Who first discovered Botulinum toxin?
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.
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.
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.
Tetrodotoxin
The toxin was first isolated and named in 1909 by Japanese scientist Dr. Yoshizumi Tahara. It was one of the agents studied by Japan's Unit 731, which evaluated biological weapons on human subjects in the 1930s.
Frances Meehan Latterell
Frances Meehan Latterell (December 21, 1920 – November 5, 2008) was an American plant pathologist whose research in the late 1940s opened a major new area of inquiry into the physiological basis of plant disease. She was the senior author on a classic 1947 paper showing that the toxin victorin, produced by the pathogenic fungus "Helminthosporium victoriae", caused symptoms of Victoria blight of oats, a new disease first described by Latterell and her major professor in 1946. This discovery of a host-specific toxin, as victorin was later named, gave scores of subsequent researchers new model systems for studying plant disease.
Tuberculin
Tuberculin was discovered by German scientist and physician Robert Koch in 1890. The original tuberculin discovered by Koch was a glycerine extract of the tubercle bacilli and was developed as a remedy for tuberculosis, but reductions in deaths did not meet those expected of the treatment. British efforts to set up 'dispensaries' for the examination, diagnosis and treatment of the poor achieved better results as the Edinburgh System structure encompassed treatment of the homes and entire contacts of the TB sufferers. The example of Dr Hilda Clark's dispensary at Street, Somerset was especially marked for its efficacious treatment of the less severe cases. Clemens von Pirquet, an Austrian physician, discovered that patients who had previously received injections of horse serum or smallpox vaccine had quicker, more severe reactions to a second injection, and he coined the word "allergy" to describe this hypersensitivity reaction. Soon thereafter von Pirquet discovered the same type of reaction took place in those infected with tuberculosis, and he thus found the utility of what would become the tuberculin skin test. Individuals with active tuberculosis were usually tuberculin positive, but many of those with disseminated and rapidly progressive of disease were negative. This led to the widespread but erroneous belief that tuberculin reactivity is an indicator of immunity to tuberculosis.
History of malaria
Austrian chemist Othmar Zeidler is credited with the first synthesis of DDT (DichloroDiphenylTrichloroethane) in 1874. The insecticidal properties of DDT were identified in 1939 by chemist Paul Hermann Müller of Geigy Pharmaceutical. For his discovery of DDT as a contact poison against several arthropods, he was awarded the 1948 Nobel Prize in Physiology or Medicine. In the fall of 1942, samples of the chemical were acquired by the United States, Britain and Germany. Laboratory tests demonstrated that it was highly effective against many insects.
Cholera toxin
Cholera toxin was discovered in 1959 by Indian microbiologist Sambhu Nath De
Estrone
Estrone was the first steroid hormone to be discovered. It was discovered in 1929 independently by the American scientists Edward Doisy and Edgar Allen and the German biochemist Adolf Butenandt, although Doisy and Allen isolated it two months before Butenandt. They isolated and purified estrone in crystalline form from the urine of pregnant women. Doisy and Allen named it "theelin", while Butenandt named it "progynon" and subsequently referred to it as "folliculin" in his second publication on the substance. Butenandt was later awarded the Nobel Prize in 1939 for the isolation of estrone and his work on sex hormones in general. The molecular formula of estrone was known by 1931, and its chemical structure had been determined by Butenandt by 1932. Following the elucidation of its structure, estrone was additionally referred to as "ketohydroxyestrin" or "oxohydroxyestrin", and the name "estrone", on the basis of its C17 ketone group, was formally established in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London.
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.
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.
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.
Robert Koch
During his time as the government advisor with the Imperial Department of Health in Berlin in the 1880s, Robert Koch became interested in tuberculosis research. At the time, it was widely believed that tuberculosis was an inherited disease. However, Koch was convinced that the disease was caused by a bacterium and was infectious, and tested his four postulates using guinea pigs. Through these experiments, he found that his experiments with tuberculosis satisfied all four of his postulates. In 1882, he published his findings on tuberculosis, in which he reported the causative agent of the disease to be the slow-growing "Mycobacterium tuberculosis". Later, Koch's attempt at developing a drug to treat tuberculosis, tuberculin, led to a scandalous failure: he did not divulge the exact composition, and the claimed treatment success did not materialize; the substance is today used for tuberculosis diagnosis.
Justinus Kerner
Justinus Andreas Christian Kerner (18 September 1786, in Ludwigsburg, Baden-Württemberg, Germany – 21 February 1862, in Weinsberg, Baden-Württemberg) was a German poet, practicing physician, and medical writer. He gave the first detailed description of botulism.
Fredric Brandt
Fredric Sheldon Brandt (June 26, 1949 – April 5, 2015) was an American physician, researcher, lecturer, author, and radio host specializing in cosmetic dermatology. Among the first to use botulinum toxin ("botox") and fillers, Brandt was noted for his role in the FDA approval of numerous fillers and botulinum toxins for cosmetic use in the United States.
Neuromuscular junction
Tetanus toxin, also known as tetanospasmin is a potent neurotoxin produced by "Clostridium tetani" and causes the disease state, tetanus. The LD of this toxin has been measured to be approximately 1 ng/kg, making it second only to Botulinum toxin D as the deadliest toxin in the world. It functions very similarly to botunlinum neurotoxin (BoNT) by attaching and endocytosing into the presynaptic nerve terminal and interfering with SNARE protein complexes. It differs from BoNT in a few ways, most apparently in its end state, wherein tetanospasmin demonstrates a rigid / spastic paralysis as opposed to the flaccid paralysis demonstrated with BoNT.
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.
Robert R. Williams
Robert Runnels Williams (February 16, 1886 – October 2, 1965) was an American chemist, known for being the first to chemically fully characterize and then synthesize thiamine (vitamin B). He first isolated thiamine in 1933, and synthesized vitamin B in 1935, reporting this in 1936. Williams also provided the modern name "thiamine" from the molecule's sulfur atom, and it being a vitamin (a class ultimately named for the earlier-known amine of thiamine itself).
Botulinum toxin
Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including post-stroke spasticity, post-spinal cord injury spasticity, spasms of the head and neck, eyelid, vagina, limbs, jaw, and vocal cords. Similarly, botulinum toxin is used to relax clenching of muscles, including those of the oesophagus, jaw, lower urinary tract and bladder, or clenching of the anus which can exacerbate anal fissure. It may also be used for improper eye alignment. Botulinum toxin appears to be effective for refractory overactive bladder.
Gordon Alles
Gordon A. Alles (November 26, 1901 – January 21, 1963), was an American chemist and pharmacologist who did much research on the isolation and properties of insulin for the treatment of diabetics. He is also credited with discovering and publishing the psychological effects of amphetamine, and for methylenedioxyamphetamine (MDA). He is the first person to have prepared amphetamine sulfate, although not the amphetamine molecule. Alles first reported the physiological properties amphetamine as a synthetic analog of ephedrine, and therefore received credit for this discovery. He enjoyed large royalties from Smith, Kline & French (SKF) because he sold his patent rights for amphetamine to the company and it enjoyed large sales. Several popular products sold by SKF contained amphetamine including Benzedrine pills and inhalers, Dexedrine pills, and Dexamyl tablets. Counterfeit drugs appeared, trying to violate Alles' 'weak' patent, e.g., "Profetamine".
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.
Botulinum toxin
In response to the occurrence of these side effects, in 2008 the U.S. Food and Drug Administration notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, they warned that the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating 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. Additionally, the FDA announced name changes to several botulinum toxin products, meant to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were renamed "onabotulinumtoxinA", Myobloc was renamed "rimabotulinumtoxinB", and Dysport name renamed "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 Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.
Botulinum toxin
Based on data from thousands of patients collected by 240 investigators, Allergan received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and blepharospasm, using the trademark Botox. This was under the 1983 US Orphan Drug Act.
Cyril Norman Hugh Long
In the 1930s and 1940s Long and Abraham White worked together in the Yale Medical Center. As a result of their work in 1937 they isolated bovine prolactin, the first of the protein pituitary hormones to be obtained in pure crystalline form. Later, they isolated different hormones, and later characterized and sequenced many of them, greatly contributing to modern biochemistry. Long mainly worked with the hormones of the pituitary gland and adrenal extracts of the metabolism; his major research goal was to find a cure for diabetes.
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.
Tuberculosis
Robert Koch identified and described the bacillus causing tuberculosis, "M. tuberculosis", on 24 March 1882. He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Koch did not believe the cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. During the first half of the 1900s the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". While it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis. World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement.
Peter Ludvig Panum
From 1855 he was a professor at the University of Kiel, where he established a laboratory for physiology. Troubled by anti-Danish sentiment at Kiel, he relocated to the University of Copenhagen during 1862, where he spent the remainder of his career. Among his students at Copenhagen were physiologist Christian Bohr (1855-1911) and zymologist Emil Christian Hansen (1842-1909). 
Panum is acknowledged as being the first person to perform systematic and scientific studies of endotoxin, a substance once referred to as "putrid poison" that was thought to be responsible for symptoms and signs observed in individuals with sepsis.
Botulinum toxin
Botulinum toxin A is marketed under the brand names Botox and Xeomin. Botulinum toxin B is marketed under the brand name Myobloc.
Botulinum toxin therapy of strabismus
Alan B. Scott first injected botulinum toxin into extraocular muscles since the early 1970s and published his results 1981, giving rise to a wide scope of clinical research on the use of the toxin.
Botulinum toxin
Proper refrigeration at temperatures below 3 °C (38 °F) retards the growth of "Clostridium botulinum". 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.
Ida A. Bengtson
Bengtson's most significant scientific achievement was in regards to an organism called Clostridium botulinum, which causes a paralytic disease in chicken. This organism 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 Bengtson proposed that the organism be placed in the genus "Clostridium" as the "Bacillus" genus was restricted to aerobic spore-forming rods.
Botulinum toxin
In 1820, Justinus Kerner, a small-town German medical officer and romantic poet, gave the first complete description of clinical botulism based on extensive clinical observations of so-called “sausage poisoning”. Following experiments on animals and on himself, he concluded that the toxin acts by interrupting signal transmission in the somatic and autonomic motor systems, without affecting sensory signals or mental functions. He observed that the toxin develops under anaerobic conditions, and can be lethal in minute doses. His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.
Treat Baldwin Johnson
Johnson was the editor of the owner's manual for A. C. Gilbert Company's chemistry sets. He, together with R.D. Coghill, was the first to discover the existence of 5-Methylcytosine in nature, from tuberculinic acid, a nucleotide of Mycobacterium tuberculosis.
Botulinum toxin
Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (A,B,E) botulinum antitoxin is derived from equine sources using whole antibodies. The second antitoxin is Heptavalent (A,B,C,D,E,F,G) botulinum antitoxin, which is derived from equine antibodies which have been altered to make them less immunogenic. This antitoxin is effective against all known strains of botulism.
William Hallock Park
In 1893, Dr. Hermann Biggs, Professor of Bacteriology at New York University and Chief Inspector of the New York City Board of Health, offered Park a director's position in the municipal laboratories to continue his work on diphtheria. In 1894, Dr. Biggs telegraphed Park with the news of the discovery of the diphtheria antitoxin by Drs. Emile Roux and Emil von Behring and instructed him to begin inoculating horses to produce antitoxin in New York City. The atypical strain of "Corynebacterium diphtheriae" most widely used for the production of diphtheria toxin was discovered by Dr. Anna Williams, who worked with Dr. Park.
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
Botulinum toxin
Botulinum toxin is used to treat a number of problems.
Botulinum toxin
The drug is under development for the treatment of premature ejaculation.
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.
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.
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).
Botulinum toxin
Marrying ophthalmology to dermatology, Jean and Alistair Carruthers observed that blepharospasm patients who received injections around the eyes and upper face also enjoyed diminished facial glabellar lines (“frown lines” between the eyebrows), thereby initiating the highly-popular cosmetic use of the toxin. Brin, and a group at Columbia University under Monte Keen made similar reports. In 2002, following clinical trials, the FDA approved Botox Cosmetic, botulinum A toxin to temporarily improve the appearance of moderate-to-severe glabellar lines. The FDA approved a fully "in vitro" assay for use in the stability and potency testing of Botox in response to increasing public concern that LD50 testing was required for each batch sold in the market.
Batrachotoxin
It was named by scientists John W. Daly and Bernhard Witkop, who separated the potent toxic alkaloids fraction and determined its chemical properties. They isolated four major toxic steroidal alkaloids including batrachotoxin, isobatrachotoxin, pseudobatrachotoxin, and batrachotoxinin A. Due to the difficulty of handling such a potent toxin and the minuscule amount that could be collected, a comprehensive structure determination involved several difficulties. However, Takashi Tokuyama, who joined the investigation later, converted one of the congener compounds, Batrachotoxinin A, to a crystalline derivative and its unique steroidal structure was solved with x-ray diffraction techniques (1968). When the mass spectrum and NMR spectrum of batrachotoxin and the batrachotoxinin A derivatives were compared, it was realized that the two shared the same steroidal structure and that batrachotoxin was batrachotoxinin A with a single extra pyrrole moiety attached. In fact, batrachotoxin was able to be partially hydrolyzed using sodium hydroxide into a material with identical TLC and color reactions as batrachotoxinin A. The structure of batrachotoxin was established in 1969 through chemical recombination of both fragments. Batrachotoxinin A was synthesized by Michio Kurosu, Lawrence R. Marcin, Timothy J. Grinsteiner, and Yoshito Kishi in 1998.
Paul Ehrlich
As a model for experimental therapy Ehrlich used a guinea pig disease trypanosoma and tested out various chemical substances on laboratory animals. The trypanosomes could indeed be successfully killed with the dye trypan red. Beginning in 1906, he intensively investigated atoxyl and had it tested by Robert Koch along with other arsenic compounds during Koch's sleeping sickness expedition of 1906/07. Although the name literally means “nonpoisonous,” atoxyl does cause damage, especially to the optic nerve. Ehrlich elaborated the systematic testing of chemical compounds in the sense of screening as now practiced in the pharmaceutical industry. He discovered that Compound 418 - Arsenophenylglycine - had an impressive therapeutic effect and had it tested in Africa.
Pertussis toxin
PT clearly plays a central role in the pathogenesis of pertussis although this was discovered only in the early 1980s. The appearance of pertussis is quite recent, compared with other epidemic infectious diseases. The earliest mention of pertussis, or whooping cough, is of an outbreak in Paris in 1414. This was published in Moulton’s The Mirror of Health, in 1640. Another epidemic of pertussis took place in Paris in 1578 and was described by a contemporary observer, Guillaume de Baillou. Pertussis was well known throughout Europe by the middle of the 18th century. Jules Bordet and Octave Gengou described in 1900 the finding of a new “ovoid bacillus” in the sputum of a 6-month-old infant with whooping cough. They were also the first to cultivate "Bordetella pertussis" at the Pasteur Institute in Brussels in 1906.
Instituto Butantan
The Institute was founded by the Brazilian physician and biomedical scientist Vital Brazil in 1901, according to Pasteur Institute paradigm, i.e., by combining in the same institution medical research, the transfer of the results to society as health products, and self-financing through this later activity. Its foundation was a reaction to the outbreak of bubonic plague in the city of Santos. It is internationally renowned for its research on venomous animals; it was visited by Theodore Roosevelt in 1912. It is also a state-supported producer of vaccines against many infectious diseases, such as rabies, hepatitis, botulism, tetanus, diphtheria, pertussis and tuberculosis, as well as polyvalent and monovalent antivenoms against the bites of snakes, lizards, bees, scorpions and spiders (which, historically were first developed in the beginning of the 20th century by Dr. Vital Brazil and his coworkers). Among the distinguished scientists at the institute were biochemists Karl Slotta and Heinz Fraenkel-Conrat, pioneers in the study of progesterone, estriol, and medical use of venom, from 1935 to 1948.
Redi Award
"Osservazioni intorno alle vipere" ("Observations about the Viper") written by an Italian polymath Francesco Redi in 1664 is regarded as the milestone in the beginning of toxinology research. Redi was the first scientist to elucidate the scientific basis of snakebite and venom of the viper. He showed for the first time that the viper venom comes from the fang, not the gallbladder as it was believed; that it is not poisonous when swallowed, and effective only when it enters the bloodstream. He even demonstrated the possibility of slowing down the venom action in the blood by tight ligature before the wound. This work is heralded as the foundation of toxinology. In honour of the pioneer, the International Society on Toxinology (ISI) instituted the "Redi Award" in 1967 in recognition of scientists for their significant contributions in toxinology research.
Insulin
On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were cancelled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract. A second dose was injected on January 23, completely eliminating the glycosuria that was typical of diabetes without causing any obvious side-effects. The first American patient was Elizabeth Hughes, the daughter of U.S. Secretary of State Charles Evans Hughes. The first patient treated in the U.S. was future woodcut artist James D. Havens; Dr. John Ralston Williams imported insulin from Toronto to Rochester, New York, to treat Havens.
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.
Botulinum toxin
Onabotulinumtoxin A (trade name Botox) received FDA approval for treatment of chronic migraines on October 15, 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 migraine sufferers undergoing the Botox treatment.
Botulinum toxin
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick 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 Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and generously provided it to the academic community.
Botulinum toxin
In December 1989, Botox was approved by the US Food and Drug Administration (FDA) for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients over 12 years old.
Maurício Rocha e Silva
Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, Rocha e Silva discovered in 1948 the powerful hypotensive effects of bradykinin in animal preparations. Bradykinin was detected in the plasma of animals after the addition of venom of "Bothrops jararaca" (Brazilian lancehead snake), which was brought by Rosenfeld from the Butantan Institute, in São Paulo, Brazil. This discovery was part of a continuing study on circulatory shock and proteolytic enzymes related to the toxicology of snake bites, started by Rocha e Silva as early as 1939. Bradykinin was to be proved a new autopharmacological principle, i.e., a substance that is released in the body by a metabolic modification from precursors, which are pharmacologically active. According to B.J. Hagwood, Rocha e Silva's biographer, "The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins."
Botulinum toxin
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. Karl Friedrich Meyer, a prodigiously productive 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.
Niacin
Niacin was first described by chemist Hugo Weidel in 1873 in his studies of nicotine. The original preparation remains useful: the oxidation of nicotine using nitric acid. For the first time, niacin was extracted by Casimir Funk, but he thought that it was thiamine and due to the discovered amine group he coined the term "vitamine". Niacin was extracted from livers by biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor." Soon after, in studies conducted in Alabama and Cincinnati, Dr. Tom Spies found that nicotinic acid cured the sufferers of pellagra.
Neurotoxin
As neurotoxins are compounds which adversely affect the nervous system, a number of mechanisms through which they function are through the inhibition of neuron cellular processes. These inhibited processes can range from membrane depolarization mechanisms to inter-neuron communication. By inhibiting the ability for neurons to perform their expected intracellular functions, or pass a signal to a neighboring cell, neurotoxins can induce systemic nervous system arrest as in the case of botulinum toxin, or even nervous tissue death. The time required for the onset of symptoms upon neurotoxin exposure can vary between different toxins, being on the order of hours for botulinum toxin and years for lead.
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).
Raymond C. Stevens
In 1992, Stevens worked with researchers at Gilead on the structural studies of neuraminidase inhibitors that eventually became Tamiflu, and later partnered with Roche. After the initial experience with structure based drug discovery from 1992–1997 with Gilead and Tamiflu, Stevens focused on understanding the basic mechanism of how Botox (botulinum toxin) works, and on ways to use this scaffold for next generation protein therapeutics. In parallel to the work on botulinum toxin, Stevens worked on the enzymes involved in the catecholamine biosynthetic pathway, specifically the three aromatic amino acid hydroxylases including phenylalanine hydroxylase. From 1999-2004 Stevens was involved in the startup of Syrrx that developed the marketed drug Nesina for type II diabetes. From 2000–2010, Stevens has worked with BioMarin Pharmaceutical to develop Kuvan (tetrahydrobiopterin) and assisted in the design and development of PEG-PAL (pegylated Phenylalanine ammonia-lyase) as treatments for mild and classical phenylketonuria (PKU). In 2008 Stevens started Receptos that developed an S1P1 agonist for multiple sclerosis and inflammatory bowel disease and in 2011 he started RuiYi that developed an anti-CB1 antibody for liver fibrosis.
Alexandre Yersin
Yersin was born in 1863 in Aubonne, Canton of Vaud, Switzerland, to a family originally from France. From 1883 to 1884, Yersin studied medicine at Lausanne, Switzerland; and then at Marburg, Germany and Paris (1884–1886). In 1886, he entered Louis Pasteur's research laboratory at the École Normale Supérieure, by invitation of Emile Roux, and participated in the development of the anti-rabies serum. In 1888 he received his doctorate with a dissertation titled "Étude sur le Développement du Tubercule Expérimental" and spent two months with Robert Koch in Germany. He joined the recently created Pasteur Institute in 1889 as Roux's collaborator and discovered with him the diphtheric toxin (produced by the "Corynebacterium diphtheriae" bacillus).
Butantoxin
Butantoxin is one of multiple toxins isolated from the venom of three Brazilian and one Argentinean scorpion species of the genus "Tityus": "T. serrulatus", "T. bahiensis", "T. stigmurus" and "T. trivitattus". Butantoxin was the first isolated scorpion toxin (identical primary structure and folding) found to be produced by more than one scorpion species. Previously studied toxin sequences varied between different species within a genus.
Norboletone
In 2002, Don Catlin, the founder and then-director of the UCLA Olympic Analytical Lab, identified norboletone for the first time in an athlete’s urine sample. In the same year, U.S. bicycle racer Tammy Thomas was caught using it and was banned from her sport. The following year, Catlin identified and developed a test for tetrahydrogestrinone (THG), the second reported designer anabolic sample—a key development in the BALCO Affair.
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.
Orellanine
It wasn't until 1962 until the first isolation of orellanine was done. The first methanolic extraction and isolation of orellanine was done by Stanisław Grzymala and isolated from the mushroom "Cortinarius orellanus". Along with the isolation of orellanine, Grzymala was also able to demonstrate the nephrotoxicity of "Cortinarius orellanus" and determine various physical and chemical properties of orellanine. He found that the toxicity of the mushrooms was linked to delayed and acute renal failure, as well as when the isolated white crystalline substance was heated above 150 ̊C it began to slowly decompose. After this first isolation of orellanine, the structure of orellanine was first discovered by Antkowiak and Gessner in 1979. Orellanine’s structure was found to be 3,3',4,4'-tetrahydroxy- 2,2'-bipyridine-l,l'-dioxide. Antkowiak and Gessner were also able to determine that orellanine was the mono-N-oxide of orelline, which was the decomposition product of orellanine. It was also found that orelline was non-toxic. The first successful synthesis of orellanine was done in 1985. Tiecco, M. et. Al. completed a total synthesis of orellanine using commercially available 3-hydroxypyridine. After the first successful synthesis, the structure was confirmed in 1987 by Cohen-Addad et al. in 1987 by X-ray crystallography.
Botulism
Botulinum toxin is broken into 8 neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. Types C and D cause toxicity only in other animals.
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
In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache.
Anal fissure
A combined surgical and pharmacological treatment, administered by colorectal surgeons, is direct injection of botulinum toxin (Botox) into the anal sphincter to relax it. This treatment was first investigated in 1993. However, in many cases involving Botox injections the patients eventually had to choose another cure as the injections proved less and less potent, spending thousands of dollars in the meantime for a partial cure. Lateral sphincterotomy is the Gold Standard for curing this affliction.
Combination of medical therapies may offer up to 98% cure rates.
AB5 toxin
This family is also known as Ptx and contains the toxin responsible for whooping cough. Pertussis toxin is secreted by the gram-negative bacterium, "Bordetella pertussis". Whooping cough is very contagious and cases are slowly increasing in the United States despite vaccination. Symptoms include paroxysmal cough with whooping and even vomiting. The bacterium "Bordetella pertussis" was first identified as the cause of whooping cough and isolated by Jules Bordet and Octave Gengou in France in 1900.
Bodog F. Beck
Bodog Felix Beck (1871 – 1 January 1942) was a Hungarian-born American physician who specialized in the treatment of arthritic and rheumatoid conditions using bee venom and who coined the term "bee venom therapy". There are no studies proving the ability of bee venom to cure any ailment.
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.
AB5 toxin
This family is also known as Ct or Ctx, and includes the heat-labile enterotoxin family, known as LT. Cholera toxin’s discovery is credited by many to Dr. Sambhu Nath De. He conducted his research in Calcutta (now Kolkata) making his discovery in 1959, although it was first purified by Robert Koch in 1883. Cholera toxin is composed of a protein complex that is secreted by the bacterium "Vibrio cholerae". Some symptoms of this toxin include chronic and widespread watery diarrhea and dehydration that, in some cases, leads to death.
Red Army Faction
During the early-1980s, German and French newspapers reported that the police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that contained flasks full of "Clostridium botulinum", which makes botulinum toxin. These reports were later found to be incorrect; no such lab was ever found.
Heptavalent botulism antitoxin
The Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine) (BAT) – BAT, made by Emergent BioSolutions Canada Inc. (formerly Cangene Corporation), – is a licensed, commercially available botulism anti-toxin that effectively neutralizes all seven known botulinum nerve toxin serotypes (types A, B, C, D, E, F and G). It is indicated for sporadic cases of life-threatening botulism and is also stockpiled for the eventuality of botulinum nerve toxins being used in a future bioterrorist attack.
DDT
Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochlorine, originally developed as an insecticide, and ultimately becoming infamous for its environmental impacts. It was first synthesized in 1874 by the Austrian chemist Othmar Zeidler. DDT's insecticidal action was discovered by the Swiss chemist Paul Hermann Müller in 1939. DDT was used in the second half of World War II to control malaria and typhus among civilians and troops. Müller was awarded the Nobel Prize in Physiology or Medicine "for his discovery of the high efficiency of DDT as a contact poison against several arthropods" in 1948.
Botulinum toxin
With regard to detection, current protocols using NBC 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 of human biological fluids; serum levels of 12–24 mouse LD units per milliliter have been detected in poisoned patients.
Cytolethal distending toxin
The first recorded observation of a cytolethal-distending toxin was in 1987 in a pathogenic strain in "E. coli" isolated from a young patient. Later that year, scientists W.M. Johnson and H. Lior published the journal article “Production of Shiga toxin and a cytolethal distending toxin (CLDT) by serogroups of "Shigella spp."” In "Microbiology Letters". The discovery of other bacteria producing CDT toxins continues to this day.
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.
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.
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.
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.
Nomenclature of monoclonal antibodies
Emil von Behring and Kitasato Shibasaburō discovered in 1890 that diphtheria and tetanus toxins were neutralized in the bloodstream of animals by substances they called "antitoxins", which were specific for the respective toxin. Behring received the first Nobel Prize in Physiology or Medicine for their find in 1901. A year after the discovery, Paul Ehrlich used the term "antibodies" (German "Antikörper") for these antitoxins.
Botulinum toxin
The seven toxin types (A-G) 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 serotypes cause human botulism, with the activities of types A and B enduring longest "in vivo" (from several weeks to months).
Passive immunity
In 1888 Emile Roux and Alexandre Yersin showed that the clinical effects of diphtheria were caused by diphtheria toxin and, following the 1890 discovery of an antitoxin-based immunity to diphtheria and tetanus by Emil Adolf von Behring and Kitasato Shibasaburō, antitoxin became the first major success of modern therapeutic immunology. Shibasaburo and von Behring immunized guinea pigs with the blood products from animals that had recovered from diphtheria and realized that the same process of heat treating blood products of other animals could treat humans with diphtheria. By 1896, the introduction of diphtheria antitoxin was hailed as "the most important advance of the [19th] Century in the medical treatment of acute infective disease".
Bradykinin
Bradykinin was discovered in 1948 by three Brazilian physiologists and pharmacologists working at the Instituto Biológico, in São Paulo, Brazil, led by Dr. Maurício Rocha e Silva. Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, they discovered the powerful hypotensive effects of bradykinin in animal preparations. Bradykinin was detected in the blood plasma of animals after the addition of venom extracted from the "Bothrops jararaca" (Brazilian lancehead snake), brought by Rosenfeld from the Butantan Institute. The discovery was part of a continuing study on circulatory shock and proteolytic enzymes related to the toxicology of snake bites, started by Rocha e Silva as early as 1939. Bradykinin was to prove a new autopharmacological principle, i.e., a substance that is released in the body by a metabolic modification from precursors, which are pharmacologically active. According to B.J. Hagwood, Rocha e Silva's biographer, "The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins." Etymology: brady [Gk] slow, kinin [Gk ] kīn(eîn) to move, set in motion, ? from the effect of snake venom on intestinal smooth muscle, which was noted to slowly contract.
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.
Émile van Ermengem
Émile Pierre-Marie van Ermengem (1851–1932, or 1851–1922 according to some sources) was a Belgian bacteriologist who, in 1895, isolated "Clostridium botulinum", the bacterium that causes botulism, from a piece of ham that had poisoned thirty four people.
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.
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.
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.
Botulinum toxin
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 and can be instantaneous. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.
Betulin
Betulin was discovered in 1788 by German-Russian chemist Johann Tobias Lowitz.
The Satan Bug (novel)
During the theft the current head of security is killed with a cyanide-laced sweet, presumably given to him by an insider he trusted. A variety of scientists and support staff come under suspicion, and it emerges that several of them have been coerced by blackmail or kidnapping to help the principal villain, without knowing his identity. The villain releases botulinum toxin over an evacuated area of East Anglia, killing hundreds of livestock and proving that his threat to use the Satan Bug should be taken seriously. He takes Cavell's wife, Mary, hostage and sets off to London to blackmail the British government by threatening to release the "Satan Bug" in the City of London's financial district. The villain uses his hostage to capture Cavell and several police officers and attempts to kill them with botulinum toxin. Cavell escapes, though one constable is poisoned and dies rapidly. (For dramatic purposes this is from convulsions like nerve agent or strychnine poisoning, rather than the slower paralysis and respiratory failure usually associated with botulism.)
Incapacitating agent
By 1958 a search of the Tropics for venomous animal species in order to isolate and synthesize their toxins was prioritized. For example, snake venoms were studied and The College of Medical Evangelists was under contract to isolate puffer fish poison. The New England Institute for Medical Research and Fort Detrick were studying the properties and biological activity of the Botulinum toxin molecule. The U.S. Army Chemical Warfare Laboratories were isolating shellfish toxin and trying to obtain its structure.
Picrotoxin
Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison). A mixture of two different compounds, picrotoxin occurs naturally in the fruit of the "Anamirta cocculus" plant, although it can also be synthesized chemically.
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.
KCNB1
Potassium delayed rectifiers have been implicated in many pharmacological uses in the investigation of biological toxins for drug development. A main component to many of the toxins with negative effects on delayed rectifiers contain cystine inhibitors that are arranged around disulfide bond formations. Many of these toxins originate from species of tarantulas. "G. spatulata" produces the hanatoxin, which was the first drug to be manipulated to interact with KCNB1 receptors by inhibiting the activation of most potassium voltage-gated channels. Other toxins, such as stromatoxin, heteroscordratoxin, and guangxitoxin, target the selectivity of voltage KCNB1 rectifiers, by either lowering potassium binding affinity or increasing the binding rate of potassium. This can lead to excitotoxicity, or overstimulation of postsynaptic neurons. In nature, the prey of tarantula that are injected with these endogenous toxins induces this excitotoxic effect, producing paralysis for easy capture. Physiologically, these venoms work on KCNB1 rectifier affinity by altering the channels’ voltage sensor, making it more or less sensitive to extracellular potassium concentrations. KCNB1 is also susceptible to tetraethylammonium (TEA) and 4-aminopyridine (4-AP), which completely block all channel activity. TEA also works on calcium-activated potassium channels, furthering its inhibitory effects on neurons and skeletal muscle. Some isoforms of TEA are beneficial for patients with severe Alzheimer’s, as blocking KCNB1 channels reduces the amount of neuronal apoptosis, thereby slowing the rate of dementia. This has been attributed to the oxidative properties of the channel by ROS.
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
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
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.
Pierre Paul Émile Roux
Also in 1883, Roux published, with Alexandre Yersin, the first of his classical works on the causation of diphtheria by the Klebs-Loeffler bacillus, then an extremely prevalent and lethal disease, particularly among children. He studied its toxin and its properties, and began in 1891 to develop an effective serum to treat the disease, following the demonstration, by Emil Adolf von Behring (1854–1917) and Kitasato Shibasaburō (1852–1931) that antibodies against the diphtheric toxin could be produced in animals. He successfully demonstrated the use of this antitoxin with Auguste Chaillou in a study with 300 diseased children in the Hôpital des Enfants-Malades and was henceforth hailed as a scientific hero in medical congresses throughout Europe.
Strychnine
Strychnine was first discovered by French chemists Joseph Bienaimé Caventou and Pierre-Joseph Pelletier in 1818 in the Saint-Ignatius' bean. In some "Strychnos" plants a 9,10-dimethoxy derivative of strychnine, the alkaloid brucine, is also present. Brucine is not as poisonous as strychnine. Historic records indicate that preparations containing strychnine (presumably) had been used to kill dogs, cats, and birds in Europe as far back as 1640. The structure of strychnine was first determined in 1946 by Sir Robert Robinson and in 1954 this alkaloid was synthesized in a laboratory by Robert B. Woodward. This is one of the most famous syntheses in the history of organic chemistry. Both chemists won the Nobel prize (Robinson in 1947 and Woodward in 1965).