Does Botulinum toxin cause botulism?
Botulism
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium "Clostridium botulinum". The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.
Botulism can be spread in several ways. The bacterial spores which cause it are common in both soil and water. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism happens when the bacteria develops in the intestines and releases the toxin. This typically only occurs in children less than six months old, as protective mechanisms develop after that time. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. It is not passed directly between people. The diagnosis is confirmed by finding the toxin or bacteria in the person in question.
Prevention is primarily by proper food preparation. The toxin, though not the organism, is destroyed by heating it to more than for longer than 5 minutes. Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin, "botulus", meaning sausage. Early descriptions of botulism date from at least as far back as 1793 in Germany.
Technological and industrial history of 21st-century Canada
In 2002, two Vancouver doctors, dermatologist Alastair Carruthers and ophthalmologist Jean Carruthers, pioneered the cosmetic use of the well known botulinum toxin. The pair noticed that subcutaneous injections of small amounts of the toxin had the effect of removing age wrinkles from the skin. The Botox procedure, as it became known, quickly gained popularity around the world.
Botulinum toxin
In 1895 (seventy-five years later), Émile van Ermengem, professor of bacteriology and a student of Robert Koch, correctly described "Clostridium botulinum" as the bacterial source of the toxin. Thirty-four attendees at a funeral were poisoned by eating partially salted ham, an extract of which was found to cause botulism-like paralysis in laboratory animals. Van Ermengem isolated and grew the bacterium, and described its toxin, which was later purified by P Tessmer Snipe and Hermann Sommer.
Botulinum toxin
Botulinum toxin A is marketed under the brand names Botox and Xeomin. Botulinum toxin B is marketed under the brand name Myobloc.
Clostridium botulinum
Adult intestinal toxemia:
A very rare form of botulism that occurs by the same route as infant botulism but is among adults. Occurs rarely and sporadically. Signs and symptoms include:
Botulism
From 1985-2015 there was an outbreak of 91 confirmed cases of foodborne botulism in Canada, 85% of which were in Inuit communities, especially Nunavik and First Nations of the coast of British Columbia from eating traditionally prepared marine mammal and fish products.
Botulism
The spores require warm temperatures, a protein source, an anaerobic environment, and moisture in order to become active and produce toxin. In the wild, decomposing vegetation and invertebrates combined with warm temperatures can provide ideal conditions for the botulism bacteria to activate and produce toxin that may affect feeding birds and other animals. Spores are not killed by boiling, but botulism is uncommon because special, rarely obtained conditions are necessary for botulinum toxin production from C. botulinum spores, including an anaerobic, low-salt, low-acid, low-sugar environment at ambient temperatures.
Botulinum toxin
Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium "Clostridium botulinum" and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.
Botulinum toxin
In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A U.S. supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications 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 manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the U.S. and other countries.
Management of strabismus
Botulinum toxin is a neurotoxin present in the cytoplasm of the anaerobic bacterium "Clostridium botulinum". It binds presynaptically with high affinity to sites on cholinergic nerve terminals, decreasing release of acetylcholine, thereby blocking neuromuscular transmission, and causing flaccid muscle paralysis. Crotoxin appears to act similarly.
Botulism
Toxin is produced by the bacteria when environmental conditions are favourable for the spores to replicate and grow, but the gene that encodes for the toxin protein is actually carried by a virus or phage that infects the bacteria. Unfortunately, little is known about the natural factors that control phage infection and replication within the bacteria.
Clostridium botulinum
Botulinum toxin produced by "C. botulinum" is often believed to be a potential bioweapon as it is so potent that it takes about 75 nanograms to kill a person ( of 1 ng/kg, assuming an average person weighs ~75 kg); 1 kilogram of it would be enough to kill the entire human population. For comparative purposes, a quarter of a typical grain of sand's weight (350 ng) of botulinum toxin would constitute a lethal dose for humans.
Tinnitus
Botulinum toxin injection has been tried with some success in some of the rare cases of objective tinnitus from a palatal tremor.
Temporomandibular joint dysfunction
Botulinum toxin solution ("Botox") is sometimes used to treat TMD. Injection of botox into the lateral pterygoid muscle has been investigated in multiple randomized control trials, and there is evidence that it is of benefit in TMD. It is theorized that spasm of lateral pterygoid causes anterior disc displacement. Botulinum toxin causes temporary muscular paralysis by inhibiting acetylcholine release at the neuromuscular junction. The effects usually last for a period of months before they wear off. Complications include the creation of a "fixed" expression due to diffusion of the solution and subsequent involvement of the muscles of facial expression, which lasts until the effects of the botox wear off. Injections of local anesthetic, sometimes combined with steroids, into the muscles (e.g. the temoralis muscle or its tendon) are also sometimes used. Local anesthetics may provide temporary pain relief, and steroids inhibit pro-inflammatory cytokines. Steroids and other medications are sometimes injected directly into the joint (See Intra-articular injections).
Botulinum toxin
Botulinum toxin has been recognized as a potential agent for use in bioterrorism. It can be absorbed through the eyes, mucous membranes, respiratory tract, or non-intact skin.
Clostridium botulinum
Only botulinum toxin types A, B, E, F and H cause disease in humans. Types A, B, and E are associated with food-borne illness, with type E specifically associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals. No disease is associated with type G. The "gold standard" for determining toxin type is a mouse bioassay, but the genes for types A, B, E, and F can now be readily differentiated using quantitative PCR. As no antitoxin to type H is yet available, discovered in 2013 and by far the deadliest, details are kept under shroud.
Clostridium botulinum
Neurotoxin production is the unifying feature of the species. Eight types of toxins have been identified that are allocated a letter (A–H), several of which can cause disease in humans. They are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxin to be absorbed from the intestines into the bloodstream.
However, all types of botulinum toxin are rapidly destroyed by heating to 100 °C for 15 minutes (900 seconds).
Jean-Baptiste Botul
Jean-Baptiste Botul is a fictional French philosopher created in 1995 by the journalist Frédéric Pagès and other members of a group calling itself the Association of the Friends of Jean-Baptiste Botul. Originating as a literary hoax, the names of both Botul and his philosophy of "botulism" derive from botulism, an illness caused by the bacterium "Clostridium botulinum". References to Botul were first made in publications by members of the association and later turned up in texts by writers who were not party to the hoax and thought Botul was a real person, notably the French philosopher Bernard-Henri Lévy. There is now an annual Botul Prize awarded for a book that mentions Botul.
Management of strabismus
Botulinum toxin injection is commonly used for small and moderate degrees of infantile "esotropia", acquired adult strabismus, and where it is a consequence of retinal detachment surgery, that is, in cases where there is good potential for binocular vision, so that the corrected alignment can be stabilized by motor fusion. "Sixth nerve palsy," paralysis of the "lateral rectus", the muscle that rotates the eye outwards, is most frequently caused by an ischemic event, from which there is frequently substantial recovery. But during the acute stage of paresis, the lateral rectus is stretched and grows longer, and its antagonist medial rectus shortens. Sixth nerve palsy is treated by injecting the medial rectus muscle, thereby allowing the lateral rectus, paretic though it be, to stretch and lengthen the medial, while it shortens, so that, when the sixth nerve paresis subsides, alignment is improved. The toxin is also useful in other cranial nerve palsies affecting eye muscles. Residual misalignments that remain following traditional strabismus surgery can be corrected with toxin injection. Toxin injections are used for temporary relief during the acute phase of thyroid ophthalmopathy, when misalignments are too unstable to treat surgically. Botulinum toxin has also been used intraoperatively to augment a surgical effect. In complex strabismus cases, toxin can be injected diagnostically as an aid to planning surgical treatment.
Botulism
Botulism can result in death due to respiratory failure. However, in the past 50 years, the proportion of patients with botulism who die has fallen from about 50% to 7% due to improved supportive care. A patient with severe botulism may require mechanical ventilation (breathing support through a ventilator) as well as intensive medical and nursing care, sometimes for several months. The person may require rehabilitation therapy after leaving the hospital.
Wrinkle
Botulinum toxin is a neurotoxin protein produced by the bacterium "Clostridium botulinum". Botox is a specific form of botulinum toxin manufactured by Allergan for both therapeutic and cosmetic use. Besides its cosmetic application, Botox is used in the treatment of other conditions including migraine headache and cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck).
Migraine treatment
OnabotulinumtoxinA (trade name Botox) received FDA approval for treatment of chronic migraines (occurring more than 15 days per month) in 2010. The toxin is injected into the muscles of head and neck. Approval followed evidence presented to the agency from two studies funded by Allergan, Inc. showing a very slight improvement in incidence of chronic migraines for migraine sufferers undergoing the Botox treatment. Since then, several randomized control trials have shown Botulinum Toxin Type A to improve headache symptoms and quality of life when used prophylactically for patients with chronic migraine
Clostridium botulinum
The control of food-borne botulism caused by "C. botulinum" is based almost entirely on thermal destruction (heating) of the spores or inhibiting spore germination into bacteria and allowing cells to grow and produce toxins in foods. Conditions conducive of growth are dependent on various environmental factors.
Growth of "C. botulinum" is a risk in low acid foods as defined by having a pH greater than 4.6 although growth is significantly retarded for pH below 4.9. There have been some cases and specific conditions reported to sustain growth with pH below 4.6.
Botulinum toxin therapy of strabismus
Botulinum toxin is the most acutely lethal toxin that is known. It is produced by the bacterium clostridium botulinum. It acts inside nerve terminals by decreasing the release of acetylcholine, blocking neuromuscular transmission and thereby causing flaccid muscular paralysis. As a result, the muscle is weakened for about 3 to 4 months.
Botulinum toxin therapy of strabismus
Some consider botulinum injections to be a treatment option for children with small- to moderate-angle infantile esotropia. Studies have provided indications that performing injections into both medial rectus muscles may be more effective than an injection into one medial rectus muscle alone.
Wrinkle
Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles. It is not appropriate for the treatment of all wrinkles; it is indicated for the treatment of glabellar lines (between the eyebrows) in adults. Any other usage is not approved by the FDA and is considered off-label use.
Neurotoxin
Neurotoxins are toxins that are poisonous or destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), manganese glutamate, nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin, and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.
Notalgia paresthetica
Most recently intradermal injections of botulinum toxin type A (Botox) have been tried with some success. Even though botulinum normally wears off in three to six months, the treatment appears to be long term, and it has been theorised that botulinum type A effects lasting change in pain signaling. Unfortunately, repeated injections have been associated with diminished movement ability of the upper back and arms and its recommendation as a treatment has therefore become less popular.
Botulinum toxin
In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache.
Botulism
The toxin is the protein botulinum toxin produced under anaerobic conditions (where there is no oxygen) by the bacterium "Clostridium botulinum".
Botulinum toxin
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 can include arrhythmia, heart attack, and in some cases seizures, respiratory arrest, and death. Additionally, side effects which are common in cosmetic use are also common in therapeutic use, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes.
Synaptobrevin
Synaptobrevin is degraded by tetanospasmin, a protein derived from the bacterium "Clostridium tetani", which causes tetanus. A related bacterium, "Clostridium botulinum", produces the botulinum toxin. Various botulinum toxin serotypes exist that each cleave specific peptide bonds of specific neuronal SNARE proteins, and synaptobrevin is this target protein for several of the serotypes.
Home canning
While it is possible to safely preserve many kinds of foodstuffs, home canning can expose consumers to botulism and other kinds of food poisoning if done incorrectly. The most common source of food-borne botulism is home-canned foods prepared in an unsafe manner. Safety measures must be taken when performing home canning, since ingestion of toxin in food produced by "Clostridium botulinum" can cause death. Because of the high risk of illness or death associated with improper canning techniques, the United States Department of Agriculture (USDA) considers it critical that consumers who intend to can at home obtain proper and current information from a reliable source. At the basis of these recommendations is the balance between bringing the food to a high enough temperature for a long enough time that spoilage and disease-producing microorganisms are killed, while not heating the food so much that it loses nutritive value or palatability.
SNARE (protein)
In each of these cases, Botulinum Neurotoxin causes functional damage to SNARE proteins, which has significant physiological and medical implications. By damaging SNARE proteins, the toxin prevents synaptic vesicles from fusing to the synaptic membrane and releasing their neurotransmitters into the synaptic cleft. With the inhibition of neurotransmitter release into the synaptic cleft, action potentials cannot be propagated to stimulate muscle cells. This result in paralysis of those infected and in serious cases, it can cause death. Although the effects of Botulinum Neurotoxin can be fatal, it has also been used as a therapeutic agent in medical and cosmetic treatments.
Fish sauce
In 2014, the US Food and Drug Administration (FDA) banned the import of Thai fish sauces due to lack of information about tests for botulinum toxin. The toxin can cause death if more than 0.5 microgram is consumed. The Thai Office of Food Safety and Quality then tested 48 brands of fish sauce to determine the content of botulinum toxin in the products. Of 48 brands tested, 28 were genuine fish sauce from 18 production sites in 12 provinces. Twenty samples from production sites in eight provinces were adulterated fish sauce. Tests showed that none were contaminated with botulinum toxin types A, B, E and F and were free of clostridium botulinum bacteria. In 2018, rumours again surfaced concerning banned Thai fish sauce.
Botulism
The growth of the spores releases botulinum toxin, which is then absorbed into the bloodstream and taken throughout the body, causing paralysis by blocking the release of acetylcholine at the neuromuscular junction. Typical symptoms of infant botulism include constipation, lethargy, weakness, difficulty feeding and an altered cry, often progressing to a complete descending flaccid paralysis. Although constipation is usually the first symptom of infant botulism, it is commonly overlooked.
Botulism
Severe botulism leads to reduced movement of the muscles of respiration, and hence problems with gas exchange. This may be experienced as dyspnea (difficulty breathing), but when severe can lead to respiratory failure, due to the buildup of unexhaled carbon dioxide and its resultant depressant effect on the brain. This may lead to respiratory compromise and death if untreated.
Botulism
Oils infused with fresh garlic or herbs should be acidified and refrigerated. Potatoes which have been baked while wrapped in aluminum foil should be kept hot until served or refrigerated. Because the botulism toxin is destroyed by high temperatures, home-canned foods are best boiled for 10 minutes before eating. Metal cans containing food in which bacteria, possibly botulinum, are growing may bulge outwards due to gas production from bacterial growth; such cans should be discarded.
Management of strabismus
Botulinum A toxin (introduced as Oculinum), now called Botox, is the principal drug used to temporarily paralyze extraocular muscles, and is widely accepted as an alternative to surgery for many types of strabismus. "Crotoxin", a snake neurotoxin, is being developed in Belo Horizonte, Brazil as a potential alternative.
Botulism
The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nerves—a group of twelve nerves that control eye movements, the facial muscles and the muscles controlling chewing and swallowing. Double vision, drooping of both eyelids, loss of facial expression and swallowing problems may therefore occur. In addition to affecting the voluntary muscles, it can also cause disruptions in the autonomic nervous system. This is experienced as a dry mouth and throat (due to decreased production of saliva), postural hypotension (decreased blood pressure on standing, with resultant lightheadedness and risk of blackouts), and eventually constipation (due to decreased forward movement of intestinal contents). Some of the toxins (B and E) also precipitate nausea, vomiting, and difficulty with talking. The weakness then spreads to the arms (starting in the shoulders and proceeding to the forearms) and legs (again from the thighs down to the feet).
Synkinesis
Botox (botulinum toxin) is a new and versatile tool for the treatment of synkinesis. Initially used for reducing hyperkinesis after facial palsy, Botox was later attempted on patients with post-facial palsy synkinesis to reduce unwanted movements. The effects of Botox have shown to be remarkable, with synkinetic symptoms disappearing within 2 or 3 days. The most common treatment targets are the orbicularis oculi, depressor anguli oris (DAO), mentalis, platysma and the contralateral depressor labii inferioris muscles. Due to the short span of Botox effects though, patients must come back to the doctor for re-injection approximately every 3 months. More notable is that in a majority of patients, various synkinetic movements completely disappeared after 2-3 sessions of trimonthly Botox injections. 
A more specific synkinesis, crocodile tears syndrome (hyperlacrimation upon eating), has been shown to respond exceedingly well to Botox injection. Botox is injected directly into the lacrimal gland and has shown to reduce hyperlacrimation within 24–48 hours. The procedure was shown to be simple and safe with very little chance of side-effects (although on rare occasions ptosis can occur due to botulinum toxin diffusion). Furthermore, reduction in hyper-lacrimation was shown to last longer than the expected 3 months (about 12 months). 
Since Botox can mimic facial paralysis, an optimized dose has been determined that reduces involuntary synkinesis of the muscle while not affecting muscle tone.
Botulinum toxin
Botulism can be difficult to diagnose, as it may appear similar to diseases such as Guillain–Barré syndrome, myasthenia gravis, and stroke. 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 which 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 patients suffering from 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.
Clostridium botulinum
"C. botulinum" was first recognized and isolated in 1895 by Emile van Ermengem from home-cured ham implicated in a botulism outbreak. The isolate was originally named "Bacillus botulinus", after the Latin word for sausage, "botulus". ("Sausage poisoning" was a common problem in 18th- and 19th-century Germany, and was most likely caused by botulism) However, isolates from subsequent outbreaks were always found to be anaerobic spore formers, so Ida A. Bengtson proposed that the organism be placed into the genus "Clostridium", as the genus "Bacillus" was restricted to aerobic spore-forming rods.
Botulism
Infant botulism (also referred to as floppy baby syndrome) was first recognized in 1976, and is the most common form of botulism in the United States. Infants are susceptible to infant botulism in the first year of life, with more than 90% of cases occurring in infants younger than six months. Infant botulism results from the ingestion of the "C. botulinum" spores, and subsequent colonization of the small intestine. The infant gut may be colonized when the composition of the intestinal microflora (normal flora) is insufficient to competitively inhibit the growth of "C. botulinum" and levels of bile acids (which normally inhibit clostridial growth) are lower than later in life.
Clostridium botulinum
"C. botulinum" is responsible for foodborne botulism (ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming "C. botulinum"), and wound botulism (infection of a wound with "C. botulinum"). "C. botulinum" produces heat-resistant endospores that are commonly found in soil and are able to survive under adverse conditions.
Sixth nerve palsy
Other management options at this initial stage include the use of botulinum toxin, which is injected into the ipsilateral medial rectus (botulinum toxin therapy of strabismus). The use of BT serves a number of purposes. Firstly, it helps to prevent the contracture of the medial rectus which might result from its acting unopposed for a long period. Secondly, by reducing the size of the deviation temporarily it might allow prismatic correction to be used where this was not previously possible, and, thirdly, by removing the pull of the medial rectus it may serve to reveal whether the palsy is partial or complete by allowing any residual movement capability of the lateral rectus to operate. Thus, the toxin works both therapeutically, by helping to reduce symptoms and enhancing the prospects for fuller ocular movements post-operatively, and diagnostically, by helping to determine the type of operation most appropriate for each patient.
Botulism
Botulinum antitoxin consists of antibodies that neutralize botulinum toxin in the circulatory system by passive immunization. This prevents additional toxin from binding to the neuromuscular junction, but does not reverse any already inflicted paralysis.
Botulinum toxin
In cosmetic applications, botulinum toxin is considered safe and effective for reduction of facial wrinkles, especially in the uppermost third of the face. Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin. Smoothing of wrinkles is usually visible three days after treatment and is maximally visible two weeks following injection. The treated muscles gradually regain function, and generally return to their former appearance three to four months after treatment. Muscles can be treated repeatedly to maintain the smoothed appearance.
Botulinum toxin
Food-borne botulism results, indirectly, from ingestion of food contaminated with Clostridium spores, where exposure to an anaerobic environment allows the spores to germinate, after which the bacteria can multiply and produce toxin. Critically, "it is ingestion of toxin rather than spores or vegetative bacteria" that causes botulism. Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, and so is preventable. Infant botulism cases arise chiefly as a result of environmental exposure and are therefore more difficult to prevent. Infant botulism arising from consumption of honey can be prevented by eliminating honey from diets of children less than 12 months old.
Botulinum toxin
Botox has not been approved for any pediatric use. It has, however, been used off-label by physicians for several conditions. including spastic conditions in pediatric patients with cerebral palsy, a therapeutic course that has resulted in patient deaths. In the case of treatment of infantile esotropia in patients younger than 12 years of age, several studies have yielded differing results.
Myoclonic dystonia
Botulinum toxin injections also act upon acetylcholine to reduce dystonia symptoms. The neurotoxin is active in presynaptic terminals and blocks exocytosis of acetylcholine into the synaptic cleft which reduces muscle activity. Botulinum may also have a role in inhibiting glutamate and changing muscle movement. Studies have also shown possible axon transport of this neurotoxin as well as its function as a pain reliever without affect on overactive muscle movement in myoclonus dystonia patients.
Botulism
Botulism is generally treated with botulism antitoxin and supportive care.
Binding site
Competitive inhibitors are also largely found commercially. Botulinum toxin, known commercially as Botox, is a neurotoxin causes flaccid paralysis in the muscle due to binding to acetylcholine dependent nerves. This interaction inhibits muscle contractions, giving the appearance of smooth muscle.
Botulinum toxin therapy of strabismus
For patients who have had healthy vision heretofore until a small, horizontal deviation set in suddenly, the injection of botulinum toxin may allow them to maintain the binocular vision skills that had been acquired earlier.
Botulinum toxin
Since then, several randomized control trials have shown botulinum toxin type A to improve headache symptoms and quality of life when used prophylactically for patients with chronic migraine who exhibit headache characteristics consistent with: pressure perceived from outside source, shorter total duration of chronic migraines (<30 years), "detoxification" of patients with coexisting chronic daily headache due to medication overuse, and no current history of other preventive headache medications.
Foodborne illness
In addition to disease caused by direct bacterial infection, some foodborne illnesses are caused by enterotoxins (exotoxins targeting the intestines). Enterotoxins can produce illness even when the microbes that produced them have been killed. Symptom appearance varies with the toxin but may be rapid in onset, as in the case of enterotoxins of "Staphylococcus aureus" in which symptoms appear in one to six hours. This causes intense vomiting including or not including diarrhea (resulting in staphylococcal enteritis), and staphylococcal enterotoxins (most commonly staphylococcal enterotoxin A but also including staphylococcal enterotoxin B) are the most commonly reported enterotoxins although cases of poisoning are likely underestimated. It occurs mainly in cooked and processed foods due to competition with other biota in raw foods, and humans are the main cause of contamination as a substantial percentage of humans are persistent carriers of "S. aureus". The CDC has estimated about 240,000 cases per year in the United States.The rare but potentially deadly disease botulism occurs when the anaerobic bacterium "Clostridium botulinum" grows in improperly canned low-acid foods and produces botulin, a powerful paralytic toxin.
Vaginismus
Botulinum toxin A (Botox) has been considered as a treatment option, under the idea of temporarily reducing the hypertonicity of the pelvic floor muscles. Although no random controlled trials have been done with this treatment, experimental studies with small samples have shown it to be effective, with sustained positive results through 10 months. Similar in its mechanism of treatment, lidocaine has also been tried as an experimental option.
Clostridium botulinum
"C. botulinum" is an obligate anaerobe that is widely distributed in nature and is assumed to be present on all food surfaces. Its optimum growth temperature is within the mesophilic range. In spore form, it is the most heat resistant pathogen that can survive in low acid foods and grow to produce toxin. The toxin attacks the nervous system and will kill an adult at a dose of around 75 ng. This toxin is detoxified by holding food at 100 °C for 10 minutes.
Management of cerebral palsy
Dosages of botulin toxin have been based on expert opinion rather than evidence-based practices. The dosages recommended have recently been reduced to reduce severe side-effects including becoming sensitive to the botulin toxin and developing an allergic response. Higher risks have been noted with children who are at level IV and V on the GMFCS. A review on the treatment of drooling in children with cerebral palsy found that it was not possible to tell whether interventions worked or were safe, including botulin toxin A and benztropine and glycopyrrolate.
Botulinum toxin
The Japanese doomsday cult Aum Shinrikyo produced botulinum toxin and spread it as an aerosol in downtown Tokyo during the 1990s, but the attacks caused no fatalities.
Botulism
In adults, a trivalent antitoxin containing antibodies raised against botulinum toxin types A, B, and E is used most commonly, however a heptavalent botulism antitoxin has also been developed and was approved by the U.S. FDA in 2013. In infants, horse-derived antitoxin is sometimes avoided for fear of infants developing serum sickness or lasting hypersensitivity to horse-derived proteins. To avoid this, a human-derived antitoxin has been developed and approved by the U.S. FDA in 2003 for the treatment of infant botulism. This human-derived antitoxin has been shown to be both safe and effective for the treatment of infant botulism. However, the danger of equine-derived antitoxin to infants has not been clearly established, and one study showed the equine-derived antitoxin to be both safe and effective for the treatment of infant botulism.
Botulinum toxin
BTX-A is commonly used to treat cervical dystonia, but it can become ineffective after a time. Botulinum toxin type B (BTX-B) received FDA approval for treatment of cervical dystonia on December 21, 2000. Trade names for BTX-B are Myobloc in the United States, and Neurobloc in the European Union.
Botulism
Botulinum inhibits the release within the nervous system of acetylcholine, a neurotransmitter, responsible for communication between motor neurons and muscle cells. All forms of botulism lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, botulism leads to paralysis of the breathing muscles and causes respiratory failure. In light of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies, and public health officials are usually involved to identify the source and take steps to prevent further cases from occurring.
Botulism
"Clostridium botulinum" type C toxin has been incriminated as the cause of grass sickness, a condition in horses which occurs in rainy and hot summers in Northern Europe. The main symptom is pharynx paralysis.
Exogenous bacteria
Botulism is a rare disease caused by the bacterium "Clostridium botulinum."This microbe is primarily found in the soil or untreated water. Botulism spores can survive in unproperly canned or ill-prepared foods. Even ingesting trace amounts of the spores can lead to severe poisoning that causes symptoms such as vomiting, nausea, and even paralysis.
Spasmodic torticollis
Some patients experience or develop immunoresistance to botulinum toxin type A and must use botulinum toxin type B. Approximately 4% to 17% of patients develop botulinum toxin type A antibodies. The only botulinum toxin type B accessible in the United States is Myobloc. Treatment using botulinum toxin type B is comparable to type A, with an increased frequency of the side effect dry mouth.
Operation Anthropoid
The authors of "A Higher Form of Killing" claim that Heydrich died from botulism (botulinum poisoning). According to this theory, the No. 73 anti-tank hand grenade used in the attack had been modified to contain botulinum toxin, according Paul Fildes, a Porton Down botulism researcher. The authors say that there is only circumstantial evidence to support this allegation; the records of the SOE for the period have remained sealed and few medical records of Heydrich's condition and treatment have been preserved.
SNAP25
A genome wide association study pointed to the rs362584 polymorphism in the gene as possibly associated with the personality trait neuroticism. Botulinum toxins A, C and E cleave SNAP-25, leading to paralysis in clinically developed botulism.
Microbial toxin
Microbial toxins are toxins produced by micro-organisms, including bacteria and fungi. Microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Some bacterial toxins, such as "Botulinum" neurotoxins, are the most potent natural toxins known. However, microbial toxins also have important uses in medical science and research. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.
Flaccid paralysis
The "Clostridium botulinum" bacteria are the cause of botulism. Vegetative cells of "C. botulinum" may be ingested. Introduction of the bacteria may also occur via endospores in a wound. When the bacteria are in vivo, they induce flaccid paralysis. This happens because "C. botulinum" produces a toxin which blocks the release of acetylcholine. Botulism toxin blocks the exocytosis of presynaptic vesicles containing acetylcholine (ACh). When this occurs, the muscles are unable to contract. Other symptoms associated with infection from this neurotoxin include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Botulism prevents muscle contraction by blocking the release of acetylcholine, thereby halting postsynaptic activity of the neuromuscular junction. If its effects reach the respiratory muscles, then it can cause respiratory failure, leading to death.
Clostridium botulinum
The botulinum toxin can cause a severe flaccid paralytic disease in humans and other animals and is the most potent toxin known to mankind, natural or synthetic, with a lethal dose of 1.3–2.1 ng/kg in humans.
Hemiballismus
Botulinum Injections
New uses for botulinum toxin have included treatment of hemiballismus. However, this is still in the early stages of testing. This treatment deals with the muscular manifestations of hemiballismus as opposed to the neurological causes.
Botulinum toxin
BTX-A has also been used in the treatment of gummy 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 gingiva. Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the levator labii superioris (LLS), the levator labii superioris alaeque nasi muscle (LLSAN), and the zygomaticus minor (ZMi).
Botulinum toxin therapy of strabismus
The dosage to be used cannot be determined with precision, as no reliable relation between dose and effect could be established so far. The toxicity of botulinum toxin varies from one lot to the next; furthermore, the body may show an immunoreaction by which the efficacy of subsequent treatments is reduced.
Botulinum toxin
Besides the three primary U.S. manufacturers, there are numerous other botulinum toxin producers. Xeomin, manufactured in Germany by Merz, is also available for both therapeutic and cosmetic use in the U.S. Lanzhou Institute of Biological Products in China manufactures a BTX-A product; as of 2014 it was the only BTX-A approved in China. BTX-A is also sold as Lantox and Prosigne on the global market. Neuronox, a BTX-A product, was introduced by Medy-Tox Inc. of South Korea in 2009;
Botulism
The number of cases of food borne and infant botulism has changed little in recent years, but wound botulism has increased because of the use of black tar heroin, especially in California.
Spasmodic dysphonia
Botulinum toxin (Botox) is often used to improve some symptoms of spasmodic dysphonia through weakening or paralyzing the vocal folds, thus preventing muscle spasms. The level of evidence for its use is currently limited; little is known about optimal dosage, frequency of injections, or exact location of injection. However, it remains a choice for many people due to the predictability and low chance of long term side effects. It results in periods of some improvement, with the duration of benefit lasting for 10–12 weeks on average before symptoms return to baseline. Repeat injection is required to sustain good vocal production, as results are only temporary. Some transient side effects observed in adductor spasmodic dysphonia include reduced speaking volume, difficulty swallowing, and a breathy and hoarse voice quality. While treatment outcomes are generally positive, it is presently unclear whether this treatment approach is more or less effective than others.
Botulinum toxin therapy of strabismus
Botulinum toxin is considered as an alternative to surgery in certain clinical situations. A study performed in the 1980s found outcomes of surgery to be "more predictable and longer lasting" than those of botulinum toxin therapy. As stated in a review article of 2007, its use for strabismus "varies enormously in different cities and countries for no apparent reason."
Heptavalent botulism antitoxin
"HBAT" is derived from "despeciated" equine IgG antibodies, which have had the Fc portion cleaved off, leaving the F(ab') portions. This process renders it less efficacious at neutralizing toxin than the other product trivalent botulinum antitoxin (TBAT) available from local health departments (via the CDC) for treatment of wound and foodborne botulism. TBAT (effective against types A, B, and E) is derived from equine sources utilizing whole antibodies (Fab & Fc portions). But only "HBAT" is considered effective against all known strains of botulism (A, B, C, D, E, F, and G). These antitoxins neutralize only circulating toxin in patients with symptoms of botulism that are continuing to progress; they have no effect on toxin already bound to the nerve terminals. (This is not, however, considered a reason to withhold the product from any patient, even if treatment has been delayed.)
Neurotoxin
Botulinum Toxin (BTX) is a group of neurotoxins consisting of eight distinct compounds, referred to as BTX-A,B,C,D,E,F,G,H, which are produced by the bacterium "Clostridium botulinum" and lead to muscular paralysis. A notably unique feature of BTX is its relatively common therapeutic use in treating dystonia and spasticity disorders, as well as in inducing muscular atrophy despite being the most poisonous substance known. BTX functions peripherally to inhibit acetylcholine (ACh) release at the neuromuscular junction through degradation of the SNARE proteins required for ACh vesicle-membrane fusion. As the toxin is highly biologically active, an estimated dose of 1μg/kg body weight is sufficient to induce an insufficient tidal volume and resultant death by asphyxiation. Due to its high toxicity, BTX antitoxins have been an active area of research. It has been shown that capsaicin (active compound responsible for heat in chili peppers) can bind the TRPV1 receptor expressed on cholinergic neurons and inhibit the toxic effects of BTX.
Death Wish Coffee
In September 2017, Death Wish Coffee recalled its 11-ounce cans of Death Wish Nitro Cold Brew coffee. Concerns arose that their cold brewing process could allow the growth of "Clostridium botulinum", the bacterium responsible for botulism. No illnesses have been reported.
Canning
Foodborne botulism results from contaminated foodstuffs in which "C. botulinum" spores have been allowed to germinate and produce botulism toxin, and this typically occurs in canned non-acidic food substances that have not received a strong enough thermal heat treatment. "C. botulinum" prefers low oxygen environments and is a poor competitor to other bacteria, but its spores are resistant to thermal treatments. When a canned food is sterilized insufficiently, most other bacteria besides the "C. botulinum" spores are killed, and the spores can germinate and produce botulism toxin. Botulism is a rare but serious paralytic illness, leading to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. The botulinum toxin is extremely dangerous because it cannot be detected by sight or smell, and ingestion of even a small amount of the toxin can be deadly. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure. In view of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies, and public health officials are usually involved to prevent further cases from the same source.
Neuromuscular junction
Botulinum toxin (aka botulinum neurotoxin, BoNT, and sold under the trade name Botox) inhibits the release of acetylcholine at the neuromuscular junction by interfering with SNARE proteins. This toxin crosses into the nerve terminal through the process of endocytosis and subsequently interferes with SNARE proteins, which are necessary for ACh release. By doing so, it induces a transient flaccid paralysis and chemical denervation localized to the striated muscle that it has affected. The inhibition of the ACh release does not set in until approximately two weeks after the injection is made. Three months after the inhibition occurs, neuronal activity begins to regain partial function, and six months, complete neuronal function is regained.
Botulism
Other, much rarer sources of infection (about every decade in the US) include garlic or herbs stored covered in oil without acidification, chili peppers, improperly handled baked potatoes wrapped in aluminum foil, tomatoes, and home-canned or fermented fish.
Botulinum toxin
BTX-A is now a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such as cerebral palsy, for muscles with an impaired ability to effectively lengthen. Muscles affected by UMNS frequently are limited by weakness, loss of reciprocal inhibition, decreased movement control and hypertonicity (including spasticity). In January 2014, Botulinum toxin was approved by UK's Medicines and Healthcare Products Regulatory Agency (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.
SNARE (protein)
Botulinum Toxin (BoNT) is one of the most potent toxins to have ever been discovered. It is a proteolytic enzyme that cleaves SNARE proteins in neurons. Its protein structure is composed of two peptide subunits, a heavy chain (100kDas) and a light chain (50kDas), which are held together by a disulfide bond. The action of BoNT follows a 4-step mechanism including binding to the neuronal membrane, endocytosis, membrane translocation, and proteolysis of SNARE proteins.
Toxin
Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to almost immediately deadly (such as botulinum toxin).
Botulinum toxin therapy of strabismus
Botulinum toxin has also been used postoperatively for improving the alignment in patients with over- or undercorrection after strabismus surgery, leading to rapid elimination of postoperative diplopia but possibly requiring repeated injections or reoperation later on. It is considered particularly useful for patients who have the potential for binocular vision; success rates are higher for treating postoperative esotropia than for treating postoperative exotropia.
Acetylcholine
Botulinum toxin (Botox) acts by suppressing the release of acetylcholine, whereas the venom from a black widow spider (alpha-latrotoxin) has the reverse effect. ACh inhibition causes paralysis. When bitten by a black widow spider, one experiences the wastage of ACh supplies and the muscles begin to contract. If and when the supply is depleted, paralysis occurs.
Clostridium botulinum
In the case of a diagnosis or suspicion of botulism, patients should be hospitalized immediately, even if the diagnosis and/or tests are pending. If botulism is suspected, patients should be treated immediately with antitoxin therapy in order to reduce mortality. Immediate intubation is also highly recommended, as respiratory failure is the primary cause of death from botulism.
Microbial toxin
"Botulinum" neurotoxins (BoNTs) are the causative agents of the deadly food poisoning disease botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production. They also serve as powerful tools to treat an ever expanding list of medical conditions.
Botulinum toxin
Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, 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 strabismus surgery 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 Daniel Drachman’s work with chicks at Johns Hopkins, Alan B. Scott 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.
Botulinum toxin
William J. Binder reported in 2000 that patients 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 it is now known that the toxin inhibits release of peripheral nociceptive neurotransmitters, suppressing the central pain processing systems responsible for migraine headache.
Botulinum toxin therapy of strabismus
Botulinum toxin therapy of strabismus is a medical technique used sometimes in the management of strabismus, in which botulinum toxin is injected into selected extraocular muscles in order to reduce the misalignment of the eyes. The injection of the toxin to treat strabismus, reported upon in 1981, is considered to be the first ever use of botulinum toxin for therapeutic purposes. Today, the injection of botulinum toxin into the muscles that surround the eyes is one of the available options in the management of strabismus. Other options for strabismus management are vision therapy and occlusion therapy, corrective glasses (or contact lenses) and prism glasses, and strabismus surgery.
Botulinum toxin
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, patients who had come to rely on periodic injections became desperate. For 4 months, as liability issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.
Botulism
The paralysis caused by botulism can persist for 2 to 8 weeks, during which supportive care and ventilation may be necessary to keep the person alive. Botulism is fatal in 5% to 10% of people who are affected. However, if left untreated, botulism is fatal in 40% to 50% of cases.
Botulism
The most common form in Western countries is infant botulism. This occurs in infants who are colonized with the bacterium in the small intestine during the early stages of their lives. The bacterium then produces the toxin, which is absorbed into the bloodstream. The consumption of honey during the first year of life has been identified as a risk factor for infant botulism; it is a factor in a fifth of all cases. The adult form of infant botulism is termed "adult intestinal toxemia", and is exceedingly rare.
Botulinum toxin
As of 2013, botulinum toxin injections are the most common cosmetic operation, with 6.3 million procedures in the United States, according to the American Society of Plastic Surgeons. Qualifications for Botox injectors vary by county, state and country. Botox cosmetic providers include dermatologists, plastic surgeons, aesthetic spa physicians, dentists, nurse practitioners, nurses and physician assistants.
Natural product
Although most of the drugs derived from bacteria are employed as anti-infectives, some have found use in other fields of medicine. Botulinum toxin (from "Clostridium botulinum") and bleomycin (from "Streptomyces verticillus") are two examples. Botulinum, the neurotoxin responsible for botulism, can be injected into specific muscles (such as those controlling the eyelid) to prevent muscle spasm. Also, the glycopeptide bleomycin is used for the treatment of several cancers including Hodgkin's lymphoma, head and neck cancer, and testicular cancer. Newer trends in the field include the metabolic profiling and isolation of natural products from novel bacterial species present in underexplored environments. Examples include symbionts or endophytes from tropical environments, subterranean bacteria found deep underground via mining/drilling, and marine bacteria.
Botulinum toxin
The cosmetic effect of BTX-A on wrinkles was originally documented by a plastic surgeon from Sacramento, California, Richard Clark, and published in the journal "Plastic and Reconstructive Surgery" in 1989. Canadian husband and wife ophthalmologist and dermatologist physicians, JD and JA Carruthers, were the first to publish a study on BTX-A for the treatment of glabellar frown lines in 1992. Similar effects had reportedly been observed by a number of independent groups (Brin, and the Columbia University group under Monte Keen.) After formal trials, on April 12, 2002, the FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). Subsequently, cosmetic use of botulinum toxin type A has become widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US Food and Drug Administration approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.
Clostridium botulinum
Most strains produce one type of neurotoxin, but strains producing multiple toxins have been described. "C. botulinum" producing B and F toxin types have been isolated from human botulism cases in New Mexico and California. The toxin type has been designated Bf as the type B toxin was found in excess to the type F. Similarly, strains producing Ab and Af toxins have been reported. Evidence indicates the neurotoxin genes have been the subject of horizontal gene transfer, possibly from a viral source. This theory is supported by the presence of integration sites flanking the toxin in some strains of "C. botulinum". However, these integrations sites are degraded, indicating that the "C. botulinum" acquired the toxin genes quite far in the evolutionary past.