back to mediaeval times and the Victorian era, combined with microscopic examination. The presence of juices upon breaking, bruising reactions, odors, tastes, shades of colors, and habitats and habit and season must, and are, all considered by mycologists, amateur and professional alike. Tasting and smelling mushrooms carry their own hazards because of poisons and allergens. Chemical spot tests are also used for some genera. In general, identification to genus can often be accomplished in the field using a local mushroom guide. Identification to species, however, requires more effort; one must remember that a mushroom develops from a button stage into a mature structure and only the latter can provide certain characters needed for the identification of the species. However, over mature specimens lose features and cease producing spores. Many novices have mistaken humid water marks on paper for white spore prints, or discolored paper from oozing liquids on lamella edges for colored spored prints. # Classification Typical mushrooms are the fruitbodies of members of the order Agaricales, whose type genus is Agaricus, and type species is the field mushroom, Agaricus campestris. However, in modern molecular defined classifications, not all members of the order Agaricales produce mushroom fruitbodies, and many other gilled fungi, collectively called mushrooms, occur in other orders in the class Agaricomycetes. For example, chanterelles are in the Cantharellales, false chanterelles like Gomphus are in the Gomphales, milk mushrooms (Lactarius) and russulas (Russula) as well as Lentinellus are in the Russulales, while the tough leathery genera Lentinus and Panus are among the Polyporales, but Neolentinus is in the Gloeophyllales, and the little pin-mushroom genus, Rickenella along with similar genera are in the Hymenochaetales. Within the main body of mushrooms, in the Agaricales, are such common fungi like the common fairy-ring mushroom (Marasmius oreades), shiitake, enoki, oyster mushrooms, fly agarics and other amanitas, magic mushrooms like species of Psilocybe, paddy straw mushrooms, shaggy manes, etc. An atypical 'mushroom' is the Lobster mushroom, which is a deformed, cooked-lobster-colored parasitized fruitbody of a Russula or Lactarius colored and deformed by the mycoparasitic Ascomycete Hypomyces lactifluorum.[1] Other 'mushrooms' are nongilled and then the term is loosely used, so that it is difficult to give a full account of their classifications. Some 'mushrooms' have pores underneath (and are usually called boletes), others have spines, such as the hedgehog mushroom and other tooth fungi, and so on. Mushroom has been used for polypores, puffballs, jelly fungi, coral fungi, bracket fungi, stinkhorns, and cup fungi. Mushrooms and other fungi are studied by mycologists. Thus, the term mushroom is more one of common application to macroscopic fungal fruiting bodies than one having precise taxonomic meaning. There are approximately 14,000 described species of mushrooms[2]. # Mushrooms vs. Toadstools The terms "mushrooms" and "toadstools" go back centuries, and were never precisely defined, nor was there consensus on application. The term "toadstool" was often but not exclusively, applied to poisonous mushrooms or to those that have the classic umbrella-like cap-and-stem form. For an example of early usage see Badham (1863[1]). Reference was made to "tadstoles", "frogstooles", "frogge stoles", "tadstooles", "tode stoles", "toodys hatte","paddockstool", "puddockstool", "paddocstol", "toadstoole", and "paddockstooles" from 1398-1597, sometimes synonymous with "mushrom", "mushrum", "muscheron", "mousheroms", "mussheron", or "musserouns" [3]. The term "mushroom" and its variations may have been derived from the French word "Mousseron" in reference to moss (mousse). There may have been a direct connection to toads (in reference to poisonous properties) for toadstools. However, there is no clear-cut delimitation between edible and poisonous fungi, so that mushrooms may be edible, poisonous, or unpalatable, and it makes no sense to not be able to use the term mushroom when stating there are "poisonous mushrooms" which would be an oxymoron if the term mushroom could not be applied to poisonous fungi. The term toadstool is nowadays used in story telling when referring to poisonous or suspect mushrooms, and mycologists avoid the use of the term as it is highly ambiguous. The classic example of a toadstool is Amanita muscaria. # To mushroom - mushrooming - to pop up like mushrooms Many species of mushrooms seemingly appear overnight, growing or expanding rapidly. This phenomenon is the source of several commonly used phrases in the English language. In fact all species of mushrooms take several days to form primordial mushroom fruit bodies. The cultivated mushroom as well as the common field mushroom initially form minute fruiting body initials referred to as the pin stage, because of their small size. Slightly expanded they are called buttons, once again because of the relative size and shape. Once such stages are formed, the mushroom can rapidly pull in water from its mycelium and expand, mainly by inflating preformed cells that took several days to form in the primordia. Similarly, there are even more ephemeral mushrooms, like Parasola plicatilis ([2] formerly Coprinus plicatlis) that literally appear overnight and may be gone by late afternoon on hot summer days after rainfall. The primordia form at ground level in lawns in humid spaces under the thatch of lawns and after heavy rainfall or dewy conditions, balloon to full size in a few hours, release spores, then collapse. They "mushroom" to full size. "To mushroom" means to rapidly grow in size, or to sprout up rapidly, i.e., an organization may "mushroom" from national to international almost overnight. To "pop up like mushrooms" is of similar derivation, but also has a gang slang usage. The slang term "mushrooms" is a gang related term [3]for victims accidentally shot as collateral damage simply because they popped up suddenly, as do fungal mushrooms[4]. The term "mushrooming" differs in that it generally refers to the act of gathering mushrooms, in the wild, as in the statement "I'm going mushrooming today." This is often shortened to "shrooming", which has yet another connotation, which is to "do mushrooms". To "do mushrooms" or "shrooms" often refers to taking hallucinogenic mushrooms (see below). Notably, not all mushrooms expand overnight. Many are very slow growing. Those types of mushrooms generally add tissue to their fruitbodies in different manners, such as growing from the edges, or inserting hyphae. The largest living thing in the world is a mushroom. It is known as the honey fungus (Armillaria Ostoyae), and is not particularly a rare mushroom; you may well have one growing on a dead tree stump in your garden. The largest recorded specimen is in Malheur National Forest Oregon USA. It covers 2,200 acres and is between 2,000 and 8,000 years old. Most of it is underground in the form of white mycelia (the mushroom equivilant of roots). # Human use ## Edible mushrooms Edible mushrooms are used extensively in cooking, in many cuisines (notably Chinese, European and Japanese). Though commonly thought to contain little nutritional value, many species of mushrooms are high in fiber, and provide vitamins such as thiamine (B1), riboflavin (B2), niacin (B3), biotin (B7), cobalamins (B12) and ascorbic acid (C), as well as minerals, including iron, selenium, potassium and phosphorus. Mushrooms have been gaining a higher profile for containing antioxidants Ergothioneine and Selenium. Most mushrooms that are sold in supermarkets have been commercially grown on mushroom farms. The most popular of these, Agaricus bisporus, is safe for most people to eat because it is grown in controlled, sterilized environments, though some individuals do not tolerate it well. Several varieties of A. bisporus are grown commercially, including: whites, crimini and portabello. Other cultivated species now available at many grocers include shiitake, maitake or hen-of-the-woods, oyster and enoki. There are a number of species of mushrooms that are poisonous, and although some resemble certain edible species, eating them could be fatal. Eating mushrooms gathered in the wild can be risky and should not be undertaken by individuals not knowledgeable in mushroom identification, unless the individuals limit themselves to a relatively small number of good edible species that are visually distinctive. More generally, and particularly with gilled mushrooms, separating edible from poisonous species requires meticulous attention to detail: there is no single trait by which all toxic mushrooms could be identified, nor one by which all edible mushrooms could be identified. People who collect mushrooms for consumption are known as mycophagists, and the act of collecting them for such is known as mushroom hunting, or simply "mushrooming". ## Toxic mushrooms Of central interest with respect to chemical properties of mushrooms is the fact that many species produce secondary metabolites that render them toxic, mind-altering, or even bioluminescent. Toxicity likely plays a role in protecting the function of the basidiocarp: the mycelium has expended considerable energy and protoplasmic material to develop a structure to efficiently distribute its spores. One defense against consumption and premature destruction is the evolution of chemicals that render the mushroom inedible, either causing the consumer to vomit (see emetics) the meal or avoid consumption altogether. ## Psychoactive mushrooms Psilocybin mushrooms possess psychedelic properties. They are commonly known as "magic mushrooms" or "shrooms", and are available in smart shops in many parts of the world, though some countries have outlawed their sale. A number of other mushrooms are eaten for their psychoactive effects, such as fly agaric, which is used for shamanic purposes by tribes in northeast Siberia. They have also been used in the West to potentiate, or increase, religious experiences. Because of their psychoactive properties, some mushrooms have played a role in native medicine, where they have been used to affect mental and physical healing, and to facilitate visionary states. One such ritual is the Velada ceremony. A representative figure of traditional mushroom use is the shaman and curandera (priest-healer) María Sabina. ## Medicinal mushrooms Currently, many species of mushrooms and fungi utilized as folk medicines for thousands of years are under intense study by ethnobotanists and medical researchers. Maitake, shiitake, and reishi are prominent among those being researched for their potential anti-cancer, anti-viral, and/or immunity-enhancement properties. Psilocybin, originally an extract of certain psychedelic mushrooms, is being studied for its ability to help people suffering from mental disease, such as obsessive-compulsive disorder. Minute amounts have been reported to stop cluster and migraine headache [4]. ## Other uses Mushrooms can be used for dyeing wool and other natural fibers. The chromophores of mushrooms are organic compounds and produce strong and vivid colors, and all colors of the spectrum can be achieved with mushroom dyes. Before the invention of synthetic dyes the mushrooms were the primary sources on dyeing textiles. This technique has survived in Finland, and many Middle Ages re-enactors have revived the skill again[citation needed]. Some fungi, types of polypores, loosely called mushrooms, have been used as fire starters (known as tinder fungi). Ötzi the Iceman was found carrying such fungi. Mushrooms, and other fungi, will likely play an increasingly important role in the development of effective biological remediation and filtration technologies. The US Patent and Trademark officecan be searched for patents related to the latest developments in mycoremediation and mycofiltration.	https://www.wikidoc.org/index.php/Mushroom
15d078636633d58ee4259d202487c75f7bc2cf25	wikidoc	Mycetoma	Mycetoma Synonyms and keywords: Madura foot. # Overview Mycetoma, or Madura Foot, is an important disease in arid and semi-arid regions around the globe. It is found in Brazil, Mexico, the Sahel, in pan-Arabia, and in semi-arid areas of India. It is found as far north as Romania. There are two known forms of mycetoma. The two forms of mycetoma are bacterial mycetoma and fungal mycetoma: bacterial mycetoma is known as actinomycetoma while the fungal form is called eumycetoma. Even at the level of electron microscopy the two forms of mycetoma are difficult to distinguish from one another. # Pathogenesis The disease is usually acquired while performing agricultural work, and it generally afflicts men between 20 and 40 years old.The disease is acquired by contacting grains of bacterial or fungal spores that have been discharged onto the soil. Infection usually involves an open area or break in the skin. Pseudoallescheria boydii is one of many fungi spp. that causes the fungal form of madura foot (see below). The disease is characterized by a yogurt-like discharge upon maturation of the infection. Hematogenous or lymphatic spread is uncommon. Infections normally start in the foot or hand and travel up the leg or arm. # Diagnosis Diagnosis of mycetoma is usually accomplished by radiology, ultrasound or by fine needle aspiration of the fluid within an afflicted area of the body. # Physical examination ## Gallery - url = > - url = > - url = > - url = > - url = > # Treatment There are several clinical treatments available for this disease. They include surgery, Ketoconazole, Itraconazole and amputation. There is no sure-fire treatment available at this date. Nor is there available at this date a vaccine for mycetoma. Scientists at such institutions as The Mycetoma Research Center at The University of Khartoum in the Sudan are working on a cure. # Causative species Species of bacteria that cause Mycetoma include: - Actinomadura madurae - Actinomadura pelletierii - Streptomyces somaliensis' Species of fungus that cause Mycetoma include: - Madurella myceomatis - Scedosporium apiospermum - Leptosphaeria sengalensis - Madurella grisea	Mycetoma Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]. Synonyms and keywords: Madura foot. # Overview Mycetoma, or Madura Foot, is an important disease in arid and semi-arid regions around the globe. It is found in Brazil, Mexico, the Sahel, in pan-Arabia, and in semi-arid areas of India. It is found as far north as Romania. There are two known forms of mycetoma. The two forms of mycetoma are bacterial mycetoma and fungal mycetoma: bacterial mycetoma is known as actinomycetoma while the fungal form is called eumycetoma. Even at the level of electron microscopy the two forms of mycetoma are difficult to distinguish from one another. # Pathogenesis The disease is usually acquired while performing agricultural work, and it generally afflicts men between 20 and 40 years old.The disease is acquired by contacting grains of bacterial or fungal spores that have been discharged onto the soil. Infection usually involves an open area or break in the skin. Pseudoallescheria boydii is one of many fungi spp. that causes the fungal form of madura foot (see below). The disease is characterized by a yogurt-like discharge upon maturation of the infection. Hematogenous or lymphatic spread is uncommon. Infections normally start in the foot or hand and travel up the leg or arm. # Diagnosis Diagnosis of mycetoma is usually accomplished by radiology, ultrasound or by fine needle aspiration of the fluid within an afflicted area of the body. # Physical examination ## Gallery - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=306> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=306> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=306> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=306> - url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=306> # Treatment There are several clinical treatments available for this disease. They include surgery, Ketoconazole, Itraconazole and amputation. There is no sure-fire treatment available at this date. Nor is there available at this date a vaccine for mycetoma. Scientists at such institutions as The Mycetoma Research Center at The University of Khartoum in the Sudan are working on a cure. # Causative species Species of bacteria that cause Mycetoma include: - Actinomadura madurae - Actinomadura pelletierii - Streptomyces somaliensis' Species of fungus that cause Mycetoma include: - Madurella myceomatis - Scedosporium apiospermum - Leptosphaeria sengalensis - Madurella grisea	https://www.wikidoc.org/index.php/Mycetoma
3e3a904a45e95ff2aba8228b69bf87243d5a4224	wikidoc	Myocilin	Myocilin Myocilin, trabecular meshwork inducible glucocorticoid response, also known as MYOC, is a protein which in humans is encoded by the MYOC gene. Mutations in MYOC are a major cause of glaucoma. # Gene location The cytogenetic location of human MYOC gene is on the long (q) arm of chromosome 1, specifically at position 24.3 (1q24.3). The gene’s molecular location starts at is 171,635,417 bp and ends at 171,652,63 bp on chromosome 1 (Annotation: GRCh38.p12) (assembly). # Protein characteristics Myocilin is a protein with a weight of 55 kDa (504 amino acid) and an overall acidic property is the first gene that has been linked to Primary Open Angle Glaucoma (POAG). ## Protein structure The protein is made up of the two folding domains, the leucine zipper-like domain at the N-terminal and an olfactomedin-like domain at the C-terminal. The domain at the N-terminal is known to have 77.6% homology to the myosin heavy chain of Dictyostelium discoideum and 25% homology with the cardiac β-myosin heavy chain. The gene encodes three different exons, each consisting of different structural and functional domains. The N-terminal is encoded by exon 1 and contains the leucine zipper structural motif, which consists of 50 amino acid residues (117-169 amino acids). The motif is found on an α-helix, which enhances the binding of the protein. The name of the domain arises due to the occurrence of leucine as well as, arginine repeats periodically on the α-helix. The leucine zipper domain also contains the myocilin-myocilin interactions between amino acid residues 117-166. Exon 2 encodes the central region of the protein at amino acid residues 203-245 however, no structural or functional domains are found in this region. Exon 3 encodes the C-terminal of myocilin and has been found to contain the olfactomedin-like domain. The olfactomedin is an extracellular matrix protein with no defined role but is abundantly found in the olfactory neuroepithelium. In the myocilin protein, the domain consists of a single disulfide bond which connects two cysteine residues (245 and 433 amino acids). ## Protein localisation Myocilin is specifically located in the ciliary rootlet and basal body which connects to the cilium of photoreceptor cells in the rough endoplasmic reticulum. The intracellularly distributed protein is processed in the endoplasmic reticulum (ER) and in secreted into the aqueous humour. It is only imported into the trabecular meshwork of the mitochondria. In the extracellular space, it appears in the trabecular meshwork cells through an unconventional mechanism which is associated with exosome-like vesicles. Myocilin localises in the Golgi apparatus of corneal fibroblasts and Schlemm's canal endothelial cells. # Protein processing Several isoforms are produced due to post-translational modifications processes including, glycosylation and palmitoylation. The gene undergoes N-glycosylation at the Asn-Glu-Ser site (57–59 amino acids) and O-glycosylation throughout the protein at the Ser-Pro, Pro-Ser, Thr-Xaa-Xaa-Pro, Ser-Xaa-Xaa-Xaa-Pro sites. Myocilin also undergoes a proteolytic cleavage in the endoplasmic reticulum at residue Arg-226. The cleavage process is calcium dependant and results in two fragments. One fragment contains the C-terminal olfactomedin-like domain (35 kDa), and the other contains the N-terminal leucine zipper-like domain (20 kDa). # Function MYOC encodes the protein myocilin. The precise function of myocilin is unknown, but it is normally secreted into the aqueous humor of the eye. MYOC mutations, which cause myocilin to accumulate in the cells of the trabecular meshwork are a common cause of glaucoma. Most MYOC mutations identified in glaucoma patients are heterozygous and are confined to the olfactomedin domain, which is encoded by exon 3. Myocilin is believed to have a role in cytoskeletal function. MYOC is expressed in many ocular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. Scientific research has found the function of myocilin to be linked with other proteins, making it part of a protein complex. The isoform of the cytochrome P450 protein, 1B1 (CYP1B1) has shown interaction with myocilin. CYP1B1 is also found in several structures so the eye including, trabecular meshwork and the ciliary body. # Mutations and associated diseases Differing mutations in the MYOC gene have been reported to associate with glaucoma 1, open angle (GLC1A) and glaucoma 3, primary congenital (GLC3A). ## Glaucoma 1, open angle (GLC1A) Glaucoma 1 is a form of primary open-angle glaucoma (POAG), which is characterized based on a specific pattern of defects in the optic nerve, thus causing visual defects. The disease causes an angle in the anterior chamber of the eye to be left open, which in turn causes the intraocular pressure to be increased. Although an increase in the intraocular pressure is a major factor for glaucoma, the disease can occur independently of the intraocular pressure. Furthermore, the damage done to the optical nerve has been classified as irreversible because no symptoms of the disease are apparent (asymptomatic) until its last stages. ## Glaucoma 3, primary congenital (GLC3A) Glaucoma 3 arises due to mutations in the distinct genetic loci of MYOC. This mutation contributes to GLC3A through digenic inheritance with the CYP1B1 protein. The mutation gives rise to an autosomal recessive form of primary congenital glaucoma (PCG). The disease initiates at birth or in early childhood due to the increase in intraocular pressure, large ocular globes (buphthalmos) and corneal edema. The progression of the disease causes defects in the trabecular meshwork and anterior chamber angle of the eye preventing the drainage from the aqueous humor. Overall frequency of disease-causing mutations at MYOC in different races: # Clinical significance MYOC contains a signal sequence for secretion and is secreted into the aqueous humor of the eye by the trabecular meshwork. Mutations in MYOC are found in 4% of adult-onset primary open-angle glaucoma and >10% of juvenile-onset primary open-angle glaucoma. Overexpression or underexpression of MYOC does not cause glaucoma. However, the MYOC gene also contains a signal sequence, which is normally not functional, that directs intracellular proteins to peroxisomes. Glaucoma-associated mutations activate that signal sequence and direct myocilin to peroxisomes, where they accumulate in the cell, instead of being secreted. Decreased secretion and increased accumulation appear to be the initial steps in myocilin-associated glaucoma. A study employing iterative pocket & ligand-similarity based approach to virtual ligand screening predicted small molecule binders for the olfactomedin domain of human myocilin. The predictions were subsequently assessed by differential scanning fluorimetry. # Interactions MYOC has been shown to interact with the following proteins: - OLFM3 - FN1 - NRCAM - GLDN - NFASC - MYL2 - SFRP1 - FRZB - FZD7 - FZD10 - FZD1 - WIF1 - SNTA1 - ERBB2 - ERBB3 - SNCG	Myocilin Myocilin, trabecular meshwork inducible glucocorticoid response, also known as MYOC, is a protein which in humans is encoded by the MYOC gene.[1][2] Mutations in MYOC are a major cause of glaucoma. # Gene location The cytogenetic location of human MYOC gene is on the long (q) arm of chromosome 1, specifically at position 24.3 (1q24.3).[3] The gene’s molecular location starts at is 171,635,417 bp and ends at 171,652,63 bp on chromosome 1 (Annotation: GRCh38.p12) (assembly). # Protein characteristics Myocilin is a protein with a weight of 55 kDa (504 amino acid) and an overall acidic property is the first gene that has been linked to Primary Open Angle Glaucoma (POAG).[1] ## Protein structure The protein is made up of the two folding domains, the leucine zipper-like domain at the N-terminal and an olfactomedin-like domain at the C-terminal. The domain at the N-terminal is known to have 77.6% homology to the myosin heavy chain of Dictyostelium discoideum and 25% homology with the cardiac β-myosin heavy chain.[2][4] The gene encodes three different exons, each consisting of different structural and functional domains.[5] The N-terminal is encoded by exon 1 and contains the leucine zipper structural motif, which consists of 50 amino acid residues (117-169 amino acids).[4] The motif is found on an α-helix, which enhances the binding of the protein. The name of the domain arises due to the occurrence of leucine as well as, arginine repeats periodically on the α-helix.[5][4] The leucine zipper domain also contains the myocilin-myocilin interactions between amino acid residues 117-166.[6] Exon 2 encodes the central region of the protein at amino acid residues 203-245 however, no structural or functional domains are found in this region. Exon 3 encodes the C-terminal of myocilin and has been found to contain the olfactomedin-like domain.[7] The olfactomedin is an extracellular matrix protein with no defined role but is abundantly found in the olfactory neuroepithelium.[7] In the myocilin protein, the domain consists of a single disulfide bond which connects two cysteine residues (245 and 433 amino acids).[8] ## Protein localisation Myocilin is specifically located in the ciliary rootlet and basal body which connects to the cilium of photoreceptor cells in the rough endoplasmic reticulum. The intracellularly distributed protein is processed in the endoplasmic reticulum (ER) and in secreted into the aqueous humour.[9] It is only imported into the trabecular meshwork of the mitochondria. In the extracellular space, it appears in the trabecular meshwork cells through an unconventional mechanism which is associated with exosome-like vesicles. Myocilin localises in the Golgi apparatus of corneal fibroblasts and Schlemm's canal endothelial cells.[10][11] # Protein processing Several isoforms are produced due to post-translational modifications processes including, glycosylation and palmitoylation.[12] The gene undergoes N-glycosylation at the Asn-Glu-Ser site (57–59 amino acids) and O-glycosylation throughout the protein at the Ser-Pro, Pro-Ser, Thr-Xaa-Xaa-Pro, Ser-Xaa-Xaa-Xaa-Pro sites.[12][13] Myocilin also undergoes a proteolytic cleavage in the endoplasmic reticulum at residue Arg-226. The cleavage process is calcium dependant and results in two fragments.[14] One fragment contains the C-terminal olfactomedin-like domain (35 kDa), and the other contains the N-terminal leucine zipper-like domain (20 kDa).[5][14] # Function MYOC encodes the protein myocilin. The precise function of myocilin is unknown, but it is normally secreted into the aqueous humor of the eye. MYOC mutations, which cause myocilin to accumulate in the cells of the trabecular meshwork are a common cause of glaucoma. Most MYOC mutations identified in glaucoma patients are heterozygous and are confined to the olfactomedin domain, which is encoded by exon 3.[4] Myocilin is believed to have a role in cytoskeletal function. MYOC is expressed in many ocular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma.[15] Scientific research has found the function of myocilin to be linked with other proteins, making it part of a protein complex. The isoform of the cytochrome P450 protein, 1B1 (CYP1B1) has shown interaction with myocilin. CYP1B1 is also found in several structures so the eye including, trabecular meshwork and the ciliary body.[16] # Mutations and associated diseases Differing mutations in the MYOC gene have been reported to associate with glaucoma 1, open angle (GLC1A) and glaucoma 3, primary congenital (GLC3A). ## Glaucoma 1, open angle (GLC1A) Glaucoma 1 is a form of primary open-angle glaucoma (POAG), which is characterized based on a specific pattern of defects in the optic nerve, thus causing visual defects.[1][17] The disease causes an angle in the anterior chamber of the eye to be left open, which in turn causes the intraocular pressure to be increased. Although an increase in the intraocular pressure is a major factor for glaucoma, the disease can occur independently of the intraocular pressure.[17] Furthermore, the damage done to the optical nerve has been classified as irreversible because no symptoms of the disease are apparent (asymptomatic) until its last stages.[17] ## Glaucoma 3, primary congenital (GLC3A) Glaucoma 3 arises due to mutations in the distinct genetic loci of MYOC. This mutation contributes to GLC3A through digenic inheritance with the CYP1B1 protein.[16] The mutation gives rise to an autosomal recessive form of primary congenital glaucoma (PCG). The disease initiates at birth or in early childhood due to the increase in intraocular pressure, large ocular globes (buphthalmos) and corneal edema. The progression of the disease causes defects in the trabecular meshwork and anterior chamber angle of the eye preventing the drainage from the aqueous humor.[16] Overall frequency of disease-causing mutations at MYOC in different races[18]: # Clinical significance MYOC contains a signal sequence for secretion and is secreted into the aqueous humor of the eye by the trabecular meshwork. Mutations in MYOC are found in 4% of adult-onset primary open-angle glaucoma and >10% of juvenile-onset primary open-angle glaucoma. Overexpression or underexpression of MYOC does not cause glaucoma. However, the MYOC gene also contains a signal sequence, which is normally not functional, that directs intracellular proteins to peroxisomes. Glaucoma-associated mutations activate that signal sequence and direct myocilin to peroxisomes, where they accumulate in the cell, instead of being secreted. Decreased secretion and increased accumulation appear to be the initial steps in myocilin-associated glaucoma.[19] A study employing iterative pocket & ligand-similarity based approach to virtual ligand screening predicted small molecule binders for the olfactomedin domain of human myocilin. The predictions were subsequently assessed by differential scanning fluorimetry.[20] # Interactions MYOC has been shown to interact with the following proteins:[12][21][22][23] - OLFM3 - FN1 - NRCAM - GLDN - NFASC - MYL2 - SFRP1 - FRZB - FZD7 - FZD10 - FZD1 - WIF1 - SNTA1 - ERBB2 - ERBB3 - SNCG	https://www.wikidoc.org/index.php/Myocilin
13ccef8c0abcb50cd03e6327ea46d1daf8b7b181	wikidoc	Myogenin	Myogenin Myogenin (myogenic factor 4), also known as MYOG, is a gene. Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and Mrf4. In mice, myogenin is essential for the development of functional skeletal muscle. Myogenin is required for the proper differentiation of most myogenic precursor cells during the process of myogenesis. When the DNA coding for myogenin was knocked out of the mouse genome, severe skeletal muscle defects were observed. Mice lacking both copies of myogenin (homozygous-null) suffer from perinatal lethality due to the lack of mature secondary skeletal muscle fibers throughout the body. In cell culture, myogenin can induce myogenesis in a variety of non-muscle cell types. # Interactions Myogenin has been shown to interact with: - MDFI, - POLR2C, - Serum response factor - Sp1 transcription factor, and - TCF3.	Myogenin Myogenin (myogenic factor 4), also known as MYOG, is a gene.[1] Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and Mrf4. In mice, myogenin is essential for the development of functional skeletal muscle. Myogenin is required for the proper differentiation of most myogenic precursor cells during the process of myogenesis. When the DNA coding for myogenin was knocked out of the mouse genome, severe skeletal muscle defects were observed. Mice lacking both copies of myogenin (homozygous-null) suffer from perinatal lethality due to the lack of mature secondary skeletal muscle fibers throughout the body.[2][3] In cell culture, myogenin can induce myogenesis in a variety of non-muscle cell types. # Interactions Myogenin has been shown to interact with: - MDFI,[4] - POLR2C,[5] - Serum response factor[6][7] - Sp1 transcription factor,[6] and - TCF3.[8][9]	https://www.wikidoc.org/index.php/Myogenin
9ec60e55f0035bb7938e1fbaee532002e4e5c6ed	wikidoc	Myositis	Myositis Synonyms and keywords: # Overview Myositis is a general term for inflammation of the muscles. Many such conditions are considered likely to be caused by autoimmune conditions, rather than directly due to infection (although autoimmune conditions can be activated or exacerbated by infections.) Elevation of creatine kinase (CK) in blood is indicative of myositis. The MM and not the MB or BB fraction of the CK will be elevated. # Differential diagnosis of myositis Myositis must be differentiated from the following conditions causing muscle weakness, hypotonia, or flaccid paralysis: The following drugs or conditions may additionally need to be differentiated from myositis: Atorvastatin Cellulitis Deep vein thrombosis Dermatomyositis Dolutegravir Hematoma Idiopathic inflammatory myopathies Inclusion body myositis Influenza myositis Juvenile dermatomyositis Lovastatin Lyme myositis Myositis ossificans Neuromuscular complications accompanying AIDS Osteoarthritis Osteomyelitis Paraneoplastic neuropathy Peripheral vascular disease Polymyositis Pravastatin (less likely than other statins) Pyomyositis Rheumatoid arthritis Simvastatin Statin therapy Systemic lupus erythematosus Toxoplasma myositis Trichinosis Trypanosomiasis Tuberculous pyomyositis Viral myositis (including following an episode of influenza) Wasting syndrome ## Causes ## Drug Side Effect - Pembrolizumab - Pergolide - Zidovudine # Diagnostic Findings ## MRI (Images courtesy of RadsWiki) - Myositis Myositis - Myositis Myositis - Myositis Myositis - Myositis Myositis - Myositis Myositis	Myositis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2] Synonyms and keywords: # Overview Myositis is a general term for inflammation of the muscles. Many such conditions are considered likely to be caused by autoimmune conditions, rather than directly due to infection (although autoimmune conditions can be activated or exacerbated by infections.) Elevation of creatine kinase (CK) in blood is indicative of myositis. The MM and not the MB or BB fraction of the CK will be elevated. # Differential diagnosis of myositis Myositis must be differentiated from the following conditions causing muscle weakness, hypotonia, or flaccid paralysis:[1][1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The following drugs or conditions may additionally need to be differentiated from myositis: Atorvastatin Cellulitis Deep vein thrombosis Dermatomyositis Dolutegravir Hematoma Idiopathic inflammatory myopathies Inclusion body myositis Influenza myositis Juvenile dermatomyositis Lovastatin Lyme myositis Myositis ossificans Neuromuscular complications accompanying AIDS Osteoarthritis Osteomyelitis Paraneoplastic neuropathy Peripheral vascular disease Polymyositis Pravastatin (less likely than other statins) Pyomyositis Rheumatoid arthritis Simvastatin Statin therapy Systemic lupus erythematosus Toxoplasma myositis Trichinosis Trypanosomiasis Tuberculous pyomyositis Viral myositis (including following an episode of influenza) Wasting syndrome ## Causes ## Drug Side Effect - Pembrolizumab - Pergolide - Zidovudine # Diagnostic Findings ## MRI (Images courtesy of RadsWiki) - Myositis Myositis - Myositis Myositis - Myositis Myositis - Myositis Myositis - Myositis Myositis	https://www.wikidoc.org/index.php/Myositis
9dd7bb6ff0862a8ed1ccef29c5c780a2cb514033	wikidoc	Myotilin	Myotilin 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 Myotilin, also known as MYOT, is a human gene. Striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin (TTN; MIM 188840), a giant molecule that contains several immunoglobulin (Ig)-like domains and associates with thin and thick filaments, and alpha-actinin (ACTN1; MIM 102575), an actin cross-linking protein. Mutations in several sarcomeric and sarcolemmal proteins have been shown to result in muscular dystrophy and cardiomyopathy.	Myotilin Template:PBB 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 Myotilin, also known as MYOT, is a human gene.[1] Striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin (TTN; MIM 188840), a giant molecule that contains several immunoglobulin (Ig)-like domains and associates with thin and thick filaments, and alpha-actinin (ACTN1; MIM 102575), an actin cross-linking protein. Mutations in several sarcomeric and sarcolemmal proteins have been shown to result in muscular dystrophy and cardiomyopathy.[supplied by OMIM][1]	https://www.wikidoc.org/index.php/Myotilin
a8cbc079009f192bbe95000d3745193967e4b4ac	wikidoc	Myotonia	Myotonia 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 Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation. Generally, repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed-up. However, prolonged, rigorous exercise may also trigger the condition. Individuals with the disorder may have trouble releasing their grip on objects or may have difficulty rising from a sitting position and a stiff, awkward gait. Symptoms of myotonia are more frequently experienced in women during pregnancy. Myotonia can affect all muscle groups, however the pattern of affected muscles can vary depending on the specific disorder involved. It may be acquired or inherited, and is caused by an abnormality in the muscle membrane. Specifically, the ion channels. Myotonia is a symptom commonly seen in patients with myotonic muscular dystrophy, of which two documented types and one speculated type exist, and in a group of disorders called channelopathies (hereditary diseases that are caused by mutations in the chloride, sodium or potassium ion transport channels in the muscle membrane), such as Myotonia Congenita (Congenital Myotonia) of which two types called Becker's Disease and Thomsen's Disease exist. There is also a disorder called Paramyotonia Congenita. Myotonia arising from channelopathies, and myotonic muscular dystrophy can be exacerbated by exposure to cold (and occasionally heat), by eating foods that are potassium-rich (such as bananas), with exertion, especially after long periods of inactivity, sudden surprises, and stressful situations. Myotonia is not always a disease-related or abnormal phenomenon. Humans and other animals often display myotonia when placed in situations of extreme stress or fear; a resultant increase in 'fight-or-flight' hormones such as epinephrine and cortisol may cause increased muscle tension throughout the body. People suffering from disorders involving myotonia can have a life threatening reaction to certain anaesthetics, one of these conditions occurs when the patient is under anaesthetic and is termed " Malignant Hyperthermia ". Anaesthetics cannot diagnose this condition until the patient is under anaesthetic so this condition is very life threatening.	Myotonia Template:DiseaseDisorder infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. # Overview Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation. Generally, repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed-up. However, prolonged, rigorous exercise may also trigger the condition. Individuals with the disorder may have trouble releasing their grip on objects or may have difficulty rising from a sitting position and a stiff, awkward gait. Symptoms of myotonia are more frequently experienced in women during pregnancy. Myotonia can affect all muscle groups, however the pattern of affected muscles can vary depending on the specific disorder involved. It may be acquired or inherited, and is caused by an abnormality in the muscle membrane. Specifically, the ion channels. Myotonia is a symptom commonly seen in patients with myotonic muscular dystrophy, of which two documented types and one speculated type exist, and in a group of disorders called channelopathies (hereditary diseases that are caused by mutations in the chloride, sodium or potassium ion transport channels in the muscle membrane), such as Myotonia Congenita (Congenital Myotonia) of which two types called Becker's Disease and Thomsen's Disease exist. There is also a disorder called Paramyotonia Congenita. Myotonia arising from channelopathies, and myotonic muscular dystrophy can be exacerbated by exposure to cold (and occasionally heat), by eating foods that are potassium-rich (such as bananas), with exertion, especially after long periods of inactivity, sudden surprises, and stressful situations. Myotonia is not always a disease-related or abnormal phenomenon. Humans and other animals often display myotonia when placed in situations of extreme stress or fear; a resultant increase in 'fight-or-flight' hormones such as epinephrine and cortisol may cause increased muscle tension throughout the body. People suffering from disorders involving myotonia can have a life threatening reaction to certain anaesthetics, one of these conditions occurs when the patient is under anaesthetic and is termed " Malignant Hyperthermia ". Anaesthetics cannot diagnose this condition until the patient is under anaesthetic so this condition is very life threatening.	https://www.wikidoc.org/index.php/Myotonia
a01b6dd39c2bcc4d061a5af775896e67ffe49eb0	wikidoc	Myxedema	Myxedema Please help WikiDoc by adding more content here. It's easy! Click here to learn about editing. Synonyms and keywords: Myxoedema; # Overview Myxedema is a skin and tissue disorder usually due to severe prolonged hypothyroidism. Hypothyroidism can be caused by Hashimoto's thyroiditis, surgical removal of the thyroid, and rarer conditions. Partial forms of myxedema, especially of the lower legs (called pretibial myxedema), occasionally occur in adults with Graves' disease, a cause of hyperthyroidism; or also Hashimoto's thyroiditis without severe hypothyroidism. # Pathophysiology Myxedema stemming from both the hyperthyroid and hypothyroid conditions, results from the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesional and normal skin. The mechanism that causes myxedema is still not yet understood, although animal model studies suggest that thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts. The fibroblasts in the orbital and pretibial dermis share antigenic sites that underlie the autoimmune process that causes Grave's disease. This cross-reaction may contribute to the development of myxedema long after normal levels of thyroid hormones have been restored by treatment. # Causes - Hashimoto's thyroiditis - Drug side effects: - Potassium iodide # Differentiating myxedema from other diseases Myxedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lipedema, lymphatic filariasis, cellulitis and causes of generalized edema. # Diagnosis ## Symptoms Myxedema usually presents itself with some of the following symptoms: - Skin thickening - Coarse skin - Change in facial appearance - Thickening nose - Swollen lips - Puffiness around the eyes - Jelly-like infiltrations in subcutaneous tissues - Slow speech - Mental dullness - Lethargy - Mental problems - Dry skin - Yellow skin - Swollen subcutaneous tissue - Weight gain - Constipation - Thinning hair - Brittle hair - Bald patches - Muscle pains - Deafness - Hearing impairment - Carpal tunnel syndrome # Treatment Treatment for myxedema is difficult. Systemic or intralesional glucocorticoids, topical glucocorticoids under occlusion or high-dose intravenous immunoglobulin have been reported to offer some relief to patients. Treatment should follow correction of the original hyperthyroidism/hypothyroidism. # Related Chapters - Cretinism - congenital hypothyroidism	Myxedema Please help WikiDoc by adding more content here. It's easy! Click here to learn about editing. Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: Myxoedema; # Overview Myxedema is a skin and tissue disorder usually due to severe prolonged hypothyroidism. Hypothyroidism can be caused by Hashimoto's thyroiditis, surgical removal of the thyroid, and rarer conditions. Partial forms of myxedema, especially of the lower legs (called pretibial myxedema), occasionally occur in adults with Graves' disease, a cause of hyperthyroidism; or also Hashimoto's thyroiditis without severe hypothyroidism. # Pathophysiology Myxedema stemming from both the hyperthyroid and hypothyroid conditions, results from the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesional and normal skin. The mechanism that causes myxedema is still not yet understood, although animal model studies suggest that thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts. The fibroblasts in the orbital and pretibial dermis share antigenic sites that underlie the autoimmune process that causes Grave's disease. This cross-reaction may contribute to the development of myxedema long after normal levels of thyroid hormones have been restored by treatment. # Causes - Hashimoto's thyroiditis - Drug side effects: - Potassium iodide # Differentiating myxedema from other diseases Myxedema must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lipedema, lymphatic filariasis, cellulitis and causes of generalized edema. # Diagnosis ## Symptoms Myxedema usually presents itself with some of the following symptoms: - Skin thickening - Coarse skin - Change in facial appearance - Thickening nose - Swollen lips - Puffiness around the eyes - Jelly-like infiltrations in subcutaneous tissues - Slow speech - Mental dullness - Lethargy - Mental problems - Dry skin - Yellow skin - Swollen subcutaneous tissue - Weight gain - Constipation - Thinning hair - Brittle hair - Bald patches - Muscle pains - Deafness - Hearing impairment - Carpal tunnel syndrome # Treatment Treatment for myxedema is difficult. Systemic or intralesional glucocorticoids, topical glucocorticoids under occlusion or high-dose intravenous immunoglobulin have been reported to offer some relief to patients. Treatment should follow correction of the original hyperthyroidism/hypothyroidism. # Related Chapters - Cretinism - congenital hypothyroidism	https://www.wikidoc.org/index.php/Myxedema
f1f8067f4a6310ecdba85080b89d6bdef45010fe	wikidoc	NCLEX-PN	NCLEX-PN Assistant Editor-In-Chief: Michelle Lew # Overview The NCLEX-PN (National Council Licensure EXamination-Practical Nurse) is a computer-adaptive test of entry-level nursing competence. Passing the exam is required of candidates for licensure as a Licensed Practical Nurse (LPN) or Licensed Vocational Nurse (LVN) by all US state and territorial Boards of Nursing. The NCLEX-RN® and NCLEX-PN® examinations are developed and owned by the National Council of State Boards of Nursing, Inc. (NCSBN®). NCSBN administers these examinations on behalf of its member boards which consist of the boards of nursing in the 50 states, the District of Columbia, and four U.S. territories American Samoa, Guam, Northern Mariana Islands and the Virgin Islands. To ensure public protection, each board of nursing requires a candidate for licensure to pass the appropriate NCLEX® examination, NCLEX-RN for registered nurses and the NCLEX-PN for practical/vocational nurses. NCLEX examinations are designed to test the knowledge, skills and abilities essential to the safe and effective practice of nursing at the entry-level. NCLEX examinations are provided in a computerized adaptive testing (CAT) format and are presently administered by Pearson VUE in their network of Pearson Professional Centers (PPC). CAT is a method for administering tests that merges existing computer technology with modern measurement theory to increase the efficiency of the testing process. The NCLEX examination uses items with a variety of response formats, such as, single response multiple-choice, multiple response, fill-in-the-blank, drag and drop and a variety of display formats, such as, chart/exhibit displays, tables, and graphic images. All items are developed and validated using the expertise of practicing nurses, educators and regulators from throughout the country. The content of the items of the NCLEX examinations is based on a practice analysis conducted every three years. # Exam content The majority of test items are written at the application or higher levels of cognition but the exam may include items at all of the cognitive levels. The exam's content is based on client needs: - Safe Effective Care Environment Coordinated Care Safety and Infection Control - Coordinated Care - Safety and Infection Control - Health Promotion and Maintenance - Psychosocial Integrity - Physiological Integrity Basic Care and Comfort Pharmacological Therapies Reduction of Risk Potential Physiological Adaptation - Basic Care and Comfort - Pharmacological Therapies - Reduction of Risk Potential - Physiological Adaptation	NCLEX-PN Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assistant Editor-In-Chief: Michelle Lew # Overview Template:Expand The NCLEX-PN (National Council Licensure EXamination-Practical Nurse) is a computer-adaptive test of entry-level nursing competence. Passing the exam is required of candidates for licensure as a Licensed Practical Nurse (LPN) or Licensed Vocational Nurse (LVN) by all US state and territorial Boards of Nursing. The NCLEX-RN® and NCLEX-PN® examinations are developed and owned by the National Council of State Boards of Nursing, Inc. (NCSBN®). NCSBN administers these examinations on behalf of its member boards which consist of the boards of nursing in the 50 states, the District of Columbia, and four U.S. territories American Samoa, Guam, Northern Mariana Islands and the Virgin Islands. To ensure public protection, each board of nursing requires a candidate for licensure to pass the appropriate NCLEX® examination, NCLEX-RN for registered nurses and the NCLEX-PN for practical/vocational nurses. NCLEX examinations are designed to test the knowledge, skills and abilities essential to the safe and effective practice of nursing at the entry-level. NCLEX examinations are provided in a computerized adaptive testing (CAT) format and are presently administered by Pearson VUE in their network of Pearson Professional Centers (PPC). CAT is a method for administering tests that merges existing computer technology with modern measurement theory to increase the efficiency of the testing process. The NCLEX examination uses items with a variety of response formats, such as, single response multiple-choice, multiple response, fill-in-the-blank, drag and drop and a variety of display formats, such as, chart/exhibit displays, tables, and graphic images. All items are developed and validated using the expertise of practicing nurses, educators and regulators from throughout the country. The content of the items of the NCLEX examinations is based on a practice analysis conducted every three years. . # Exam content The majority of test items are written at the application or higher levels of cognition but the exam may include items at all of the cognitive levels. The exam's content is based on client needs: - Safe Effective Care Environment Coordinated Care Safety and Infection Control - Coordinated Care - Safety and Infection Control - Health Promotion and Maintenance - Psychosocial Integrity - Physiological Integrity Basic Care and Comfort Pharmacological Therapies Reduction of Risk Potential Physiological Adaptation - Basic Care and Comfort - Pharmacological Therapies - Reduction of Risk Potential - Physiological Adaptation	https://www.wikidoc.org/index.php/NCLEX-PN
a23e10751c80f95c7bdfdfb4e6ef087286ed6995	wikidoc	NDUFA4L2	NDUFA4L2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 is a protein that in humans is encoded by the NDUFA4L2 gene. The NDUFA4L2 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. # Structure The NDUFA4L2 gene is located on the long q arm of chromosome 12 at position 13.3 and it spans 5,860 base pairs. NDUFA4L2 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. # Function The human NDUFA4L2 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.	NDUFA4L2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 is a protein that in humans is encoded by the NDUFA4L2 gene.[1] The NDUFA4L2 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2] # Structure The NDUFA4L2 gene is located on the long q arm of chromosome 12 at position 13.3 and it spans 5,860 base pairs.[1] NDUFA4L2 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[2] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[1] # Function The human NDUFA4L2 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[1] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2]	https://www.wikidoc.org/index.php/NDUFA4L2
eed07d1caafd1417242096e7b6e4dc85a588d2df	wikidoc	Nadorite	Nadorite Nadorite is a mineral with the chemical formula PbSb. In the orthorhombic crystal system, Nadorite is brown, brownish-yellow or yellow in colour, with a white or yellowish-white streak. With a Mohs hardness of 3½ to 4, it has one perfect cleavage. Nadorite is named after Djebel Nador in Algeria, where it was first identified in 1870. Djebel Nador and Djebel Debbar (both in the Constantine Province of Algeria) are its co-type localities.	Nadorite Template:Infobox mineral Nadorite is a mineral with the chemical formula PbSb[O2\|Cl].[1] In the orthorhombic crystal system, Nadorite is brown, brownish-yellow or yellow in colour, with a white or yellowish-white streak.[1] With a Mohs hardness of 3½ to 4, it has one perfect cleavage.[1] Nadorite is named after Djebel Nador in Algeria, where it was first identified in 1870.[1] Djebel Nador and Djebel Debbar (both in the Constantine Province of Algeria) are its co-type localities.[1]	https://www.wikidoc.org/index.php/Nadorite
7c1eebdd48f35b8b71198341cded21007024cb28	wikidoc	Naloxone	Naloxone # 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 Naloxone is an opioid antagonist that is FDA approved for the treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Common adverse reactions include hypotension, hypertension, ventricular tachycardia, ventricular fibrillation, dyspnea, pulmonary edema, cardiac arrest, death, coma, and encephalopathy. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. - Naloxone is intended for immediate administration as emergency therapy in settings where opioids may be present. - Naloxone is not a substitute for emergency medical care. - Administer the initial dose of Naloxone to adult intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary, and seek emergency medical assistance. Administer Naloxone as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. The requirement for repeat doses of Naloxone depends upon the amount, type, and route of administration of the opioid being antagonized. - If the desired response is not obtained after 2 or 3 minutes, another Naloxone dose may be administered. If there is still no response and additional doses are available, additional Naloxone doses may be administered every 2 to 3 minutes until emergency medical assistance arrives. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. - Injection: 0.4 mg/0.4 mL naloxone hydrochloride solution in a pre-filled auto-injector. Each Naloxone delivers 0.4 mg naloxone hydrochloride injection (0.4 mL). ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Naloxone in adult patients. ### Non–Guideline-Supported Use - Naloxone 20 mg or 40 mg. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. - Naloxone is intended for immediate administration as emergency therapy in settings where opioids may be present. - Naloxone is not a substitute for emergency medical care. - Administer the initial dose of Naloxone to pediatric patients intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary, and seek emergency medical assistance. Administer Naloxone as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. The requirement for repeat doses of Naloxone depends upon the amount, type, and route of administration of the opioid being antagonized. - If the desired response is not obtained after 2 or 3 minutes, another Naloxone dose may be administered. If there is still no response and additional doses are available, additional Naloxone doses may be administered every 2 to 3 minutes until emergency medical assistance arrives. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. - In pediatric patients under the age of one, the caregiver should pinch the thigh muscle while administering Naloxone. - Injection: 0.4 mg/0.4 mL naloxone hydrochloride solution in a pre-filled auto-injector. Each Naloxone delivers 0.4 mg naloxone hydrochloride injection (0.4 mL). ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Naloxone in pediatric patients. ### Non–Guideline-Supported Use - Naloxone 0.05 mg IM. # Contraindications - Naloxone is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients. # Warnings ### Precautions - Duration of Effect - The duration of action of most opioids is likely to exceed that of Naloxone resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek immediate emergency medical assistance after delivering the first dose of Naloxone, keep the patient under continued surveillance, and repeat doses of Naloxone as necessary. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. Large doses of naloxone hydrochloride are required to antagonize buprenorphine because the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression. - Precipitation of Severe Opioid Withdrawal - The use of Naloxone in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. - Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. These events have occurred in patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, after use of naloxone hydrochloride, patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects should be monitored for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting. It has been suggested that the pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures. # Adverse Reactions ## Clinical Trials Experience - The following adverse reactions have been identified during post-approval use of naloxone hydrochloride in the post-operative setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia and have caused agitation. - Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, hyperactive reflexes. ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Naloxone in the drug label. # Drug Interactions There is limited information regarding Naloxone Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category B - Risk Summary - There are no adequate and well-controlled studies with Naloxone in pregnant women. Animal studies were conducted with naloxone hydrochloride given during organogenesis in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day. These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Because animal reproduction studies are not always predictive of human response, Naloxone should be used during pregnancy only if clearly needed. - Clinical Considerations - Naloxone hydrochloride crosses the placenta, and may precipitate withdrawal in the fetus as well as in the opioid-dependent mother. The fetus should be evaluated for signs of distress after Naloxone is used. Careful monitoring is needed until the fetus and mother are stabilized. - Data - Animal Data - Naloxone hydrochloride was administered during organogenesis to mice and rats at doses 4-times and 8-times, respectively, the dose of 10 mg/day given to a 50 kg human (when based on body surface area or mg/m2). These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Naloxone in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Naloxone during labor and delivery. ### Nursing Mothers - It is not known whether naloxone hydrochloride is present in human milk. Because many drugs are present in human milk, exercise caution when Naloxone is administered to a nursing woman. ### Pediatric Use - The safety and effectiveness of Naloxone (for intramuscular and subcutaneous use) have been established in pediatric patients for known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Use of naloxone hydrochloride in pediatric patients is supported by evidence from adequate and well-controlled studies of naloxone hydrochloride in adults with additional data from 15 clinical studies (controlled and uncontrolled) in which neonates and pediatric patients received parenteral naloxone in doses ranging from 0.005 mg/kg to 0.01 mg/kg. Safety and effectiveness are also supported by use of other naloxone hydrochloride products in the post-marketing setting as well as data available in the medical literature and clinical practice guidelines. - Absorption of naloxone hydrochloride following subcutaneous or intramuscular administration in pediatric patients may be erratic or delayed. Even when the opiate-intoxicated pediatric patient responds dramatically to naloxone hydrochloride injection, he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized. In opioid-dependent pediatric patients, (including neonates), administration of naloxone may result in an abrupt and complete reversal of opioid effects, precipitating an acute opioid withdrawal syndrome. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts. - In neonates and pediatric patients less than 1 year of age, careful observation of the administration site for evidence of residual needle parts and/or signs of infection is warranted. ### Geriatic Use - Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Therefore, the systemic exposure of naloxone can be higher in these patients. - Clinical studies of naloxone hydrochloride did not include sufficient numbers 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. ### Gender There is no FDA guidance on the use of Naloxone with respect to specific gender populations. ### Race There is no FDA guidance on the use of Naloxone with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Naloxone in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Naloxone in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Naloxone in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Naloxone in patients who are immunocompromised. # Administration and Monitoring ### Administration - Intramuscular - Subcutaneous ### Monitoring There is limited information regarding Monitoring of Naloxone in the drug label. # IV Compatibility There is limited information regarding IV Compatibility of Naloxone in the drug label. # Overdosage ## Chronic Overdose There is limited information regarding Chronic Overdose of Naloxone in the drug label. # Pharmacology ## Mechanism of Action - Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. - Naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine. ## Structure - Naloxone (naloxone hydrochloride injection, USP) is a pre-filled, single-use auto-injector. Naloxone is not made with natural rubber latex. Chemically, naloxone hydrochloride is the hydrochloride salt of 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride with the following structure: - Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. - Each 0.4 mL in Naloxone contains inactive ingredients of 3.34 mg of sodium chloride, hydrochloric acid to adjust pH, and water for injection. The pH range is 3.0 to 4.5. ## Pharmacodynamics - When naloxone hydrochloride is administered intravenously, the onset of action is generally apparent within two minutes. The time to onset of action is shorter for intravenous compared to subcutaneous or intramuscular routes of administration. - The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. ## Pharmacokinetics - In one pharmacokinetic study in 30 healthy subjects, a single 0.4 mg subcutaneous or intramuscular naloxone injection administered using Naloxone provides equivalent naloxone AUC and 15% greater naloxone Cmax in comparison to a single 0.4 mg subcutaneous or intramuscular naloxone injection administered using a standard syringe. - Following a single Naloxone injection, the median Tmax of naloxone was reached at 15 minutes (range 5 minutes to 1.2 hours), with a mean (± SD) Cmax value of 1.24 (± 0.64) ng/mL. The mean (± SD) plasma half-life of naloxone in healthy adults was 1.28 (± 0.48) hours. In the same study, following administration of a single dose of 0.4 mg naloxone injection using a standard syringe, the median Tmax was 20 minutes (range 5 minutes to 2.03 hours) and the mean (± SD) Cmax value was 1.07 (± 0.48) ng/mL. The mean (± SD) plasma half-life was 1.36 (± 0.32) hours. - Distribution - Following parenteral administration, naloxone is distributed in the body and readily crosses the placenta. Plasma protein binding occurs but is relatively weak. Plasma albumin is the major binding constituent but significant binding of naloxone also occurs to plasma constituents other than albumin. It is not known whether naloxone is excreted into human milk. - Metabolism - Naloxone hydrochloride is metabolized in the liver, primarily by glucuronide conjugation with naloxone-3-glucoronide as the major metabolite. - Elimination - After an oral or intravenous dose, about 25-40% of naloxone is excreted as metabolites in urine within 6 hours, about 50% in 24 hours, and 60-70% in 72 hours. Following a single Naloxone injection, the mean (± SD) plasma half-life of naloxone in healthy adults was 1.28 (± 0.48) hours. In a neonatal study of naloxone injection, the mean (± SD) plasma half-life was observed to be 3.1 (± 0.5) hours. ## Nonclinical Toxicology - Carcinogenesis - Long-term animal studies to evaluate the carcinogenic potential of naloxone have not been completed. - Mutagenesis - Naloxone was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. - Impairment of Fertility - Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no adverse effect of naloxone hydrochloride on fertility. # Clinical Studies There is limited information regarding Clinical Studies of Naloxone in the drug label. # How Supplied - Carton containing two Naloxone (naloxone hydrochloride injection, USP) 0.4 mg auto-injectors and a single Trainer for Naloxone - NDC 60842-030-01 - Storage and Handling - Store Naloxone in the outer case provided. - Store at controlled room temperature 15°C to 25°C (59°F to 77°F) excursions permitted between 4°C and 40°C (between 39°F and 104°F). - Before using, check to make sure the solution in the auto-injector is not discolored. Replace Naloxone if the solution is discolored or contains a precipitate. ## Storage There is limited information regarding Naloxone Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information - Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Instructions for Use). - Instruct patients and their family members or caregivers to: - Become familiar with the following information contained in the carton as soon as they receive EVZIO: EVZIO Instructions for Use Trainer for EVZIO Instructions for Use Trainer for EVZIO - EVZIO Instructions for Use - Trainer for EVZIO Instructions for Use - Trainer for EVZIO - Practice using the Trainer before EVZIO is needed. Each EVZIO (which is purple and yellow) can only be used one time; however, the Trainer (which is black and white) can be re-used for training purposes and its red safety guard can be removed and replaced. Both EVZIO and the Trainer for EVZIO incorporate the electronic voice instruction system. - Each EVZIO (which is purple and yellow) can only be used one time; however, the Trainer (which is black and white) can be re-used for training purposes and its red safety guard can be removed and replaced. - Both EVZIO and the Trainer for EVZIO incorporate the electronic voice instruction system. - Make sure EVZIO is present whenever persons may be intentionally or accidentally exposed to an opioid to treat serious opioid overdose (i.e., opioid emergencies). - Instruct the patients and their family members or caregivers how to recognize the signs and symptoms of an opioid overdose requiring the use of EVZIO such as the following: - Extreme sleepiness - inability to awaken a patient verbally or upon a firm sternal rub. - Breathing problems - this can range from slow or shallow breathing to no breathing in a patient who cannot be awakened. - Other signs and symptoms that may accompany sleepiness and breathing problems include the following: - Extremely small pupils (the black circle in the center of the colored part of the eye) sometimes called “pinpoint pupils.” - Slow heartbeat and/or low blood pressure. - Instruct them that when in doubt, if a patient is unresponsive, and an opioid overdose is suspected, administer EVZIO as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. Instruct them to seek emergency medical assistance after administering the first dose of EVZIO. - Duration of Effect - Instruct patients and their family members or caregivers that since the duration of action of most opioids may exceed that of naloxone, seek immediate emergency medical assistance, keep the patient under continued surveillance, and administer repeated doses of EVZIO as necessary. - Limited Efficacy for/with Partial Agonists or Mixed Agonist/Antagonists - Instruct patients and their family members or caregivers that the reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. - Precipitation of Severe Opioid Withdrawal - Instruct patients and their family members or caregivers that the use of EVZIO in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life threatening if not recognized and properly treated, and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. - Administration Instructions - Instruct patients and their family members or caregivers about the following important information: EVZIO is user actuated and may be administered through clothing if necessary. Inject EVZIO while pressing into the anterolateral aspect of the thigh. In pediatric patients less than 1 year of age, pinch the thigh muscle while administering EVZIO. Upon actuation, EVZIO automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone, and retracts the needle fully into its housing. The needle is not visible before, during, or after injection. Each EVZIO can only be used one time. If the electronic voice instruction system on EVZIO does not work properly, EVZIO will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on its label. The electronic voice instructions are independent of activating EVZIO and are not required to wait for the voice instructions to be completed prior to moving to the next step in the injection process. Post-injection, the black base locks in place, a red indicator appears in the viewing window and electronic visual and audible instructions signal that EVZIO has delivered the intended dose of naloxone hydrochloride. EVZIO’s red safety guard should not be replaced under any circumstances. However, the Trainer is designed for re-use and its red safety guard can be removed and replaced. It is recommended that patients and caregivers become familiar with the training device provided and read the Instructions for Use; however, untrained caregivers or family members should still attempt to use EVZIO during a suspected opioid overdose while awaiting definitive emergency medical care. Periodically visually inspect the naloxone solution through the viewing window. If the solution is discolored, cloudy, or contains solid particles, replace it with a new EVZIO. Replace EVZIO before its expiration date. - EVZIO is user actuated and may be administered through clothing if necessary. - Inject EVZIO while pressing into the anterolateral aspect of the thigh. In pediatric patients less than 1 year of age, pinch the thigh muscle while administering EVZIO. - Upon actuation, EVZIO automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone, and retracts the needle fully into its housing. The needle is not visible before, during, or after injection. - Each EVZIO can only be used one time. - If the electronic voice instruction system on EVZIO does not work properly, EVZIO will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on its label. - The electronic voice instructions are independent of activating EVZIO and are not required to wait for the voice instructions to be completed prior to moving to the next step in the injection process. - Post-injection, the black base locks in place, a red indicator appears in the viewing window and electronic visual and audible instructions signal that EVZIO has delivered the intended dose of naloxone hydrochloride. - EVZIO’s red safety guard should not be replaced under any circumstances. However, the Trainer is designed for re-use and its red safety guard can be removed and replaced. - It is recommended that patients and caregivers become familiar with the training device provided and read the Instructions for Use; however, untrained caregivers or family members should still attempt to use EVZIO during a suspected opioid overdose while awaiting definitive emergency medical care. - Periodically visually inspect the naloxone solution through the viewing window. If the solution is discolored, cloudy, or contains solid particles, replace it with a new EVZIO. - Replace EVZIO before its expiration date. # Precautions with Alcohol - Alcohol-Naloxone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - EVZIO® # Look-Alike Drug Names - naloxone® — Lanoxin® - Narcan® — Norcuron® # Drug Shortage Status # Price	Naloxone Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, 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. # Overview Naloxone is an opioid antagonist that is FDA approved for the treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Common adverse reactions include hypotension, hypertension, ventricular tachycardia, ventricular fibrillation, dyspnea, pulmonary edema, cardiac arrest, death, coma, and encephalopathy. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. - Naloxone is intended for immediate administration as emergency therapy in settings where opioids may be present. - Naloxone is not a substitute for emergency medical care. - Administer the initial dose of Naloxone to adult intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary, and seek emergency medical assistance. Administer Naloxone as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. The requirement for repeat doses of Naloxone depends upon the amount, type, and route of administration of the opioid being antagonized. - If the desired response is not obtained after 2 or 3 minutes, another Naloxone dose may be administered. If there is still no response and additional doses are available, additional Naloxone doses may be administered every 2 to 3 minutes until emergency medical assistance arrives. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. - Injection: 0.4 mg/0.4 mL naloxone hydrochloride solution in a pre-filled auto-injector. Each Naloxone delivers 0.4 mg naloxone hydrochloride injection (0.4 mL). ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Naloxone in adult patients. ### Non–Guideline-Supported Use - Naloxone 20 mg or 40 mg.[1] # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) - Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. - Naloxone is intended for immediate administration as emergency therapy in settings where opioids may be present. - Naloxone is not a substitute for emergency medical care. - Administer the initial dose of Naloxone to pediatric patients intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary, and seek emergency medical assistance. Administer Naloxone as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. The requirement for repeat doses of Naloxone depends upon the amount, type, and route of administration of the opioid being antagonized. - If the desired response is not obtained after 2 or 3 minutes, another Naloxone dose may be administered. If there is still no response and additional doses are available, additional Naloxone doses may be administered every 2 to 3 minutes until emergency medical assistance arrives. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. - In pediatric patients under the age of one, the caregiver should pinch the thigh muscle while administering Naloxone. - Injection: 0.4 mg/0.4 mL naloxone hydrochloride solution in a pre-filled auto-injector. Each Naloxone delivers 0.4 mg naloxone hydrochloride injection (0.4 mL). ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Naloxone in pediatric patients. ### Non–Guideline-Supported Use - Naloxone 0.05 mg IM.[2] # Contraindications - Naloxone is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients. # Warnings ### Precautions - Duration of Effect - The duration of action of most opioids is likely to exceed that of Naloxone resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek immediate emergency medical assistance after delivering the first dose of Naloxone, keep the patient under continued surveillance, and repeat doses of Naloxone as necessary. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. - Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists - Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. Large doses of naloxone hydrochloride are required to antagonize buprenorphine because the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression. - Precipitation of Severe Opioid Withdrawal - The use of Naloxone in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. - Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. These events have occurred in patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, after use of naloxone hydrochloride, patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects should be monitored for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting. It has been suggested that the pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures. # Adverse Reactions ## Clinical Trials Experience - The following adverse reactions have been identified during post-approval use of naloxone hydrochloride in the post-operative setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia and have caused agitation. - Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, hyperactive reflexes. ## Postmarketing Experience There is limited information regarding Postmarketing Experience of Naloxone in the drug label. # Drug Interactions There is limited information regarding Naloxone Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): - Pregnancy Category B - Risk Summary - There are no adequate and well-controlled studies with Naloxone in pregnant women. Animal studies were conducted with naloxone hydrochloride given during organogenesis in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day. These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Because animal reproduction studies are not always predictive of human response, Naloxone should be used during pregnancy only if clearly needed. - Clinical Considerations - Naloxone hydrochloride crosses the placenta, and may precipitate withdrawal in the fetus as well as in the opioid-dependent mother. The fetus should be evaluated for signs of distress after Naloxone is used. Careful monitoring is needed until the fetus and mother are stabilized. - Data - Animal Data - Naloxone hydrochloride was administered during organogenesis to mice and rats at doses 4-times and 8-times, respectively, the dose of 10 mg/day given to a 50 kg human (when based on body surface area or mg/m2). These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Pregnancy Category (AUS): - Australian Drug Evaluation Committee (ADEC) Pregnancy Category There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Naloxone in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Naloxone during labor and delivery. ### Nursing Mothers - It is not known whether naloxone hydrochloride is present in human milk. Because many drugs are present in human milk, exercise caution when Naloxone is administered to a nursing woman. ### Pediatric Use - The safety and effectiveness of Naloxone (for intramuscular and subcutaneous use) have been established in pediatric patients for known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Use of naloxone hydrochloride in pediatric patients is supported by evidence from adequate and well-controlled studies of naloxone hydrochloride in adults with additional data from 15 clinical studies (controlled and uncontrolled) in which neonates and pediatric patients received parenteral naloxone in doses ranging from 0.005 mg/kg to 0.01 mg/kg. Safety and effectiveness are also supported by use of other naloxone hydrochloride products in the post-marketing setting as well as data available in the medical literature and clinical practice guidelines. - Absorption of naloxone hydrochloride following subcutaneous or intramuscular administration in pediatric patients may be erratic or delayed. Even when the opiate-intoxicated pediatric patient responds dramatically to naloxone hydrochloride injection, he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized. In opioid-dependent pediatric patients, (including neonates), administration of naloxone may result in an abrupt and complete reversal of opioid effects, precipitating an acute opioid withdrawal syndrome. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts. - In neonates and pediatric patients less than 1 year of age, careful observation of the administration site for evidence of residual needle parts and/or signs of infection is warranted. ### Geriatic Use - Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Therefore, the systemic exposure of naloxone can be higher in these patients. - Clinical studies of naloxone hydrochloride did not include sufficient numbers 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. ### Gender There is no FDA guidance on the use of Naloxone with respect to specific gender populations. ### Race There is no FDA guidance on the use of Naloxone with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Naloxone in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Naloxone in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Naloxone in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Naloxone in patients who are immunocompromised. # Administration and Monitoring ### Administration - Intramuscular - Subcutaneous ### Monitoring There is limited information regarding Monitoring of Naloxone in the drug label. # IV Compatibility There is limited information regarding IV Compatibility of Naloxone in the drug label. # Overdosage ## Chronic Overdose There is limited information regarding Chronic Overdose of Naloxone in the drug label. # Pharmacology ## Mechanism of Action - Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. - Naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine. ## Structure - Naloxone (naloxone hydrochloride injection, USP) is a pre-filled, single-use auto-injector. Naloxone is not made with natural rubber latex. Chemically, naloxone hydrochloride is the hydrochloride salt of 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride with the following structure: - Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. - Each 0.4 mL in Naloxone contains inactive ingredients of 3.34 mg of sodium chloride, hydrochloric acid to adjust pH, and water for injection. The pH range is 3.0 to 4.5. ## Pharmacodynamics - When naloxone hydrochloride is administered intravenously, the onset of action is generally apparent within two minutes. The time to onset of action is shorter for intravenous compared to subcutaneous or intramuscular routes of administration. - The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. ## Pharmacokinetics - In one pharmacokinetic study in 30 healthy subjects, a single 0.4 mg subcutaneous or intramuscular naloxone injection administered using Naloxone provides equivalent naloxone AUC and 15% greater naloxone Cmax in comparison to a single 0.4 mg subcutaneous or intramuscular naloxone injection administered using a standard syringe. - Following a single Naloxone injection, the median Tmax of naloxone was reached at 15 minutes (range 5 minutes to 1.2 hours), with a mean (± SD) Cmax value of 1.24 (± 0.64) ng/mL. The mean (± SD) plasma half-life of naloxone in healthy adults was 1.28 (± 0.48) hours. In the same study, following administration of a single dose of 0.4 mg naloxone injection using a standard syringe, the median Tmax was 20 minutes (range 5 minutes to 2.03 hours) and the mean (± SD) Cmax value was 1.07 (± 0.48) ng/mL. The mean (± SD) plasma half-life was 1.36 (± 0.32) hours. - Distribution - Following parenteral administration, naloxone is distributed in the body and readily crosses the placenta. Plasma protein binding occurs but is relatively weak. Plasma albumin is the major binding constituent but significant binding of naloxone also occurs to plasma constituents other than albumin. It is not known whether naloxone is excreted into human milk. - Metabolism - Naloxone hydrochloride is metabolized in the liver, primarily by glucuronide conjugation with naloxone-3-glucoronide as the major metabolite. - Elimination - After an oral or intravenous dose, about 25-40% of naloxone is excreted as metabolites in urine within 6 hours, about 50% in 24 hours, and 60-70% in 72 hours. Following a single Naloxone injection, the mean (± SD) plasma half-life of naloxone in healthy adults was 1.28 (± 0.48) hours. In a neonatal study of naloxone injection, the mean (± SD) plasma half-life was observed to be 3.1 (± 0.5) hours. ## Nonclinical Toxicology - Carcinogenesis - Long-term animal studies to evaluate the carcinogenic potential of naloxone have not been completed. - Mutagenesis - Naloxone was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. - Impairment of Fertility - Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no adverse effect of naloxone hydrochloride on fertility. # Clinical Studies There is limited information regarding Clinical Studies of Naloxone in the drug label. # How Supplied - Carton containing two Naloxone (naloxone hydrochloride injection, USP) 0.4 mg auto-injectors and a single Trainer for Naloxone - NDC 60842-030-01 - Storage and Handling - Store Naloxone in the outer case provided. - Store at controlled room temperature 15°C to 25°C (59°F to 77°F) excursions permitted between 4°C and 40°C (between 39°F and 104°F). - Before using, check to make sure the solution in the auto-injector is not discolored. Replace Naloxone if the solution is discolored or contains a precipitate. ## Storage There is limited information regarding Naloxone Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information - Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Instructions for Use). - Instruct patients and their family members or caregivers to: - Become familiar with the following information contained in the carton as soon as they receive EVZIO: EVZIO Instructions for Use Trainer for EVZIO Instructions for Use Trainer for EVZIO - EVZIO Instructions for Use - Trainer for EVZIO Instructions for Use - Trainer for EVZIO - Practice using the Trainer before EVZIO is needed. Each EVZIO (which is purple and yellow) can only be used one time; however, the Trainer (which is black and white) can be re-used for training purposes and its red safety guard can be removed and replaced. Both EVZIO and the Trainer for EVZIO incorporate the electronic voice instruction system. - Each EVZIO (which is purple and yellow) can only be used one time; however, the Trainer (which is black and white) can be re-used for training purposes and its red safety guard can be removed and replaced. - Both EVZIO and the Trainer for EVZIO incorporate the electronic voice instruction system. - Make sure EVZIO is present whenever persons may be intentionally or accidentally exposed to an opioid to treat serious opioid overdose (i.e., opioid emergencies). - Instruct the patients and their family members or caregivers how to recognize the signs and symptoms of an opioid overdose requiring the use of EVZIO such as the following: - Extreme sleepiness - inability to awaken a patient verbally or upon a firm sternal rub. - Breathing problems - this can range from slow or shallow breathing to no breathing in a patient who cannot be awakened. - Other signs and symptoms that may accompany sleepiness and breathing problems include the following: - Extremely small pupils (the black circle in the center of the colored part of the eye) sometimes called “pinpoint pupils.” - Slow heartbeat and/or low blood pressure. - Instruct them that when in doubt, if a patient is unresponsive, and an opioid overdose is suspected, administer EVZIO as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. Instruct them to seek emergency medical assistance after administering the first dose of EVZIO. - Duration of Effect - Instruct patients and their family members or caregivers that since the duration of action of most opioids may exceed that of naloxone, seek immediate emergency medical assistance, keep the patient under continued surveillance, and administer repeated doses of EVZIO as necessary. - Limited Efficacy for/with Partial Agonists or Mixed Agonist/Antagonists - Instruct patients and their family members or caregivers that the reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. - Precipitation of Severe Opioid Withdrawal - Instruct patients and their family members or caregivers that the use of EVZIO in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life threatening if not recognized and properly treated, and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. - Administration Instructions - Instruct patients and their family members or caregivers about the following important information: EVZIO is user actuated and may be administered through clothing [e.g., pants, jeans, etc.] if necessary. Inject EVZIO while pressing into the anterolateral aspect of the thigh. In pediatric patients less than 1 year of age, pinch the thigh muscle while administering EVZIO. Upon actuation, EVZIO automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone, and retracts the needle fully into its housing. The needle is not visible before, during, or after injection. Each EVZIO can only be used one time. If the electronic voice instruction system on EVZIO does not work properly, EVZIO will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on its label. The electronic voice instructions are independent of activating EVZIO and are not required to wait for the voice instructions to be completed prior to moving to the next step in the injection process. Post-injection, the black base locks in place, a red indicator appears in the viewing window and electronic visual and audible instructions signal that EVZIO has delivered the intended dose of naloxone hydrochloride. EVZIO’s red safety guard should not be replaced under any circumstances. However, the Trainer is designed for re-use and its red safety guard can be removed and replaced. It is recommended that patients and caregivers become familiar with the training device provided and read the Instructions for Use; however, untrained caregivers or family members should still attempt to use EVZIO during a suspected opioid overdose while awaiting definitive emergency medical care. Periodically visually inspect the naloxone solution through the viewing window. If the solution is discolored, cloudy, or contains solid particles, replace it with a new EVZIO. Replace EVZIO before its expiration date. - EVZIO is user actuated and may be administered through clothing [e.g., pants, jeans, etc.] if necessary. - Inject EVZIO while pressing into the anterolateral aspect of the thigh. In pediatric patients less than 1 year of age, pinch the thigh muscle while administering EVZIO. - Upon actuation, EVZIO automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone, and retracts the needle fully into its housing. The needle is not visible before, during, or after injection. - Each EVZIO can only be used one time. - If the electronic voice instruction system on EVZIO does not work properly, EVZIO will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on its label. - The electronic voice instructions are independent of activating EVZIO and are not required to wait for the voice instructions to be completed prior to moving to the next step in the injection process. - Post-injection, the black base locks in place, a red indicator appears in the viewing window and electronic visual and audible instructions signal that EVZIO has delivered the intended dose of naloxone hydrochloride. - EVZIO’s red safety guard should not be replaced under any circumstances. However, the Trainer is designed for re-use and its red safety guard can be removed and replaced. - It is recommended that patients and caregivers become familiar with the training device provided and read the Instructions for Use; however, untrained caregivers or family members should still attempt to use EVZIO during a suspected opioid overdose while awaiting definitive emergency medical care. - Periodically visually inspect the naloxone solution through the viewing window. If the solution is discolored, cloudy, or contains solid particles, replace it with a new EVZIO. - Replace EVZIO before its expiration date. # Precautions with Alcohol - Alcohol-Naloxone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - EVZIO®[3] # Look-Alike Drug Names - naloxone® — Lanoxin®[4] - Narcan® — Norcuron®[4] # Drug Shortage Status # Price	https://www.wikidoc.org/index.php/Naloxone
134a58e833c2da20dc8c4872e0702626d7cad1c1	wikidoc	Narcotic	Narcotic # Background The term narcotic (ναρκωτικός) is believed to have been coined by Galen to refer to agents that benumb or deaden, causing loss of feeling or paralysis. The term is based on the Greek word ναρκωσις (narcosis), the term used by Hippocrates for the process of benumbing or the benumbed state. Galen listed mandrake root, altercus (eclata) seeds, and poppy juice (i.e. opium) as the chief examples. In U.S. legal context, narcotic refers to opium, opium derivatives, and their semi-synthetic or fully synthetic substitutes "as well as cocaine and coca leaves," which although classified as "narcotics" in the U.S. Controlled Substances Act (CSA), are chemically not narcotics. Contrary to popular belief, marijuana is not a narcotic. Neither are LSD and other psychedelic drugs. Many law enforcement officials in the United States inaccurately use the word "narcotic" to refer to any illegal drug or any unlawfully possessed drug. An example is referring to cannabis as a narcotic. Because the term is often used broadly, inaccurately or pejoratively outside medical contexts, most medical professionals prefer the more precise term opioid, which refers to natural, semi-synthetic and synthetic substances that behave pharmacologically like morphine, the primary active constituent of natural opium poppy. # Administration Narcotics can be administered in a variety of ways. In a medical context, they are taken orally, transdermally (skin patches), injected, or administered as suppositories. As recreational drugs, they may be used orally, but are also commonly smoked, snorted, or self-administered by the more direct routes of subcutaneous ("skin popping") and intravenous ("mainlining") injection, depending on the precise substance in question. (Recreational use of suppositories is uncommon.) # Effects Drug effects depend heavily on the dose, route of administration, previous exposure to the drug, and the expectation of the user. Aside from their clinical use in the treatment of pain, cough, and acute diarrhea, narcotics produce a general sense of well-being, known as euphoria, and reduce tension, anxiety, and aggression. These effects are helpful in a therapeutic setting and contribute to their popularity as recreational drugs, as well as helping to produce dependency. Narcotic use is associated with a variety of side effects, including drowsiness, itching, sleeplessness, inability to concentrate, apathy, lessened physical activity, constriction of the pupils, dilation of the subcutaneous blood vessels causing flushing of the face and neck, constipation, nausea, vomiting and, most significantly, respiratory depression. As the dose is increased, the subjective, analgesic, and toxic effects become more pronounced. Except in cases of acute intoxication, there is no loss of motor coordination or slurred speech, as occurs with many depressants such as alcohol or barbiturates. # Hazards Among the hazards of careless or excessive drug use are the increasing risk of infection, disease and overdose. Medical complications common among recreational narcotic users arise primarily from the non-sterile practices of injecting. Skin, lung and brain abscesses, endocarditis, hepatitis and HIV/AIDS are commonly found among persons with narcotic dependencies who share syringes or inhale the drug. There has been much discussion about the dangers related to the adulterants/diluents found in street drugs, such as heroin, where rumours abound about what is used to "cut" street drugs, e.g., ground glass, talcum powder, rat poison, domestic cleaning powders, and other cutting agents. Recent evidence shows that this kind of "dangerous adulteration" is largely mythical and that far less cutting of drugs than is normally assumed actually takes place. However, since there is no simple way to determine the purity of a drug that is sold on the street, the effects of using street narcotics are unpredictable. It remains the case that the greatest risk presented by most illicit drugs relates to the drugs themselves and how they are used, e.g., in conjunction with other drugs (alcohol is a particularly risky drug to use whilst also using other street drugs), in excess (most recreational and non-excessive drug use does not result in harm), and how a drug is administered (such as the sharing of needles). HIV and hepatitis infection rates drop among opioid injectors who have access to clean syringes and take advantage of that provision. # Tolerance and dependence With repeated use of narcotics, tolerance and dependence develop. The development of tolerance is characterized by a shortened duration and a decreased intensity of analgesia, euphoria and sedation, which creates the need to administer progressively larger doses to attain the desired effect. Tolerance does not develop uniformly for all actions of these drugs, giving rise to a number of toxic effects. Although the lethal dose is increased significantly in tolerant users, there is always a dose at which death can occur from respiratory depression. It is clear, however, that tolerance and dependence, both part of the conventional idea of addiction, are insufficient to explain in totality what addiction is. Addiction is a broader behavioural phenomenon that also encapsulates nonsubstance based activity (such as excessive and compulsive gambling, excessive and compulsive eating, and a range of other excessive and compulsive behaviours) that has many of the same characteristics that substance based dependency displays. Moreover, it isn't always the case that those with a physical dependency to opiates find it too difficult to get over their "addiction," because so-called medical addicts (those that become physically dependent on opiates given for pain relief after treatment) only have to "give-up" the physical symptoms - they don't also have the all important psychological and life-style attachment to the drug which goes to make up the all-encompassing "addiction." Physical dependence refers to an alteration of normal body functions that necessitates the continued presence of a drug in order to prevent the withdrawal or abstinence syndrome. The intensity and character of the physical symptoms experienced during withdrawal are directly related to the particular drug in use, the total daily dose, the interval between doses, the duration of use and the health and personality of the user. In general, narcotics with shorter durations of action tend to produce shorter, more intense withdrawal symptoms, while drugs that produce longer narcotic effects have prolonged symptoms that tend to be less severe. The withdrawal symptoms experienced from opioid addiction are usually first felt shortly before the time of the next scheduled dose. Early symptoms include watery eyes, runny nose, yawning and sweating. Restlessness, irritability, loss of appetite, tremors and severe sneezing appear as the syndrome progresses. Severe depression and vomiting are not uncommon. The heart rate and blood pressure are elevated. Chills alternating with flushing and excessive sweating are also characteristic symptoms. Pains in the bones and muscles of the back and extremities occur as do muscle spasms and kicking movements, which may be the source of the expression "kicking the habit." At any point during this process, a suitable dose of any opioid can be administered that will dramatically reverse the withdrawal symptoms. Without intervention, the syndrome will run its course and most of the overt physical symptoms will disappear within 5 to 15 days, depending on the opioid used. The psychological dependence that is associated with narcotic addiction is complex and protracted. Long after the physical need for the drug has passed, the addict may continue to think and talk about the use of drugs. There is a high probability that relapse will occur after narcotic withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. There are two major patterns of narcotic dependence seen in the United States. One involves individuals whose drug use was initiated within the context of medical treatment who escalate their dose through "doctor shopping" or branch out to illicit drugs. A very small percentage of addicts are in this group. The other more common pattern of non-medical use is initiated outside the therapeutic setting with experimental or recreational use of narcotics. The majority of individuals in this category may use narcotics sporadically for months or even years. These occasional users are called "chippers." Although they are neither tolerant of nor dependent on narcotics, the social, medical and legal consequences of their behavior can be very serious. Some experimental users will escalate their narcotic use and will eventually become dependent, both physically and psychologically. The earlier drug use begins, the more likely it is to progress to dependence. Heroin use among males in inner cities is generally initiated in adolescence, and dependence often develops in about 1 or 2 years. Signs and symptoms of narcotic/opioid overdose include the following: euphoria, arousable somnolence ("nodding"), nausea, pinpoint pupils (except with Pethidine/Meperidine ), hypoxia, or in combination with other types of drugs, coma, and seizures.	Narcotic Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Background The term narcotic (ναρκωτικός) is believed to have been coined by Galen to refer to agents that benumb or deaden, causing loss of feeling or paralysis. The term is based on the Greek word ναρκωσις (narcosis), the term used by Hippocrates for the process of benumbing or the benumbed state. Galen listed mandrake root, altercus (eclata)[1] seeds, and poppy juice (i.e. opium) as the chief examples.[2][3] In U.S. legal context, narcotic refers to opium, opium derivatives, and their semi-synthetic or fully synthetic substitutes "as well as cocaine and coca leaves," which although classified as "narcotics" in the U.S. Controlled Substances Act (CSA), are chemically not narcotics. Contrary to popular belief, marijuana is not a narcotic. Neither are LSD and other psychedelic drugs.[4] Many law enforcement officials in the United States inaccurately use the word "narcotic" to refer to any illegal drug or any unlawfully possessed drug. An example is referring to cannabis as a narcotic. Because the term is often used broadly, inaccurately or pejoratively outside medical contexts, most medical professionals prefer the more precise term opioid, which refers to natural, semi-synthetic and synthetic substances that behave pharmacologically like morphine, the primary active constituent of natural opium poppy. # Administration Narcotics can be administered in a variety of ways. In a medical context, they are taken orally, transdermally (skin patches), injected, or administered as suppositories. As recreational drugs, they may be used orally, but are also commonly smoked, snorted, or self-administered by the more direct routes of subcutaneous ("skin popping") and intravenous ("mainlining") injection, depending on the precise substance in question. (Recreational use of suppositories is uncommon.) # Effects Drug effects depend heavily on the dose, route of administration, previous exposure to the drug, and the expectation of the user. Aside from their clinical use in the treatment of pain, cough, and acute diarrhea, narcotics produce a general sense of well-being, known as euphoria, and reduce tension, anxiety, and aggression. These effects are helpful in a therapeutic setting and contribute to their popularity as recreational drugs, as well as helping to produce dependency. Narcotic use is associated with a variety of side effects, including drowsiness, itching, sleeplessness, inability to concentrate, apathy, lessened physical activity, constriction of the pupils, dilation of the subcutaneous blood vessels causing flushing of the face and neck, constipation, nausea, vomiting and, most significantly, respiratory depression. As the dose is increased, the subjective, analgesic, and toxic effects become more pronounced. Except in cases of acute intoxication, there is no loss of motor coordination or slurred speech, as occurs with many depressants such as alcohol or barbiturates. # Hazards Among the hazards of careless or excessive drug use are the increasing risk of infection, disease and overdose. Medical complications common among recreational narcotic users arise primarily from the non-sterile practices of injecting. Skin, lung and brain abscesses, endocarditis, hepatitis and HIV/AIDS are commonly found among persons with narcotic dependencies who share syringes or inhale the drug. There has been much discussion about the dangers related to the adulterants/diluents found in street drugs, such as heroin, where rumours abound about what is used to "cut" street drugs, e.g., ground glass, talcum powder, rat poison, domestic cleaning powders, and other cutting agents. Recent evidence shows that this kind of "dangerous adulteration" is largely mythical and that far less cutting of drugs than is normally assumed actually takes place. However, since there is no simple way to determine the purity of a drug that is sold on the street, the effects of using street narcotics are unpredictable. It remains the case that the greatest risk presented by most illicit drugs relates to the drugs themselves and how they are used, e.g., in conjunction with other drugs (alcohol is a particularly risky drug to use whilst also using other street drugs), in excess (most recreational and non-excessive drug use does not result in harm), and how a drug is administered (such as the sharing of needles). HIV and hepatitis infection rates drop among opioid injectors who have access to clean syringes and take advantage of that provision. # Tolerance and dependence With repeated use of narcotics, tolerance and dependence develop. The development of tolerance is characterized by a shortened duration and a decreased intensity of analgesia, euphoria and sedation, which creates the need to administer progressively larger doses to attain the desired effect. Tolerance does not develop uniformly for all actions of these drugs, giving rise to a number of toxic effects. Although the lethal dose is increased significantly in tolerant users, there is always a dose at which death can occur from respiratory depression. It is clear, however, that tolerance and dependence, both part of the conventional idea of addiction, are insufficient to explain in totality what addiction is. Addiction is a broader behavioural phenomenon that also encapsulates nonsubstance based activity (such as excessive and compulsive gambling, excessive and compulsive eating, and a range of other excessive and compulsive behaviours) that has many of the same characteristics that substance based dependency displays. Moreover, it isn't always the case that those with a physical dependency to opiates find it too difficult to get over their "addiction," because so-called medical addicts (those that become physically dependent on opiates given for pain relief after treatment) only have to "give-up" the physical symptoms - they don't also have the all important psychological and life-style attachment to the drug which goes to make up the all-encompassing "addiction." Physical dependence refers to an alteration of normal body functions that necessitates the continued presence of a drug in order to prevent the withdrawal or abstinence syndrome. The intensity and character of the physical symptoms experienced during withdrawal are directly related to the particular drug in use, the total daily dose, the interval between doses, the duration of use and the health and personality of the user. In general, narcotics with shorter durations of action tend to produce shorter, more intense withdrawal symptoms, while drugs that produce longer narcotic effects have prolonged symptoms that tend to be less severe. The withdrawal symptoms experienced from opioid addiction are usually first felt shortly before the time of the next scheduled dose. Early symptoms include watery eyes, runny nose, yawning and sweating. Restlessness, irritability, loss of appetite, tremors and severe sneezing appear as the syndrome progresses. Severe depression and vomiting are not uncommon. The heart rate and blood pressure are elevated. Chills alternating with flushing and excessive sweating are also characteristic symptoms. Pains in the bones and muscles of the back and extremities occur as do muscle spasms and kicking movements, which may be the source of the expression "kicking the habit." At any point during this process, a suitable dose of any opioid can be administered that will dramatically reverse the withdrawal symptoms. Without intervention, the syndrome will run its course and most of the overt physical symptoms will disappear within 5 to 15 days, depending on the opioid used. The psychological dependence that is associated with narcotic addiction is complex and protracted. Long after the physical need for the drug has passed, the addict may continue to think and talk about the use of drugs. There is a high probability that relapse will occur after narcotic withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. There are two major patterns of narcotic dependence seen in the United States. One involves individuals whose drug use was initiated within the context of medical treatment who escalate their dose through "doctor shopping" or branch out to illicit drugs. A very small percentage of addicts are in this group. The other more common pattern of non-medical use is initiated outside the therapeutic setting with experimental or recreational use of narcotics. The majority of individuals in this category may use narcotics sporadically for months or even years. These occasional users are called "chippers." Although they are neither tolerant of nor dependent on narcotics, the social, medical and legal consequences of their behavior can be very serious. Some experimental users will escalate their narcotic use and will eventually become dependent, both physically and psychologically. The earlier drug use begins, the more likely it is to progress to dependence. Heroin use among males in inner cities is generally initiated in adolescence, and dependence often develops in about 1 or 2 years. Signs and symptoms of narcotic/opioid overdose include the following: euphoria, arousable somnolence ("nodding"), nausea, pinpoint pupils (except with Pethidine/Meperidine [Demerol]), hypoxia, or in combination with other types of drugs, coma, and seizures.	https://www.wikidoc.org/index.php/Narcotic
7cf7ded09d32f65486bcc89d94b22606d11bdaa5	wikidoc	Neem oil	Neem oil Neem oil is a vegetable oil pressed from the fruits and seeds of Neem (Azadirachta indica), an evergreen tree which is endemic to the Indian sub-continent and has been introduced to many other areas in the tropics. It is perhaps the most important of the commercially available products of neem. # Characteristics Neem oil is generally light to dark brown, bitter and has a rather strong odour that is said to combine the odours of peanut and garlic. It comprises mainly triglycerides and large amounts of triterpenoid compounds, which are responsible for the bitter taste. It is hydrophobic in nature and in order to emulsify it in water for application purposes, it must be formulated with appropriate surfactants. Neem oil also contains steroids (campesterol, beta-sitosterol, stigmasterol) and a plethora of triterpenoids of which Azadirachtin is the most well known and studied. The Azadirachtin content of Neem Oil varies from 300ppm to over 2000ppm depending on the quality of the neem seeds crushed. # Uses Neem oil is not used for cooking purposes but, in India and Bangladesh, it is used for preparing cosmetics (soap, hair products, body hygiene creams, hand creams) and in Ayurvedic, Unani and folklore traditional medicine, in the treatment of a wide range of afflictions. The most frequently reported indications in ancient Ayurvedic writings are skin diseases, inflammations and fevers, and more recently rheumatic disorders, insect repellent and insecticide effects. Traditional Ayurvedic uses of neem include the treatment of fever, leprosy, malaria, ophthalmia and tuberculosis. Various folk remedies for neem include use as an anthelmintic, antifeedant, antiseptic, diuretic, emmenagogue, contraceptive, febrifuge, parasiticide, pediculocide and insecticide. It has been used in traditional medicine for the treatment of tetanus, urticaria, eczema, scrofula and erysipelas. Traditional routes of administration of neem extracts included oral, vaginal and topical use. Neem oil has an extensive history of human use in India and surrounding regions for a variety of therapeutic purposes. Puri (1999) has given an account of traditional uses and therapeutic indications and pharmacological studies of this oil, in his book on neem.	Neem oil Neem oil is a vegetable oil pressed from the fruits and seeds of Neem (Azadirachta indica), an evergreen tree which is endemic to the Indian sub-continent and has been introduced to many other areas in the tropics. It is perhaps the most important of the commercially available products of neem. # Characteristics Neem oil is generally light to dark brown, bitter and has a rather strong odour that is said to combine the odours of peanut and garlic. It comprises mainly triglycerides and large amounts of triterpenoid compounds, which are responsible for the bitter taste. It is hydrophobic in nature and in order to emulsify it in water for application purposes, it must be formulated with appropriate surfactants. Neem oil also contains steroids (campesterol, beta-sitosterol, stigmasterol) and a plethora of triterpenoids of which Azadirachtin is the most well known and studied. The Azadirachtin content of Neem Oil varies from 300ppm to over 2000ppm depending on the quality of the neem seeds crushed. # Uses Neem oil is not used for cooking purposes but, in India and Bangladesh, it is used for preparing cosmetics (soap, hair products, body hygiene creams, hand creams) and in Ayurvedic, Unani and folklore traditional medicine, in the treatment of a wide range of afflictions. The most frequently reported indications in ancient Ayurvedic writings are skin diseases, inflammations and fevers, and more recently rheumatic disorders, insect repellent and insecticide effects.[1] Traditional Ayurvedic uses of neem include the treatment of fever, leprosy, malaria, ophthalmia and tuberculosis. Various folk remedies for neem include use as an anthelmintic, antifeedant, antiseptic, diuretic, emmenagogue, contraceptive, febrifuge, parasiticide, pediculocide and insecticide. It has been used in traditional medicine for the treatment of tetanus, urticaria, eczema, scrofula and erysipelas. Traditional routes of administration of neem extracts included oral, vaginal and topical use. Neem oil has an extensive history of human use in India and surrounding regions for a variety of therapeutic purposes. Puri (1999) has given an account of traditional uses and therapeutic indications and pharmacological studies of this oil, in his book on neem.	https://www.wikidoc.org/index.php/Neem_Seed_Oil
2441289ede4b35ff19b6078077cd955d83bb6c79	wikidoc	Neoplasm	Neoplasm # Overview Neoplasia (new growth in Greek) is the abnormal proliferation of cells, resulting in a neoplasm. Neoplasia is the scientific term for the group of diseases commonly called tumor or cancer. Because neoplasia includes very different diseases, it is difficult to find a definition that describe them all. The definition of the British oncologist R.A. Willis is widely cited: A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues, and persists in the same excessive manner after cessation of the stimulus which evoked the change. # Types A neoplasm can be benign, potentially malignant (pre-cancer) or malignant (cancer). - Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They do not transform into cancer. - Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer. - Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host. # Difficulty of definition A precise and all-encompassing definition of neoplasm has proven elusive. A neoplasm has been defined as an uncontrolled and progressive growth, although this definition is criticized because some neoplasms, such as nevi, are not progressive. Some sources consider a neoplasm to be synonymous with a tumor or unusual mass of tissue. This is criticized because many neoplasms form no mass, including cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and leukemia. # Biological properties of neoplastic cells The structure of a neoplasm is less organized than that of the surrounding tissue. ## Clonality Neoplastic tumors often contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are usually presumed to be clonal - that is, they are descended from a single progenitor cell. The neoplastic cells typically bear common genetic or epigenetic abnormalities, an evidence of clonality. For some types of neoplasm, e.g. lymphoma and leukemia, the demonstration of clonality is now considered to be necessary (though not sufficient) to define a cellular proliferation as neoplastic.	Neoplasm Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Neoplasia (new growth in Greek) is the abnormal proliferation of cells, resulting in a neoplasm. [1] [2] Neoplasia is the scientific term for the group of diseases commonly called tumor or cancer. [3] Because neoplasia includes very different diseases, it is difficult to find a definition that describe them all. The definition of the British oncologist R.A. Willis is widely cited: A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues, and persists in the same excessive manner after cessation of the stimulus which evoked the change. # Types A neoplasm can be benign, potentially malignant (pre-cancer) or malignant (cancer). [5] - Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They do not transform into cancer. - Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer. - Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host. # Difficulty of definition A precise and all-encompassing definition of neoplasm has proven elusive. A neoplasm has been defined as an uncontrolled and progressive growth, although this definition is criticized because some neoplasms, such as nevi, are not progressive.[6] Some sources consider a neoplasm to be synonymous with a tumor or unusual mass of tissue.[3] This is criticized because many neoplasms form no mass, including cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and leukemia. # Biological properties of neoplastic cells The structure of a neoplasm is less organized than that of the surrounding tissue.[7] ## Clonality Neoplastic tumors often contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are usually presumed to be clonal - that is, they are descended from a single progenitor cell. The neoplastic cells typically bear common genetic or epigenetic abnormalities, an evidence of clonality. For some types of neoplasm, e.g. lymphoma and leukemia, the demonstration of clonality is now considered to be necessary (though not sufficient) to define a cellular proliferation as neoplastic.[8]	https://www.wikidoc.org/index.php/Neoplasias
012b2f3bd3428317d211094aaf63181348ae316c	wikidoc	Nepenthe	Nepenthe Nepenthe is a drug of forgetfulness mentioned in Greek mythology, depicted as originating in Egypt. The word "Nepenthe" first appears in the fourth book (vv. 220-221) of the Odyssey of Homer. Literally, it means "the one that chases away sorrow" (ne = not, penthos = grief, sorrow). In the Odyssey, "Nepenthes pharmakon" (i.e. a philter that chases away sorrow) is a magical potion given to Helen by an Egyptian queen. It quells all sorrows with forgetfulness. Many scholars think that nepenthe might have been an opium preparation, perhaps similar to laudanum . Alternatively, some believe it could have been an Egyptian wormwood elixir. (Refer to absinthe, history.) However, the descriptions in literature of the effects of nepenthe are similar to how the effects of opiates are described. The carnivorous plant genus Nepenthes is named after the drug nepenthe. # Later references - In Edmund Spenser's The Faerie Queene, book 4, canto 3, the effect of the drink is extended: "such as drinck, eternall happinesse do fynd" (verse 43). Spenser likens Nepenthe to the magic potion from Ariosto's Orlando furioso. - George Chapman refers to Nepenthe in Ovid's Banquet of Sense, stanza 10, line 1: "Sacred Nepenthe, purgatiue of care". - In Milton's Comus, lines 675-8, Comus says of his julep that "Not that Nepenthes which the wife of Thone/In Egypt gave to Jove-born Helena /Is of such power to stir up joy as this". - Alexander Pope made the reference "Lulled with the sweet nepenthe of a court" in his poem An Essay on Man. - In The Raven, a poem by Edgar Allan Poe there is a reference to "quaffing nepenthe" in order to forget a lost love: "Quaff, oh quaff this kind nepenthe, and forget this lost Lenore!". - H. P. Lovecraft referenced nepenthe in one of the famous final lines from his story "The Outsider": "For although nepenthe has calmed me, I know always that I am an outsider..." - American death metal band Nile mentions Nepenthe in their song Beneath Eternal Oceans of Sand from their first album Amongst the Catacombs of Nephren-Ka: "In the cosmos / There is balm as well as bitterness / And that balm is Nepenthe". The song is inspired by Lovecraft's short story. - Nepenthe is also the name of a collection of poetry published in 1921 by Greek poet Kostas Karyotakis. It was his second collection. - Nepenthe Productions was a production company name used by Martin Rosen for several films he directed, two of them (Watership Down and The Plague Dogs) adaptations of Richard Adams novels. - When the Spacer woman Gladia Delmarre makes love to the detective Elijah Baley in Isaac Asimov's science fiction novel The Robots of Dawn, the exhausted Bailey finds "this utterly soft end of a hard day... as soporific as the fabled nepenthe...." - In Alan Moore's graphic novel Watchmen, Sally Jupiter (the Silk Spectre) lives in a retirement home named Nepenthe Gardens, an allusion to the painful romantic relationships of her past. - In Mystery Science Theater 3000 episode 901 'The Projected Man,' nepenthe is used (somewhat satirically) to describe a plea from ghosts: Observer: "I'm sensing the presence of several disembodied souls… wandering these dark halls in search of surcease, an end to their endless night… a howl of quiet desperation… towards an indifferent universe. Nepenthe! Nepenthe!" - Nepenthe is a restaurant in Big Sur, known for its views of the rugged coastline. An eponymous track on the Mannheim Steamroller album Fresh Aire VI was inspired by the view from this restaurant. - In Patricia McKillip's novel Alphabet of Thorn, Nepenthe is the main character. - In the poem The Atheist World-Builder by William Oland Bourne. - "Nepenthe" is also a song by Finnish metal band Sentenced, which alludes to alcohol: "So drink to forget, and drown all your sorrow, ..." - The Nepenthes is a song by the Japanese rock band L'Arc~en~Ciel - In chapter 4 of Nathaniel Hawthorne's novel, The Scarlet Letter, Roger Chillingworth claims, "I know not Lethe nor Nepenthe." - Nepenthe is mentioned in George Arnold's poem Wool-Gathering. - Nepente is also the name of a wine produced in the town named Oliena, in Sardinia. - In Kurt Wimmer's 2002 science-fiction film Equilibrium, Nepenthe is used by Father to describe Prozium, the drug used to quell emotion. "Prozium -- the great nepenthe. Opiate of our masses. Glue of our great society. Salve and salvation, it has delivered us from pathos, from sorrow, the deepest chasms of melancholy and hate. With it, we anesthetize grief, annihilate jealousy, obliterate rage. That those sister impulses towards joy, love, and elation are anesthetized in stride, we accept as fair sacrifice. For we embrace Prozium in its unifying fullness and all that it has done to make us great." - Nepenthe is also the fictional name of the island in Norman Douglas' novel South Wind. - Lines 358-359 of Percy Bysshe Shelley's "The Triumph of Life" read: "In her right hand she bore a crystal glass/ Mantling with bright Nepenthe". - In the song "Calgone" on the album S.C.I.E.N.C.E. by Incubus, the second verse ends with the line "Come sail aboard S.S. Nepenthe!" - Songwriter Jimmy Webb (MacArthur Park, By The Time I get to Phoenix, Worst That could Happen) mostly wrote about one lost love. A song on the Webb-produced "Magic Garden" album by the Fifth Dimension contains a song called "Dream, Pax, Nepenthe", a bittersweet memory of a time they were together. A southern California resident, Webb may also have referenced the The Big Sur restaurant. - In A Life of Learning, American Council of Learned Societies Occasional Paper No. 17 (Charles Homer Haskins Lecture for 1991), Milton Babbitt noted "the subsequent and continuing triumph of what Nelson Goodman has called the Tingle-Immersion theory, which—when applied to music—demands that music be anyone’s anodyne, a non-habit forming nepenthe." - Nepenthean Music is the publishing company of jazz pianist and composer Michael Weiss - Erasmus mentions Nepenthe in the opening paragraphs of In Praise of Folly. - Pliny makes reference to Nepenthe.	Nepenthe Nepenthe is a drug of forgetfulness mentioned in Greek mythology, depicted as originating in Egypt. The word "Nepenthe" first appears in the fourth book (vv. 220-221) of the Odyssey of Homer. Literally, it means "the one that chases away sorrow" (ne = not, penthos = grief, sorrow). In the Odyssey, "Nepenthes pharmakon" (i.e. a philter that chases away sorrow) is a magical potion given to Helen by an Egyptian queen. It quells all sorrows with forgetfulness. Many scholars think that nepenthe might have been an opium preparation, perhaps similar to laudanum [1]. Alternatively, some believe it could have been an Egyptian wormwood elixir. (Refer to absinthe, history.) However, the descriptions in literature of the effects of nepenthe are similar to how the effects of opiates are described. The carnivorous plant genus Nepenthes is named after the drug nepenthe. # Later references Template:Copyedit - In Edmund Spenser's The Faerie Queene, book 4, canto 3, the effect of the drink is extended: "such as drinck, eternall happinesse do fynd" (verse 43). Spenser likens Nepenthe to the magic potion from Ariosto's Orlando furioso. - George Chapman refers to Nepenthe in Ovid's Banquet of Sense, stanza 10, line 1: "Sacred Nepenthe, purgatiue of care". - In Milton's Comus, lines 675-8, Comus says of his julep that "Not that Nepenthes which the wife of Thone/In Egypt gave to Jove-born Helena /Is of such power to stir up joy as this". - Alexander Pope made the reference "Lulled with the sweet nepenthe of a court" in his poem An Essay on Man. - In The Raven, a poem by Edgar Allan Poe there is a reference to "quaffing nepenthe" in order to forget a lost love: "Quaff, oh quaff this kind nepenthe, and forget this lost Lenore!". - H. P. Lovecraft referenced nepenthe in one of the famous final lines from his story "The Outsider": "For although nepenthe has calmed me, I know always that I am an outsider..." - American death metal band Nile mentions Nepenthe in their song Beneath Eternal Oceans of Sand from their first album Amongst the Catacombs of Nephren-Ka: "In the cosmos / There is balm as well as bitterness / And that balm is Nepenthe". The song is inspired by Lovecraft's short story. - Nepenthe is also the name of a collection of poetry published in 1921 by Greek poet Kostas Karyotakis. It was his second collection. - Nepenthe Productions was a production company name used by Martin Rosen for several films he directed, two of them (Watership Down and The Plague Dogs) adaptations of Richard Adams novels. - When the Spacer woman Gladia Delmarre makes love to the detective Elijah Baley in Isaac Asimov's science fiction novel The Robots of Dawn, the exhausted Bailey finds "this utterly soft end of a hard day... as soporific as the fabled nepenthe...." - In Alan Moore's graphic novel Watchmen, Sally Jupiter (the Silk Spectre) lives in a retirement home named Nepenthe Gardens, an allusion to the painful romantic relationships of her past. - In Mystery Science Theater 3000 episode 901 'The Projected Man,' nepenthe is used (somewhat satirically) to describe a plea from ghosts: Observer: "I'm sensing the presence of several disembodied souls… wandering these dark halls in search of surcease, an end to their endless night… a howl of quiet desperation… towards an indifferent universe. Nepenthe! Nepenthe!" - Nepenthe is a restaurant in Big Sur, known for its views of the rugged coastline. An eponymous track on the Mannheim Steamroller album Fresh Aire VI was inspired by the view from this restaurant. - In Patricia McKillip's novel Alphabet of Thorn, Nepenthe is the main character. - In the poem The Atheist World-Builder by William Oland Bourne. - "Nepenthe" is also a song by Finnish metal band Sentenced, which alludes to alcohol: "So drink to forget, and drown all your sorrow, ..." - The Nepenthes is a song by the Japanese rock band L'Arc~en~Ciel - In chapter 4 of Nathaniel Hawthorne's novel, The Scarlet Letter, Roger Chillingworth claims, "I know not Lethe nor Nepenthe." - Nepenthe is mentioned in George Arnold's poem Wool-Gathering. - Nepente is also the name of a wine produced in the town named Oliena, in Sardinia. - In Kurt Wimmer's 2002 science-fiction film Equilibrium, Nepenthe is used by Father to describe Prozium, the drug used to quell emotion. "Prozium -- the great nepenthe. Opiate of our masses. Glue of our great society. Salve and salvation, it has delivered us from pathos, from sorrow, the deepest chasms of melancholy and hate. With it, we anesthetize grief, annihilate jealousy, obliterate rage. That those sister impulses towards joy, love, and elation are anesthetized in stride, we accept as fair sacrifice. For we embrace Prozium in its unifying fullness and all that it has done to make us great." - Nepenthe is also the fictional name of the island in Norman Douglas' novel South Wind. - Lines 358-359 of Percy Bysshe Shelley's "The Triumph of Life" read: "In her right hand she bore a crystal glass/ Mantling with bright Nepenthe". - In the song "Calgone" on the album S.C.I.E.N.C.E. by Incubus, the second verse ends with the line "Come sail aboard S.S. Nepenthe!" - Songwriter Jimmy Webb (MacArthur Park, By The Time I get to Phoenix, Worst That could Happen) mostly wrote about one lost love. A song on the Webb-produced "Magic Garden" album by the Fifth Dimension contains a song called "Dream, Pax, Nepenthe", a bittersweet memory of a time they were together. A southern California resident, Webb may also have referenced the The Big Sur restaurant. - In A Life of Learning, American Council of Learned Societies Occasional Paper No. 17 (Charles Homer Haskins Lecture for 1991), Milton Babbitt noted "the subsequent and continuing triumph of what Nelson Goodman has called the Tingle-Immersion theory, which—when applied to music—demands that music be anyone’s anodyne, a non-habit forming nepenthe." - Nepenthean Music is the publishing company of jazz pianist and composer Michael Weiss - Erasmus mentions Nepenthe in the opening paragraphs of In Praise of Folly. - Pliny makes reference to Nepenthe. [1]	https://www.wikidoc.org/index.php/Nepenthe

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