Botulinum toxin - Knowledge

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muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped, and she constantly demonstrated deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report of the cosmetic use of Botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal

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muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped and she emoted with deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report on the cosmetic use of botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal

1119:. Side effects are not limited to direct paralysis, however, and can also include headaches, flu-like symptoms, and allergic reactions. Just as cosmetic treatments only last a number of months, paralysis side effects can have the same durations. At least in some cases, these effects are reported to dissipate in the weeks after treatment. Bruising at the site of injection is not a side effect of the toxin, but rather of the mode of administration, and is reported as preventable if the clinician applies pressure to the injection site; when it occurs, it is reported in specific cases to last 7–11 days. When injecting the masseter muscle of the jaw, loss of muscle function can result in a loss or reduction of power to chew solid foods. With continued high doses, the muscles can atrophy or lose strength; research has shown that those muscles rebuild after a break from Botox. 1135:

muscle spasticity in children treated for cerebral palsy. In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their ability to spread from the injection site. However, the clinical use of botulinum toxin A in cerebral palsy children has been proven to be safe with minimal side effects. Additionally, the FDA announced name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were given the generic name of onabotulinumtoxinA, Myobloc as rimabotulinumtoxinB, and Dysport retained its generic name of abobotulinumtoxinA. In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each. A similar warning was issued by

1648:, observed that blepharospasm patients who received injections around the eyes and upper face also enjoyed diminished facial glabellar lines ("frown lines" between the eyebrows). Alastair Carruthers reported that others at the time also noticed these effects and discussed the cosmetic potential of botulinum toxin. Unlike other investigators, the Carruthers did more than just talk about the possibility of using botulinum toxin cosmetically. They conducted a clinical study on otherwise normal individuals whose only concern was their eyebrow furrow. They performed their study between 1987 and 1989 and presented their results at the 1990 annual meeting of the American Society for Dermatologic Surgery. Their findings were subsequently published in 1992. 1181:. Other tests, such as brain scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can be administered. In an effort to remove contaminated food that remains in the gut, enemas or induced vomiting may be used. For wound infections, infected material may be removed surgically. Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not reverse existing nerve damage. In severe cases, mechanical respiration may be used to support people with respiratory failure. The nerve damage heals over time, generally over weeks to months. With proper treatment, the case fatality rate for botulinum poisoning can be greatly reduced. 1039: 1075:

neuromuscular blocking agent. The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines. The trials were conducted at 30 sites in the United States and Canada. Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines. Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles.

962:, otherwise known as improper eye alignment, is caused by imbalances in the actions of muscles that rotate the eyes. This condition can sometimes be relieved by weakening a muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held, so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect. 1079:

BLESS III ) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment. These trials were conducted at 31 sites in the United States and the European Union. All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows). Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching of eyelid.

525: 1683: 1629: 1205: 1446:. He also performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from the bacteria. From these he concluded that the bacteria themselves do not cause foodborne botulism, but rather produce a toxin that causes the disease after it is ingested. As a result of Kerner's and van Ermengem's research, it was thought that only contaminated meat or fish could cause botulism. This idea was refuted in 1904 when a botulism outbreak occurred in 1820: 1975: 13725: 10999: 42: 14450: 1492: 2165:(MHRA) for the treatment of ankle disability due to lower limb spasticity associated with stroke in adults. Joint motion may be restricted by severe muscle imbalance related to the syndrome, when some muscles are markedly hypertonic, and lack effective active lengthening. Injecting an overactive muscle to decrease its level of contraction can allow improved reciprocal motion, so improved ability to move and exercise. 1902:, is also available for both therapeutic and cosmetic use in the US. Lanzhou Institute of Biological Products in China manufactures a botulinum toxin type-A product; as of 2014, it was the only botulinum toxin type-A approved in China. Botulinum toxin type-A is also sold as Lantox and Prosigne on the global market. Neuronox, a botulinum toxin type-A product, was introduced by Medy-Tox of South Korea in 2009. 1315:(from several weeks to months). Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with the first letter indicating the light chain type and the latter indicating the heavy chain type. BoNT/FA received considerable attention under the name "BoNT/H", as it was mistakenly thought it could not be neutralized by any existing antitoxin. 14462: 8512: 8148: 7362: 6454: 5394: 5191: 4710: 4629: 4164: 1604:, and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility in 1980, and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner"). 1776:. It can be absorbed through the eyes, mucous membranes, respiratory tract, and non-intact skin. The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid. Evidence suggests that nerve exposure (simulated by injection of 1548:, a Swiss-American veterinary scientist, created a center at the Hooper Foundation in San Francisco, where he developed techniques for growing the organism and extracting the toxin, and conversely, for preventing organism growth and toxin production, and inactivating the toxin by heating. The California canning industry was thereby preserved. 1961:. Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, so is preventable. Infant botulism arising from consumption of honey or any other food that can carry these spores can be prevented by eliminating these foods from diets of children less than 12 months old. 4650: 2092:

J. D. and J. A. Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment. They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants

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detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested. To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay

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Standard areas for aesthetics botox injections include facial and other areas that can form fine lines and wrinkles due to every day muscle contractions and/or facial expressions such as smiling, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows,

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In the US, botox for medical purposes is usually covered by insurance if deemed medically necessary by a doctor and covers a plethora of medical problems including overactive bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in adults, cervical

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In response to the occurrence of these side effects, in 2008, the FDA notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating

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In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug because of an inability to obtain product liability insurance. People became desperate, as supplies of Botox were gradually consumed, forcing him to abandon people who would have been due for their next

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In 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As supplies became exhausted, people who had come to rely on periodic injections became desperate. For four months, as liability

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on 15 October 2010. The toxin is injected into the head and neck to treat these chronic headaches. Approval followed evidence presented to the agency from two studies funded by Allergan showing a very slight improvement in incidence of chronic migraines for those with migraines undergoing the Botox

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The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G). New types are occasionally found. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans,

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published the first complete description of the symptoms of botulism, based on extensive clinical observations and animal experiments. He concluded that the toxin develops in bad sausages under anaerobic conditions, is a biological substance, acts on the nervous system, and is lethal even in small

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Side effects from therapeutic use can be much more varied depending on the location of injection and the dose of toxin injected. In general, side effects from therapeutic use can be more serious than those that arise during cosmetic use. These can arise from paralysis of critical muscle groups and

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reported in 2000 that people who had cosmetic injections around the face reported relief from chronic headache. This was initially thought to be an indirect effect of reduced muscle tension, but the toxin is now known to inhibit release of peripheral nociceptive neurotransmitters, suppressing the

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The seven toxin serotypes (A–G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences. While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members. The A, B, and E

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LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024. It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines. The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I , BLESS II , and

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frown lines was published in 1992. This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown

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who exhibit headache characteristics consistent with: pressure perceived from outside source, shorter total duration of chronic migraines (<30 years), "detoxification" of participants with coexisting chronic daily headache due to medication overuse, and no current history of other preventive

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The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead

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DaxibotulinumtoxinA (Daxxify) was approved for medical use in the United States in September 2022. It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows). DaxibotulinumtoxinA is an acetylcholine release inhibitor and

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lines ('11's lines' between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect of up to six months or longer. Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those

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approved by Government agencies around the world" with less than one gram of raw botulinum toxin. Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin

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While botulinum toxin is generally considered safe in a clinical setting, serious side effects from its use can occur. Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles.

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The mechanism of botulinum toxin action – blocking the release of the neurotransmitter acetylcholine from nerve endings – was elucidated in the mid-20th century, and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues.

1264:(proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to 1720:

The global market for botulinum toxin products, driven by their cosmetic applications, was forecast to reach $ 2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to reach $ 4.7 billion ($ 2 billion in the US) in the same timeframe.

2010:. The organism is also susceptible to high salt, high oxygen, and low pH levels. The toxin itself is rapidly destroyed by heat, such as in thorough cooking. The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time. 3899:

Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, et al. (October 2011). "Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)".

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muscles, resulting in the smoothing of the overlying skin. Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection. Muscles can be treated repeatedly to maintain the smoothed appearance.

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amounts. Kerner hypothesized that this "sausage toxin" could be used to treat a variety of diseases caused by an overactive nervous system, making him the first to suggest that it could be used therapeutically. In 1870, the German physician Müller coined the term

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Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, et al. (June 2010). "OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program".

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lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials. Well before this, the cosmetic use of botulinum toxin type A became widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US

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and strabismus. Side effects in treatment of this condition were deemed to be rare, mild and treatable. The beneficial effects of the injection lasted only four to six months. Thus, blepharospasm patients required re-injection two or three times a year.

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Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA), Dysport/Azzalure (abobotulinumtoxinA), Letybo (letibotulinumtoxinA), Myobloc (rimabotulinumtoxinB), Xeomin/Bocouture (incobotulinumtoxinA), and Jeuveau (prabotulinumtoxinA).

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that occurred at a funeral where people ate pickled and smoked ham; three of them died. By examining the contaminated ham and performing autopsies on the people who died after eating it, van Ermengem isolated an anaerobic microorganism that he called

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In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A US supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25

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Based on data from thousands of people collected by 240 investigators, Oculinum Inc (which was soon acquired by Allergan) received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and

1131:, and in some cases, seizures, respiratory arrest, and death. Additionally, side effects common in cosmetic use are also common in therapeutic use, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes. 11130: 2052:

University-based ophthalmologists in the US and Canada further refined the use of botulinum toxin as a therapeutic agent. By 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of

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in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the US and other countries. LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.

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has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as

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Botox cost is generally determined by the number of units administered (avg. $ 10–30 per unit) or by the area ($ 200–1000) and depends on expertise of a physician, clinic location, number of units, and treatment complexity.

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and colleagues injected botulinum toxin into monkey extraocular muscles. The result was remarkable; a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side effects.

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injection. For a period of four months, American blepharospasm patients had to arrange to have their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.

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abobotulinumtoxinA, daxibotulinumtoxinA, daxibotulinumtoxinA-lanm, evabotulinumtoxinA, incobotulinumtoxinA, letibotulinumtoxinA, letibotulinumtoxinA-wlbg, onabotulinumtoxinA, prabotulinumtoxinA, relabotulinumtoxinA,

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the text of the labels of prescription medicines and for which medical conditions the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known as

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Botulinum toxins are among the most potent toxins known to science. Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. The estimated human

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which are widely distributed, including in soil and dust. Also, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning. Complicating the problem is that the taxonomy for

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frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by

11100: 7766: 8780:"DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Results from Each of Two Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Studies (SAKURA 1 and SAKURA 2)" 6782: 6436: 4119: 1584:, the electrical signal from an activated muscle, to guide injection) of local anesthetics as a diagnostic technique for evaluating an individual muscle's contribution to an eye movement. Because 1450:, Germany, because of canned white beans. In 1910, the German microbiologist J. Leuchs published a paper showing that the outbreaks in Ellezelles and Darmstadt were caused by different strains of 2089:

in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."

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in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."

1196:(serotypes A, B, C, D, E, F, G), which is derived from equine antibodies that have been altered to make them less immunogenic. This antitoxin is effective against all main strains of botulism. 4051: 1411:

led the authorities to issue a public warning against consuming smoked blood sausages in 1802 and to collect case reports of "sausage poisoning". Between 1817 and 1822, the German physician

11150: 1166:. In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death. 5379: 4094: 8133: 7227: 7057: 5309: 5279: 2218:

Since then, several randomized control trials have shown botulinum toxin type A to improve headache symptoms and quality of life when used prophylactically for participants with chronic

11135: 5372:"Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc)" 1291:

nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies. The light chain is a M27-family zinc

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Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. (February 2001). "Botulinum toxin as a biological weapon: medical and public health management".

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in Maryland. Carl Lamanna and James Duff developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army's

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smiles; the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of

1099:. Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion. The use of botulinum toxin A in children with 4410: 2566: 2536: 11145: 4433:"HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BOTOX® safely and effectively. See full prescribing information for BOTOX" 3269: 11028: 5302:"Follow-up to the February 8, 2008, Early Communication about an Ongoing Safety Review of Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B)" 2420: 2176:

is a condition where oral secretions are unable to be eliminated, causing pooling of saliva in the mouth. This condition can be caused by various neurological syndromes such as

4149: 2644: 7088: 11110: 11095: 11469: 11115: 7668:"Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricum type E strains" 6400: 5146: 3694: 2941: 2902: 2872: 2807: 5272:"Update of Safety Review of OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc)" 11515: 7932:

Flanders M, Tischler A, Wise J, Williams F, Beneish R, Auger N (June 1987). "Injection of type A botulinum toxin into extraocular muscles for correction of strabismus".

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M8 paper is a chemically-treated, dye-impregnated paper used to detect liquid substances for the presence of V- and G-type nerve agents and H- and L-type blister agents.

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Hill KK, Smith TJ (2013). "Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes". In Rummel A, Binz T (eds.).

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allows the spores to germinate, after which the bacteria can multiply and produce toxin. Critically, ingestion of toxin rather than spores or vegetative bacteria causes

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was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and provided it to the academic community.

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The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain

1244:. As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell 6871: 6655:

Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM (December 2000). "Botulinum toxin type A (Botox) for treatment of migraine headaches: an open-label study".

4647:"Revance Announces FDA Approval of Daxxify (DaxibotulinumtoxinA-lanm) for Injection, the First and Only Peptide-Formulated Neuromodulator With Long-Lasting Results" 11105: 7279: 3984:

Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D (December 2011). Duthie JB (ed.). "Botulinum toxin injections for adults with overactive bladder syndrome".

849:. The toxin is also used commercially for medical and cosmetic purposes. Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent. 8266: 1307:

acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.

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Jackson JL, Kuriyama A, Hayashino Y (April 2012). "Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis".

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and confirmed that a toxin produced by the bacteria causes botulism. On 14 December 1895, there was a large outbreak of botulism in the Belgian village of

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Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and

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Over the next three decades, 1895–1925, as food canning was approaching a billion-dollar-a-year industry, botulism was becoming a public health hazard.

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to a 50-kDa light chain polypeptide. The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to

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Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to presynaptic surface of

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horizontal lines on the forehead, crow's feet around the eyes, and even circular bands that form around the neck secondary to platysmal hyperactivity.

595: 8489: 6931: 11120: 4567: 1157:(an anaerobic, gram-positive bacterium) is the cause of botulism. Humans most commonly ingest the toxin from eating improperly canned foods in which 5934:

Erbguth FJ (March 2004). "Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin".

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As of 2018, botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the

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Giesler M (2012). "How Doppelgänger Brand Images Influence the Market Creation Process: Longitudinal Insights from the Rise of Botox Cosmetic".

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Magid M, Keeling BH, Reichenberg JS (November 2015). "Neurotoxins: Expanding Uses of Neuromodulators in Medicine--Major Depressive Disorder".

2180:, intellectual disability, and cerebral palsy. Injection of botulinum toxin type-A into salivary glands is useful in reducing the secretions. 11770: 11347: 11213: 4336: 782: 109: 8540: 8082:

Keen M, Kopelman JE, Aviv JE, Binder W, Brin M, Blitzer A (April 1994). "Botulinum toxin A: a novel method to remove periorbital wrinkles".

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Finzi E, Rosenthal NE (May 2014). "Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial".

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available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of

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Erbguth FJ, Naumann M (November 1999). "Historical aspects of botulinum toxin: Justinus Kerner (1786-1862) and the "sausage poison"".

2412: 14487: 11830: 11318: 10591: 7390: 4939:"Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases" 4141: 5419: 3418: 1881:

Botulinum toxin A is sold under the brand names Jeuveau, Botox, and Xeomin. Botulinum toxin B is sold under the brand name Myobloc.

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in December 2000. Brand names for botulinum toxin type-B include Myobloc in the United States and Neurobloc in the European Union.

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Besides the three primary US manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Germany by

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In 2020, 4,401,536 botulinum toxin Type A procedures were administered. In 2019 the botulinum toxin market made US$ 3.19 billion.

1050:, especially in the uppermost third of the face. Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from 775: 11785: 11660: 7001: 6390: 5129: 2744: 2714: 2232: 5530:

Barash JR, Arnon SS (January 2014). "A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins".

5478: 3690: 2933: 2894: 2864: 2799: 2774: 2684: 2297: 9674: 3184:

Rosales RL, Bigalke H, Dressler D (February 2006). "Pharmacology of botulinum toxin: differences between type A preparations".

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Figgitt DP, Noble S (2002). "Botulinum toxin B: a review of its therapeutic potential in the management of cervical dystonia".

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dystonia in adults, severe axillary hyperhidrosis (or other areas of the body), blepharospasm, upper or lower limb spasticity.

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Wellman-Labadie O, Zhou Y (May 2010). "The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?".

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Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label.

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Mazzuco R, Hexsel D (December 2010). "Gummy smile and botulinum toxin: a new approach based on the gingival exposure area".

5411: 2332: 2117:. Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the 9102: 6138:

Lamanna C, McELROY OE, Eklund HW (May 1946). "The purification and crystallization of Clostridium botulinum type A toxin".

5500: 5211: 1714: 602: 207: 6893: 3643:"Efficacy and Safety of Botulinum Toxin Type A in Spasticity Caused by Spinal Cord Injury: A Randomized, Controlled Trial" 2450: 1784:) will increase mortality by enhancing botulinum toxin's mechanism of toxicity. With regard to detection, protocols using 1184:

Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (serotypes A, B, E) botulinum

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Clark RP, Berris CE (August 1989). "Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis".

5441: 8256: 7024: 1303:. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the 14482: 12551: 11355: 7593: 6343:

Scott AB (October 1980). "Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery".

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and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein

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Magoon E, Cruciger M, Scott AB, Jampolsky A (May 1982). "Diagnostic injection of Xylocaine into extraocular muscles".

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Janes LE, Connor LM, Moradi A, Alghoul M (April 2021). "Current Use of Cosmetic Toxins to Improve Facial Aesthetics".

14169: 9930: 9922: 7249: 2192:, but it can become ineffective after a time. Botulinum toxin type B received FDA approval for treatment of cervical 2026: 1864: 1531: 977: 11635: 9926: 9814: 9666: 9224: 1509: 10029: 9900: 9087: 7339: 1237: 1017: 720: 297: 188: 7959:"Botulinum toxin therapy of eye muscle disorders. Safety and effectiveness. American Academy of Ophthalmology". 7186:

McAdams D, Kornblet S (2011). "Baader-Meinhof Group (OR Baader-Meinhof Gang". In Pilch RF, Zilinskas RA (eds.).

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Carruthers JD, Carruthers JA (January 1992). "Treatment of glabellar frown lines with C. botulinum-A exotoxin".

5176: 13760: 11174: 10719: 10676: 9012: 6953: 5249: 4966: 4727: 4432: 2205: 1513: 1193: 702: 6112: 1170: 1046:

In cosmetic applications, botulinum toxin is considered relatively safe and effective for reduction of facial

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Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including

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for "An Exploratory Study of the Safety and Efficacy of Botox for the Treatment of Premature Ejaculation" at

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issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.

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Pellett S (June 2012). "Learning from the past: historical aspects of bacterial toxins as pharmaceuticals".

14121: 13731: 12698: 12437: 11051: 9052: 9042: 8497: 8493: 8129: 7760: 7343: 7313: 7253: 7223: 6964: 6432: 5375: 5342: 5305: 5275: 5245: 5172: 4733: 4689: 4608: 4145: 2099: 1806:, which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found. 973: 520: 455: 7729: 6923: 4559: 2102:(FDA) approved an alternative product-safety testing method in response to increasing public concern that 787: 11645: 2384:"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)" 2264: 2014: 1030:. However, the use of botulinum toxin injections for episodic migraine has not been approved by the FDA. 695: 255: 2614: 2588: 969:

for treatment of restricted ankle motion due to lower-limb spasticity associated with stroke in adults.

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Carruthers JD, Fagien S, Joseph JH, Humphrey SD, Biesman BS, Gallagher CJ, et al. (January 2020).

8234: 6265:

Drachman DB (August 1964). "Atrophy of Skeletal Muscle in Chick Embryos Treated with Botulinum Toxin".

2707:"Alluzience, 200 Speywood units/ml, solution for injection - Summary of Product Characteristics (SmPC)" 2242: 2065:

In December 1989, Botox was approved by the US FDA for the treatment of strabismus, blepharospasm, and

2017:

and thus deactivated at temperatures greater than 85 °C (185 °F) for five minutes. As a zinc

8450:"Botulinum toxin A for treatment of sialorrhea in children: an effective, minimally invasive approach" 4181:

Pavone V, Testa G, Restivo DA, Cannavò L, Condorelli G, Portinaro NM, et al. (19 February 2016).

3230: 1987: 14512: 14492: 14426: 14413: 14400: 14387: 14374: 14361: 14348: 14310: 13736: 13456: 13149: 13118: 11079: 9531: 9005: 6316:

Scott AB, Rosenbaum A, Collins CC (December 1973). "Pharmacologic weakening of extraocular muscles".

2383: 13353: 11013: 8339:"Surface anatomy of the lip elevator muscles for the treatment of gummy smile using botulinum toxin" 8208: 4761:

Mittal SO, Safarpour D, Jabbari B (February 2016). "Botulinum Toxin Treatment of Neuropathic Pain".

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Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,

723: 14532: 14527: 14320: 14274: 14217: 14131: 13948: 13791: 13218: 13154: 12525: 12178: 12075: 11800: 10230: 2126: 2118: 1943: 1932: 1846: 1038: 647: 625: 7466: 4328: 3362:"Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy" 14497: 14222: 13681: 13536: 13441: 13223: 12997: 12819: 12734: 10014: 10002: 9806: 9795: 8530: 8039:

Koudsie S, Coste-Verdier V, Paya C, Chan H, Andrebe C, Pechmeja J, et al. (April 2021). "".

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Carruthers A (November–December 2003). "History of the clinical use of botulinum toxin A and B".

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Rohrich RJ, Janis JE, Fagien S, Stuzin JM (October 2003). "The cosmetic use of botulinum toxin".

1954: 1617: 1502: 1063: 244: 80: 17: 9259: 7617:"Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic?" 6954:"BOTOX (onabotulinumtoxinA) for injection, for intramuscular, intradetrusor, or intradermal use" 5827:"Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics" 1395:

One of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in the village of

163: 13752: 13496: 13406: 13396: 13333: 12814: 10048: 9986: 9744: 9238: 9199: 9194: 9149: 2767:"Xeomin 50 units powder for solution for injection - Summary of Product Characteristics (SmPC)" 2737:"Letybo 50 units powder for solution for injection - Summary of Product Characteristics (SmPC)" 924:. Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the 838: 155: 13368: 10062: 9281: 8825:"Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A" 7992:"Botulinum toxin in the management of blepharospasm: current evidence and recent developments" 1616:. Allergan then began using the trademark Botox. This original approval was granted under the 14243: 14162: 14106: 13706: 13348: 13159: 13007: 12443: 12364: 10837: 10472: 9833: 9625: 9456: 9209: 9092: 7500: 5568:

Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, et al. (October 2005).

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gang safe house in Paris and had found a makeshift laboratory that contained flasks full of

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symptoms. In addition to these uses, botulinum toxin is being evaluated for use in treating

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During the early 1980s, German and French newspapers reported that the police had raided a

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Syed YY (August 2017). "AbobotulinumtoxinA: A Review in Pediatric Lower Limb Spasticity".

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Proper refrigeration at temperatures below 4.4 °C (39.9 °F) slows the growth of

1986: with: modern content and referencing on antibiotic susceptibilities. You can help by 1403:, Germany. Thirteen people became sick and six died after eating pork stomach filled with 1400: 659: 147: 123: 8: 14279: 13591: 13576: 13343: 13313: 13293: 13029: 12977: 12916: 12454: 12354: 12283: 12100: 12050: 11575: 11002: 9184: 9174: 9144: 9129: 9082: 8926: 8448:

Khan WU, Campisi P, Nadarajah S, Shakur YA, Khan N, Semenuk D, et al. (April 2011).

8261: 7877:"Investigations into small molecule non-peptidic inhibitors of the botulinum neurotoxins" 5785:. Current Topics in Microbiology and Immunology. Vol. 364. Springer. pp. 1–20. 5242:"FDA Gives Update on Botulinum Toxin Safety Warnings; Established Names of Drugs Changed" 5212:"FDA Gives Update on Botulinum Toxin Safety Warnings; Established Names of Drugs Changed" 2073: 1926: 1838: 1346: 986: 630: 381: 7892: 7126: 6278: 6151: 3477:"Crystal structure of the catalytic domain of the Weissella oryzae botulinum-like toxin" 2502: 2076:

in people younger than 12 years of age, several studies have yielded differing results.

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Please help update this article to reflect recent events or newly available information.

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With the outbreak of World War II, weaponization of botulinum toxin was investigated at

985:. Botulinum toxins have been used off-label for several pediatric conditions, including 524: 14507: 14212: 13164: 12987: 12921: 12839: 12727: 12171: 11875: 11054: 10940: 10110: 10068: 9945: 9776: 9397: 9164: 9159: 9154: 8851: 8806: 8762: 8674: 8631: 8588: 8314: 8289: 8182: 8107: 8064: 8016: 7991: 7909: 7876: 7694: 7667: 7643: 7616: 7439: 7422: 6759: 6734: 6680: 6633: 6595: 6560: 6522: 6395: 6368: 6298: 6207: 6182: 6054: 6029: 6005: 5959: 5904: 5853: 5758: 5698: 5673: 5651: 5594: 5569: 5104: 5087: 5063: 5038: 5014: 4989: 4907: 4880: 4786: 4496: 4469: 4301: 4276: 4257: 4209: 3961: 3936: 3876: 3825: 3800: 3781: 3667: 3642: 3618: 3593: 3534: 3517: 3386: 3361: 3330: 3209: 3130: 3084: 3036: 2138: 1589: 1585: 1225: 948: 858: 218: 7968: 7817: 7792: 7551: 7526: 6993: 6356: 6243: 5470: 2976:

Montecucco C, Molgó J (June 2005). "Botulinal neurotoxins: revival of an old killer".

2736: 2706: 2443:"Nuceiva prabotulinumtoxinA 100 Units Powder for Solution for Injection vial (381094)" 2210:

Onabotulinumtoxin A (trade name Botox) received FDA approval for treatment of chronic

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serotypes cause human botulism, with the activities of types A and B enduring longest

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in 2009, warning that botulinum toxin products can spread to other parts of the body.

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note: some toxins are produced by lower species and pass through intermediate species

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Solish N, Carruthers J, Kaufman J, Rubio RG, Gross TM, Gallagher CJ (December 2021).

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Shukla HD, Sharma SK (2005). "Clostridium botulinum: a bug with beauty and weapon".

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Botulism can be difficult to diagnose, as it may appear similar to diseases such as

14258: 14253: 14227: 14155: 13511: 13476: 13072: 12962: 12941: 12834: 12764: 12657: 12638: 12334: 12135: 12130: 12125: 12120: 12115: 12110: 12105: 11910: 11790: 11780: 11610: 11068: 10884: 10702: 10308: 10224: 10166: 9972: 9596: 8846: 8836: 8801: 8791: 8730: 8658: 8615: 8592: 8572: 8461: 8422: 8387: 8350: 8309: 8301: 8174: 8091: 8048: 8011: 8003: 7964: 7904: 7896: 7849: 7812: 7804: 7689: 7679: 7638: 7628: 7546: 7538: 7527:"Properties and use of botulinum toxin and other microbial neurotoxins in medicine" 7434: 7191: 6754: 6746: 6707: 6664: 6629: 6591: 6556: 6518: 6480: 6352: 6282: 6239: 6202: 6198: 6194: 6155: 6086: 6049: 6041: 5989: 5963: 5943: 5899: 5889: 5848: 5838: 5786: 5753: 5743: 5693: 5685: 5633: 5589: 5581: 5539: 5099: 5058: 5050: 5009: 5001: 4950: 4902: 4892: 4854: 4850: 4817: 4770: 4491: 4481: 4374: 4296: 4288: 4241: 4204: 4194: 4024: 3993: 3989: 3956: 3948: 3909: 3871: 3861: 3820: 3812: 3729: 3662: 3654: 3613: 3605: 3566: 3529: 3488: 3381: 3377: 3373: 3325: 3315: 3193: 3164: 3114: 3088: 3068: 3020: 2985: 2066: 1375: 1327: 1304: 1124: 1088: 827: 537: 280: 8997: 8757: 8695: 7900: 7808: 7666:

Hill KK, Xie G, Foley BT, Smith TJ, Munk AC, Bruce D, et al. (October 2009).

4822: 4805: 4028: 2473:"Prescription medicines: registration of new chemical entities in Australia, 2014" 2357: 1949:

Food-borne botulism results, indirectly, from ingestion of food contaminated with

33: 14466: 14305: 14289: 14202: 13811: 13651: 13531: 13426: 13411: 13358: 13133: 13123: 12859: 12824: 12475: 12470: 12278: 11565: 11555: 11535: 10967: 10872: 10467: 10122: 10019: 9864: 9724: 9652: 9465: 9451: 9415: 9029: 8796: 8779: 8662: 7542: 6286: 6159: 4292: 4098: 3913: 3734: 3717: 3118: 2830:"Botox Cosmetic- onabotulinumtoxina injection, powder, lyophilized, for solution" 2328: 2177: 2018: 1412: 1292: 1261: 937: 873: 8126:"Botulinum Toxin Type A Product Approval Information – Licensing Action 4/12/02" 7220:"Botulinum Toxin Type A Product Approval Information - Licensing Action 4/12/02" 5790: 4112:"UK's MHRA approves Botox for treatment of ankle disability in stroke survivors" 1248:. Botulinum neurotoxins recognize distinct classes of receptors simultaneously ( 742: 14454: 14343: 14284: 13601: 13516: 13466: 13461: 13288: 13184: 13128: 12911: 11885: 11805: 11560: 11530: 11370: 10909: 10457: 10397: 10220: 10212: 9959: 9913: 9682: 9344: 8841: 8824: 8426: 8337:

Hwang WS, Hur MS, Hu KS, Song WC, Koh KS, Baik HS, et al. (January 2009).

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Singh JA, Fitzgerald PM (September 2010). "Botulinum toxin for shoulder pain".

4356: 4354: 3169: 3152: 3151:

Al-Ghamdi AS, Alghanemy N, Joharji H, Al-Qahtani D, Alghamdi H (January 2015).

2989: 2442: 2298:"Letybo- letibotulinumtoxina-wlbg injection, powder, lyophilized, for solution" 2142: 1797: 1581: 1561: 1300: 1284: 1100: 901: 758: 46: 13561: 12193: 8619: 8391: 8052: 7853: 6090: 5748: 5731: 4245: 4015:

Scott AB (1994). "Change of eye muscle sarcomeres according to eye position".

3320: 3303: 3231:"Botulism toxin X: Time to update the textbooks, thanks to genomic sequencing" 3072: 2934:"Daxxify- botulinum toxin type a injection, powder, lyophilized, for solution" 2895:"Dysport- botulinum toxin type a injection, powder, lyophilized, for solution" 1408: 1387: 14476: 14248: 14207: 13661: 13656: 13631: 13556: 13471: 13248: 12967: 12809: 12263: 12095: 11870: 11835: 11710: 11365: 11044: 10899: 10842: 10596: 10559: 10507: 10452: 10437: 10313: 10273: 10216: 10010: 9859: 9782: 9561: 9551: 9506: 9501: 9496: 9367: 9324: 9309: 9290: 9249: 8516: 8466: 8449: 8152: 8007: 7840:

Setlow P (April 2007). "I will survive: DNA protection in bacterial spores".

7366: 7280:"Hugel's 'Letybo' First in Korea to Obtain Marketing Approval from Australia" 7034: 6458: 5878:"Identification of a novel botulinum neurotoxin gene cluster in Enterococcus" 5398: 5195: 5142: 4714: 4633: 4199: 4182: 4168: 3816: 3408: 2649: 2137:

Botulinum toxin type-A is now a common treatment for muscles affected by the

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would be only used to describe a group of anaerobic microorganisms. In 1919,

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Farag SM, Mohammed MO, El-Sobky TA, ElKadery NA, ElZohiery AK (March 2020).

65: 14197: 13581: 13566: 13506: 13416: 13378: 13077: 12972: 12619: 12410: 12303: 12258: 12223: 12213: 12208: 12055: 11935: 11840: 11745: 11570: 11380: 11263: 11248: 10962: 10952: 10935: 10904: 10852: 10816: 10775: 10729: 10666: 10569: 10492: 10427: 10262: 10258: 10254: 10240: 10054: 9890: 9687: 9611: 9470: 9441: 9304: 9299: 9033: 8860: 8815: 8742: 8670: 8627: 8584: 8475: 8434: 8399: 8364: 8323: 8095: 8060: 8025: 7918: 7861: 7703: 7684: 7652: 7633: 7448: 7310:"Drug Approval Package: Xeomin (incobotulinumtoxinA) Injection NDA #125360" 6768: 6719: 6676: 6603: 6568: 6492: 6294: 6216: 6167: 6098: 6063: 6001: 5955: 5913: 5862: 5843: 5826: 5808: 5767: 5707: 5647: 5603: 5585: 5551: 5113: 5072: 5054: 5023: 5005: 4962: 4916: 4862: 4831: 4782: 4774: 4541: 4505: 4388: 4310: 4253: 4218: 4183:"Botulinum Toxin Treatment for Limb Spasticity in Childhood Cerebral Palsy" 4001: 3970: 3921: 3885: 3834: 3777: 3743: 3676: 3627: 3578: 3543: 3502: 3395: 3339: 3205: 3126: 3080: 3032: 2997: 1785: 1773: 1557: 1363: 1204: 1096: 1062:, Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by 1014: 941: 275: 8103: 7976: 7945: 7826: 7560: 6711: 6641: 6530: 6364: 6329: 6251: 5993: 5730:

Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL (December 2010).

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Stavropoulos SN, Friedel D, Modayil R, Iqbal S, Grendell JH (March 2013).

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Ashkenazi A (March 2010). "Botulinum toxin type a for chronic migraine".

8355: 8338: 6045: 5570:"Botulinum neurotoxin detection and differentiation by mass spectrometry" 4806:"Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses" 4486: 3952: 3609: 3411:"OnabotulinumtoxinA (Botulinum Toxin Type A) Monograph for Professionals" 2030: 2021:(see below), the toxin's activity is also susceptible, post-exposure, to 1899: 1781: 1420:

to describe the disease caused by sausage poisoning, from the Latin word

1351: 1280: 1249: 1241: 1233: 921: 671: 174: 55: 12188: 6832:"2020 National Plastic Surgery Statistics: Cosmetic Surgical Procedures" 4528:

Small R (August 2014). "Botulinum toxin injection for facial wrinkles".

3658: 2800:"Botox- onabotulinumtoxina injection, powder, lyophilized, for solution" 1974: 945: 428: 420: 14101: 13973: 13626: 13621: 13541: 13491: 13486: 13421: 13278: 13108: 13049: 12936: 12789: 12672: 12668: 12400: 12390: 12385: 12298: 12273: 12233: 12228: 12218: 12203: 12144: 12139: 11950: 11810: 11795: 11765: 11740: 11715: 11670: 11665: 11655: 11625: 11595: 11459: 11449: 11394: 11389: 11360: 11337: 11303: 11268: 11253: 11218: 11193: 11047: 10957: 10894: 10811: 10789: 10734: 10697: 10641: 10611: 10601: 10542: 10532: 10517: 10502: 10497: 10482: 10402: 10387: 10303: 10293: 10288: 10278: 10245: 9935: 9895: 9712: 9707: 9633: 9601: 9571: 9556: 9546: 9526: 9387: 9377: 9362: 9352: 8178: 2173: 2158: 1946:

across lineages, contributing to the multi-species pattern seen today.

1577: 1516: in this section. Unsourced material may be challenged and removed. 1438: 1189: 959: 917: 905: 811: 576: 439: 98: 41: 13431: 6783:"New plastic surgery statistics reveal trends toward body enhancement" 6750: 6735:"Therapeutic use of botulinum toxin in migraine: mechanisms of action" 5947: 5638: 5621: 5088:"Minimizing bruising following fillers and other cosmetic injectables" 3764:

Felber ES (October 2006). "Botulinum toxin in primary care medicine".

14395: 14369: 13641: 13586: 13318: 12931: 12895: 12890: 12885: 12784: 12750: 12511: 12395: 12344: 12253: 12248: 12238: 12080: 12015: 12010: 12000: 11955: 11925: 11920: 11905: 11890: 11860: 11825: 11815: 11720: 11600: 11590: 11580: 11550: 11545: 11540: 11464: 11439: 11404: 11333: 11308: 11278: 11238: 11188: 11043: 10862: 10857: 10847: 10827: 10770: 10760: 10755: 10714: 10626: 10442: 10422: 10412: 10372: 10367: 10347: 10318: 10268: 10250: 10203: 10195: 10102: 10086: 9697: 9511: 9382: 9372: 9329: 7791:

Licciardello JJ, Nickerson JT, Ribich CA, Goldblith SA (March 1967).

4379: 4363:"Hyperhidrosis: evolving therapies for a well-established phenomenon" 4362: 1645: 1447: 1245: 1185: 1116: 925: 113: 7790: 7250:"Drug Approval Package: Dysport (abobotulinumtoxin) NDA #125274s000" 4938: 4937:

Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM (September 2005).

1772:

Botulinum toxin has been recognized as a potential agent for use in

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Canadian Journal of Ophthalmology. Journal Canadien d'Ophtalmologie

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AbobotulinumtoxinA has been approved for the treatment of axillary

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