(Redirected from Botox)
Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.[1] It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis.[2] Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
Botulinum toxin A
IM (approved), SC, intradermal, into glands
M03AX01 (WHO)
93384-43-1 N
DrugBank
DB00083 N
ECHA InfoCard
C6760H10447N1743O2010S32
149 kg/mol (149,321g/mol) g·mol−1
N Y (what is this?) (verify)
Bontoxilysin
IntEnz
IntEnz view
BRENDA entry
ExPASy
NiceZyme view
KEGG entry
MetaCyc
PDB structures
RCSB PDB PDBe PDBsum
AmiGO / QuickGO
Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD50) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.[3][clarification needed]
There are eight types of botulinum toxin, named type A–H. Types A and B are capable of causing disease in humans, and are also used commercially and medically.[4] Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals.[5] Type H is considered the deadliest substance in the world – an injection of only 2 ng can cause death to an adult.[6] Botulinum toxin types A and B are used in medicine to treat various muscle spasms and diseases characterized by overactive muscle. Commercial forms are marketed under the brand names Botox and Jeuveau, Xeominamong others.[7][8]
Medical usesEdit
Botulinum toxin is used to treat a number of problems.
Muscle spasticityEdit
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,[9] eyelid,[10] vagina,[11] limbs, jaw, and vocal cords.[12] Similarly, botulinum toxin is used to relax clenching of muscles, including those of the oesophagus,[13] jaw,[14] lower urinary tract and bladder,[15] or clenching of the anus which can exacerbate anal fissure.[16] It may also be used for improper eye alignment.[17] Botulinum toxin appears to be effective for refractory overactive bladder.[18]
Other muscle disordersEdit
Strabismus is caused by imbalances in the actions of muscles that rotate the eyes, and can sometimes be relieved by weakening a muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so it might seem that injection would then need to be repeated. However, muscles adapt to the lengths at which they are chronically held,[19] so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect. If there is good binocular vision, the brain mechanism of motor fusion, which aligns the eyes on a target visible to both, can stabilize the corrected alignment.
In January 2014, botulinum toxin was approved by UK's Medicines and Healthcare Products Regulatory Agency (MHRA) for treatment of restricted ankle motion due to lower limb spasticity associated with stroke in adults.[20]
On July 29, 2016, Food and Drug Administration (FDA), of the United States of America approved abobotulinumtoxinA for injection for the treatment of lower limb spasticity in pediatric patients two years of age and older.[21] AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the United States of America, the FDA approves the text of the labels of prescription medicines. The FDA approves which medical conditions the drug manufacturer may sell the drug for. However, those approved by the FDA to prescribe these drugs may freely prescribe them for any condition they wish, called off-label use. Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.[22]
Excessive sweatingEdit
Khalaf Bushara and David Park were the first to demonstrate a nonmuscular use of BTX-A while treating patients with hemifacial spasm in England in 1993, showing that botulinum toxin injections inhibit sweating, and so are useful in treating hyperhidrosis (excessive sweating).[23] BTX-A has since been approved for the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating of unknown cause), which cannot be managed by topical agents.[12][24]
MigraineEdit
In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache.[25]
CosmeticsEdit
Botulinum toxin injected in human face
In cosmetic applications, botulinum toxin (in this context also known as "botox") is considered safe and effective for reduction of facial wrinkles, especially in the uppermost third of the face.[26] Commercial forms are marketed under the brand names Botox by Allergan and Jeuveau by Evolus. [7] The effects of Botox last two to four months and Jeuveau last three to five months. [26] Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin.[26] Smoothing of wrinkles is usually visible four days after treatment for Botox and two days after treatment for Jeuveau and both maximally visible a week following injection.[26] The treated muscles gradually regain function, and generally return to their former appearance three to four months after treatment.[26] Muscles can be treated repeatedly to maintain the smoothed appearance.[26]
Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,[24] neuropathic pain,[27] and some allergy symptoms.[12] In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain.[28] Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion.[29]
Side effectsEdit
Check the protein content in your brand to rule out any anti body resistance.
While botulinum toxin is generally considered safe in a clinical setting, there can be serious side effects from its use. Most commonly, botulinum toxin can be injected into the wrong muscle group or spread from the injection site, causing paralysis of unintended muscles.
Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and trouble swallowing. Side effects are not limited to direct paralysis however, and can also include headaches, flu-like symptoms, and allergic reactions.[30] Just as cosmetic treatments only last a number of months, paralysis side-effects can have the same durations.[citation needed] At least in some cases, these effects are reported to dissipate in the weeks after treatment.[citation needed] Bruising at the site of injection is not a side effect of the toxin but rather of the mode of administration, and is reported as preventable if the clinician applies pressure to the injection site; when it occurs, it is reported in specific cases to last 7–11 days.[citation needed] When injecting the masseter muscle of the jaw, loss of muscle function can result in a loss or reduction of power to chew solid foods.[30]
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.[30] 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.[30]
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.[31] 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.[32] 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.[32] In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each.[33] A similar warning was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.[34]
Role in diseaseEdit
Main article: Botulism
Botulinum toxin produced by Clostridium botulinum is the cause of botulism.[10] Humans most commonly ingest the toxin from eating improperly-canned foods in which C. botulinum has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome.[35] In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.[1] 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.[36] For wound infections, infected material may be removed surgically.[36] 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.[36] The nerve damage heals over time, generally over weeks to months.[5] With proper treatment, the case fatality rate for botulinum poisoning can be greatly reduced.[36]
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, except for strain H.[37]
Mechanism of actionEdit
Target molecules of botulinum neurotoxin (abbreviated BoNT) and tetanus neurotoxin (TeNT), toxins acting inside the axon terminal.[38]
Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to nerves which use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis.[39] As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin which triggers it to push across the vesicle membrane and into the cell cytoplasm.[1] Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles can’t bind to the intracellular cell membrane,[39] preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to paralysis.[1]
The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases.[12] The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide.[40] The heavy chain contains domains with several functions: it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies.[1][40] The light chain is a zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family which is responsible for fusion. The cleaved SNAP-25 is unable to mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings.[1] This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.[1]
The seven toxin types (A–G) have different tertiary structures and sequence differences.[40][41] While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members.[38] 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).[40]
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”.[42] 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.[43] His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.[44]
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,[45] which was later purified by P Tessmer Snipe and Hermann Sommer.[46]
Food canningEdit
Find sources: "Botulinum toxin" – news · newspapers · books · scholar · JSTOR (August 2018) (Learn how and when to remove this template message)
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.
World War IIEdit
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff[47] 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.
The mechanism of botulinum toxin action – blocking the release from nerve endings of the neurotransmitter acetylcholine – was elucidated in the mid-1900s,[48] and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues.
StrabismusEdit
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.[49] 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,[50] Alan B. Scott and colleagues injected botulinum toxin into monkey extraocular muscles.[51] The result was remarkable: a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side-effects.
After working out techniques for freeze-drying, buffering with albumin, and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility in 1980,[52] and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner").
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.[53]
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.[54] This was under the 1983 US Orphan Drug Act.[55]
Richard Clark, a plastic surgeon from Sacramento (CA), was the first to document a cosmetic use for botulinum toxin.[56] He treated forehead asymmetry caused by left sided forehead nerve paralysis that occurred during a cosmetic facelift. Since the injured nerve could possibly regenerate by 24 months, a two-year waiting period was necessary before definitive surgical treatment could be done. Clark realized that botulinum toxin, which had been previously used only for cross eyed babies and facial tics, could also be injected to smooth the wrinkles of the right forehead to match her paralyzed left. He received FDA approval for this cosmetic application of the toxin and successfully treated the person and published the case study in 1989.[56]
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.[57] Brin, and a group at Columbia University under Monte Keen made similar reports.[58] In 2002, following clinical trials, the FDA approved Botox Cosmetic, botulinum A toxin to temporarily improve the appearance of moderate-to-severe glabellar lines.[59] 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.[60][61]
Chronic painEdit
William J. Binder reported in 2000 that patients who had cosmetic injections around the face reported relief from chronic headache.[62] 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.[63][64]
Society and cultureEdit
EconomicsEdit
This article needs to be updated. Please update this article to reflect recent events or newly available information. (October 2017)
As of 2018, botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the American Society of Plastic Surgeons[65]. 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.
The global market for botulinum toxin products, driven by their cosmetic applications, is forecast to reach $2.9 billion by 2018. The facial aesthetics market, of which they are a component, is forecast to reach $4.7 billion ($2 billion in the U.S.) in the same timeframe.[66]
BioterrorismEdit
Botulinum toxin has been recognized as a potential agent for use in bioterrorism.[67] It can be absorbed through the eyes, mucous membranes, respiratory tract, and through non-intact skin.[68]
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.[citation needed] Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.[citation needed]
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.[citation needed] 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 LD50 units per milliliter have been detected in poisoned patients.[69]
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.[70]
During the early 1980s, the 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. Their reports were later found to be incorrect; no such lab was ever found.[71]
Brand namesEdit
The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (April 2017) (Learn how and when to remove this template message)
Botulinum toxin A is marketed under the brand names Jeuveau, Botox and Xeomin. Botulinum toxin B is marketed under the brand name Myobloc.
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.[72] 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.[33]
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.[73] Lanzhou Institute of Biological Products in China manufactures a BTX-A product; as of 2014 it was the only BTX-A approved in China.[73] BTX-A is also sold as Lantox and Prosigne on the global market.[74] Neuronox, a BTX-A product, was introduced by Medy-Tox Inc. of South Korea in 2009;[75]
Toxin productionEdit
Botulism toxins are produced by bacteria of the genus Clostridium, namely Clostridium botulinum, C. butyricum, C. baratii and C. argentinense,[76] which are widely distributed, including in soil and dust. As well, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning.[citation needed] Some food products such as honey can contain amounts of the bacteria.[citation needed]
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.[citation needed] Critically, it is ingestion of toxin rather than spores or vegetative bacteria that causes botulism.[citation needed] Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, and so is preventable.[citation needed] Infant botulism cases arise chiefly as a result of environmental exposure and are therefore more difficult to prevent.[citation needed] Infant botulism arising from consumption of honey can be prevented by eliminating honey from diets of children less than 12 months old.[77]
Organism and toxin susceptibilitiesEdit
This section needs expansion with: modern content and referencing on antibiotic susceptibilities. You can help by adding to it. (February 2015)
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.[5] The toxin itself is rapidly destroyed by heat, such as in thorough cooking.[78] The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time.[79]
The botulinum toxin is denatured and thus deactivated at temperatures greater than 80 °C (176 °F).[80] As a zinc metalloprotease (see below), the toxin's activity is also susceptible, post-exposure, to inhibition by protease inhibitors, e.g., zinc-coordinating hydroxamates.[40][81]
ResearchEdit
Blepharospasm and strabismusEdit
See also: Botulinum toxin therapy of strabismus
University-based ophthalmologists in the US and Canada further refined the use of botulinum toxin as a therapeutic agent. By 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of blepharospasm and strabismus.[82] Side effects in treatment of this condition were deemed to be rare, mild and treatable.[83] The beneficial effects of the injection lasted only 4–6 months. Thus, blepharospasm patients required re-injection two or three times a year.
In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug because of an inability to obtain product liability insurance. Patients became desperate, as supplies of Botox were gradually consumed, forcing him to abandon patients who would have been due for their next injection. For a period of four months, American blepharospasm patients had to arrange to have their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.[53]
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.[54]
Botox has not been approved for any pediatric use.[33] 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.[33] In the case of treatment of infantile esotropia in patients younger than 12 years of age, several studies have yielded differing results.[22][better source needed]
CosmeticEdit
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.[56] 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.[57] Similar effects had reportedly been observed by a number of independent groups (Brin, and the Columbia University group under Monte Keen.[58]) 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).[59] Subsequently, cosmetic use of botulinum toxin type A has become widespread.[84] The results of Botox Cosmetic can last up to four months and may vary with each patient.[85] 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.[60][61]
BTX-A has also been used in the treatment of gummy smiles,[86][87] 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.[88] 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).[89][90]
Upper motor neuron syndromeEdit
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.[20] 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.
SweatingEdit
Cervical dystoniaEdit
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.[73]
Chronic migraineEdit
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.[91][92]
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[93] 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.[94]
DepressionEdit
See also: List of investigational antidepressants
A few small trials have found benefits in people with depression.[95][96] Research is based on the facial feedback hypothesis.[97]
Premature ejaculationEdit
See also: List of investigational sexual dysfunction drugs
The drug is under development for the treatment of premature ejaculation.[96]
Microbial toxins
^ a b c d e f g Montecucco C, Molgó J (June 2005). "Botulinal neurotoxins: revival of an old killer". Current Opinion in Pharmacology. 5 (3): 274–79. doi:10.1016/j.coph.2004.12.006. PMID 15907915.
^ Figgitt, David P.; Noble, Stuart (2002). "Botulinum Toxin B". Drugs. 62 (4): 705–722. doi:10.2165/00003495-200262040-00011. PMID 11893235.
^ Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K (February 2001). "Botulinum toxin as a biological weapon: medical and public health management". JAMA. 285 (8): 1059–70. doi:10.1001/jama.285.8.1059. PMID 11209178.
^ American Society of Health-System Pharmacists (October 27, 2011). "Botulinum Toxin Type A". drugs.com. Retrieved 4 March 2015.
^ a b c "Fact Sheet: Botulism". World Health Organization. Retrieved 4 October 2016.
^ Weller C (15 October 2013). "New Botulinum Toxin Deemed Deadliest Substance Ever: Sniffing 13-Billionths of a Gram Can Kill". Medical Daily.
^ a b KRAUSE R (10 June 2019). "Jeuveau, The Most Affordable Wrinkle Injectable". refinery29.com.
^ "Actavis plc is now Allergan plc". Allergan. 15 June 2015. Retrieved 16 June 2015.
^ "Cervical dystonia". Mayo Clinic. 2014-01-28. Retrieved 2015-10-14.
^ a b Shukla HD, Sharma SK (2005). "Clostridium botulinum: a bug with beauty and weapon". Critical Reviews in Microbiology. 31 (1): 11–18. doi:10.1080/10408410590912952. PMID 15839401.
^ Pacik PT (December 2009). "Botox treatment for vaginismus". Plastic and Reconstructive Surgery. 124 (6): 455e–56e. doi:10.1097/PRS.0b013e3181bf7f11. PMID 19952618.
^ a b c d e Felber ES (October 2006). "Botulinum toxin in primary care medicine". The Journal of the American Osteopathic Association. 106 (10): 609–14. PMID 17122031.
^ Stavropoulos SN, Friedel D, Modayil R, Iqbal S, Grendell JH (March 2013). "Endoscopic approaches to treatment of achalasia". Therapeutic Advances in Gastroenterology. 6 (2): 115–35. doi:10.1177/1756283X12468039. PMC 3589133. PMID 23503707.
^ Long H, Liao Z, Wang Y, Liao L, Lai W (February 2012). "Efficacy of botulinum toxins on bruxism: an evidence-based review". International Dental Journal. 62 (1): 1–5. doi:10.1111/j.1875-595X.2011.00085.x. PMID 22251031.
^ Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, Gravas S, Madersbacher S (October 2011). "Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)". European Urology. 60 (4): 784–95. doi:10.1016/j.eururo.2011.07.001. PMID 21782318.
^ Trzciński R, Dziki A, Tchórzewski M (2002). "Injections of botulinum A toxin for the treatment of anal fissures". The European Journal of Surgery = Acta Chirurgica. 168 (12): 720–23. doi:10.1080/11024150201680030. PMID 15362583.
^ Kowal L, Wong E, Yahalom C (December 2007). "Botulinum toxin in the treatment of strabismus. A review of its use and effects". Disability and Rehabilitation. 29 (23): 1823–31. doi:10.1080/09638280701568189. PMID 18033607.
^ Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D (December 2011). "Botulinum toxin injections for adults with overactive bladder syndrome". The Cochrane Database of Systematic Reviews (12): CD005493. doi:10.1002/14651858.CD005493.pub3. PMID 22161392.
^ Scott AB (1994). "Change of eye muscle sarcomeres according to eye position". Journal of Pediatric Ophthalmology and Strabismus. 31 (2): 85–88. PMID 8014792.
^ a b UK Approves New Botox Use Archived 2014-02-22 at the Wayback Machine. dddmag.com. February 4, 2014
^ "FDA Approved Drug Products – Dysport". www.accessdata.fda.gov. U.S. Food and Drug Administration. Retrieved 2016-11-07.
^ a b Ocampo VV, Foster CS (May 30, 2012). "Infantile Esotropia Treatment & Management". Medscape. Retrieved April 6, 2014.
^ a b Bushara KO, Park DM (November 1994). "Botulinum toxin and sweating". Journal of Neurology, Neurosurgery, and Psychiatry. 57 (11): 1437–38. doi:10.1136/jnnp.57.11.1437. PMC 1073208. PMID 7964832.
^ a b c Eisenach JH, Atkinson JL, Fealey RD (May 2005). "Hyperhidrosis: evolving therapies for a well-established phenomenon". Mayo Clinic Proceedings. 80 (5): 657–66. doi:10.4065/80.5.657. PMID 15887434.
^ "FDA Approves Botox to Treat Chronic Migraines". WebMD. Retrieved 12 May 2017.
^ a b c d e f Small R (August 2014). "Botulinum toxin injection for facial wrinkles". American Family Physician. 90 (3): 168–75. PMID 25077722.
^ Mittal SO, Safarpour D, Jabbari B (February 2016). "Botulinum Toxin Treatment of Neuropathic Pain". Seminars in Neurology. 36 (1): 73–83. doi:10.1055/s-0036-1571953. PMID 26866499.
^ Charles PD (November 2004). "Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses". American Journal of Health-System Pharmacy. 61 (22 Suppl 6): S11–23. doi:10.1093/ajhp/61.suppl_6.S11. PMID 15598005.
^ Singh, Jasvinder A; Fitzgerald, Patrick M (2010-09-08). "Botulinum toxin for shoulder pain". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd008271.pub2. ISSN 1465-1858.
^ a b c d Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM (September 2005). "Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases". Journal of the American Academy of Dermatology. 53 (3): 407–15. doi:10.1016/j.jaad.2005.06.011. PMID 16112345.
^ "FDA Notifies Public of Adverse Reactions Linked to Botox Use". Fda.gov. 8 February 2008. Retrieved May 6, 2012.
^ a b "FDA Gives Update on Botulinum Toxin Safety Warnings; Established Names of Drugs Changed". FDA Press Announcement. August 3, 2009. Retrieved 21 September 2016.
^ a b c d "Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc)". fda.gov. Food and Drug Administration. Retrieved 1 September 2015.
^ "Botox chemical may spread, Health Canada confirms". CBC News. January 13, 2009. Archived from the original on 21 February 2009.
^ "Kinds of Botulism". Centers for Disease Control and Prevention. Retrieved 4 October 2016.
^ a b c d "Botulism – Diagnosis and Treatment". Centers for Disease Control and Prevention. Retrieved 5 October 2016.
^ Arnon, Stephen S.; Barash, Jason R. (2014-01-15). "A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins". The Journal of Infectious Diseases. 209 (2): 183–191. doi:10.1093/infdis/jit449. ISSN 0022-1899. PMID 24106296.
^ a b Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, McWilliams LG, Schmidt JG, Martinez RA, Ashley DL (October 2005). "Botulinum neurotoxin detection and differentiation by mass spectrometry". Emerging Infectious Diseases. 11 (10): 1578–83. doi:10.3201/eid1110.041279. PMC 3366733. PMID 16318699.
^ a b Dressler, D; Saberi, FA; Barbosa, ER (March 2005). "Botulinum toxin: mechanisms of action". Arquivos de Neuro-Psiquiatria. 63 (1): 180–85. doi:10.1159/000083259. PMID 15830090.
^ a b c d e Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL (December 2010). "Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication". Molecules. 16 (1): 202–20. doi:10.3390/molecules16010202. PMC 6259422. PMID 21193845.
^ Hill KK, Smith TJ (2013). "Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes". In Rummel A, Binz T (eds.). Botulinum neurotoxins. Current Topics in Microbiology and Immunology. 364. Heidelberg: Springer. pp. 1–20. doi:10.1007/978-3-642-33570-9_1. ISBN 978-3-642-33569-3. PMID 23239346.
^ Kerner J (1820). Neue Beobachtungen über die in Württemberg so häufig vorfallenden tödlichen Vergiftungen durch den Genuss geräucherter Würste. Tübingen: Osiander.
^ Kerner J (1822). Das Fettgift oder die Fettsäure und ihre Wirkungen auf den thierischen Organismus, ein Beytrag zur Untersuchung des in verdorbenen Würsten giftig wirkenden Stoffes. Stuttgart, Tübingen: Cotta. pp. 681–87. OCLC 863571562.
^ Erbguth FJ, Naumann M (November 1999). "Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the "sausage poison"". Neurology. 53 (8): 1850–53. doi:10.1212/wnl.53.8.1850. PMID 10563638.
^ van Ermengem E (1979). "Classics in infectious diseases. A new anaerobic bacillus and its relation to botulism. E. van Ermengem. Originally published as "Ueber einen neuen anaëroben Bacillus und seine Beziehungen zum Botulismus" in Zeitschrift für Hygiene und Infektionskrankheiten 26: 1–56, 1897". Reviews of Infectious Diseases (in German). 1 (4): 701–19. PMID 399378. Original doi:10.1007/BF02220526
^ Snipe PT, Sommer H (August 1928). "Studies on Botulinus Toxin: 3. Acid Precipitation of Botulinus Toxin". The Journal of Infectious Diseases. 43 (2): 152–60. doi:10.1093/infdis/43.2.152. JSTOR 30083772.
^ Lamanna C, McElroy OE, Eklund HW (May 1946). "The purification and crystallization of Clostridium botulinum type A toxin". Science. 103 (2681): 613–14. Bibcode:1946Sci...103..613L. doi:10.1126/science.103.2681.613. PMID 21026141.
^ Burgen AS, Dickens F, Zatman LJ (August 1949). "The action of botulinum toxin on the neuro-muscular junction". The Journal of Physiology. 109 (1–2): 10–24. doi:10.1113/jphysiol.1949.sp004364. PMC 1392572. PMID 15394302.
^ Magoon E, Cruciger M, Scott AB, Jampolsky A (May 1982). "Diagnostic injection of Xylocaine into extraocular muscles". Ophthalmology. 89 (5): 489–91. doi:10.1016/s0161-6420(82)34764-8. PMID 7099568.
^ Drachman DB (August 1964). "Atrophy of skeletal muscle in chick embryos treated with botulinum toxin". Science. 145 (3633): 719–21. Bibcode:1964Sci...145..719D. doi:10.1126/science.145.3633.719. PMID 14163805.
^ Scott AB, Rosenbaum A, Collins CC (December 1973). "Pharmacologic weakening of extraocular muscles". Investigative Ophthalmology. 12 (12): 924–27. PMID 4203467.
^ Scott AB (October 1980). "Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery". Ophthalmology. 87 (10): 1044–49. doi:10.1016/s0161-6420(80)35127-0. PMID 7243198.
^ a b Boffey, Philip M. (October 14, 1986). "Loss Of Drug Relegates Many To Blindness Again". The New York Times. Retrieved July 14, 2010.
^ a b United States Department of Health and Human Services (April 30, 2009). "Re: Docket No. FDA-2008-P-0061" (PDF). Food and Drug Administration. Retrieved July 26, 2010.
^ Wellman-Labadie O, Zhou Y (May 2010). "The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?". Health Policy. 95 (2–3): 216–28. doi:10.1016/j.healthpol.2009.12.001. PMID 20036435.
^ a b c Clark RP, Berris CE (August 1989). "Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis". Plastic and Reconstructive Surgery. 84 (2): 353–55. doi:10.1097/01.prs.0000205566.47797.8d. PMID 2748749.
^ a b Carruthers JD, Carruthers JA (January 1992). "Treatment of glabellar frown lines with C. botulinum-A exotoxin". The Journal of Dermatologic Surgery and Oncology. 18 (1): 17–21. doi:10.1111/j.1524-4725.1992.tb03295.x. PMID 1740562.
^ a b Keen M, Kopelman JE, Aviv JE, Binder W, Brin M, Blitzer A (April 1994). "Botulinum toxin A: a novel method to remove periorbital wrinkles". Facial Plastic Surgery. 10 (2): 141–46. doi:10.1055/s-2008-1064563. PMID 7995530.
^ a b "Botulinum Toxin Type A Product Approval Information – Licensing Action 4/12/02". Food and Drug Administration. October 29, 2009. Retrieved July 26, 2010.
^ a b "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Assay for BOTOX and BOTOX Cosmetic (onabotulinumtoxinA)". Allergan. June 24, 2011. Archived from the original on June 26, 2011. Retrieved June 26, 2011.
^ a b "In U.S., Few Alternatives To Testing On Animals". Washington Post. April 12, 2008. Retrieved June 26, 2011.
^ Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM (December 2000). "Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study". Otolaryngology–Head and Neck Surgery. 123 (6): 669–76. doi:10.1067/mhn.2000.110960. PMID 11112955.
^ Jackson JL, Kuriyama A, Hayashino Y (April 2012). "Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis". JAMA. 307 (16): 1736–45. doi:10.1001/jama.2012.505. PMID 22535858.
^ Ramachandran R, Yaksh TL (September 2014). "Therapeutic use of botulinum toxin in migraine: mechanisms of action". British Journal of Pharmacology. 171 (18): 4177–92. doi:10.1111/bph.12763. PMC 4241086. PMID 24819339.
^ "New plastic surgery statistics reveal trends toward body enhancement". Plastic Surgery. 2019-03-11. Archived from the original on 2019-03-12.
^ Chapman, Paul (May 10, 2012). "The global botox market forecast to reach $2.9 billion by 2018". Archived from the original on 2012-08-06. Retrieved October 5, 2012.
^ Koirala J, Basnet S (July 14, 2004). "Botulism, Botulinum Toxin, and Bioterrorism: Review and Update". Medscape. Cliggott Publishing. Retrieved July 14, 2010.
^ Clostridium botulinum – Public Health Agency of Canada. Phac-aspc.gc.ca (April 19, 2011). Retrieved on May 6, 2012.
^ Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Ca.: Biomedical Publications. pp. 260–61. ISBN 978-0-9626523-9-4.
^ http://www.emsworld.com/article/10324792/botulinum-toxin-a-bioterrorism-weapon
^ McAdams D, Kornblet S (2011). "Baader-Meinhof Group (OR Baader-Meinhof Gang". In Pilch RF, Zilinskas RA (eds.). Encyclopedia of Bioterrorism Defense. Wiley-Liss. doi:10.1002/0471686786.ebd0012.pub2. ISBN 978-0-471-68678-1.
^ "2011 Allergan Annual Report" (PDF). Allergan. Retrieved May 3, 2012. See PDF p. 7.
^ a b c Walker TJ, Dayan SH (February 2014). "Comparison and overview of currently available neurotoxins". The Journal of Clinical and Aesthetic Dermatology. 7 (2): 31–39. PMC 3935649. PMID 24587850.
^ "Botulinum Toxin Type A". Hugh Source (International) Limited. Retrieved July 14, 2010.
^ Petrou I (Spring 2009). "Medy-Tox Introduces Neuronox to the Botulinum Toxin Arena" (PDF). The European Aesthetic Guide. Archived from the original (PDF) on 2013-03-20. Retrieved 2009-12-09.
^ Schantz EJ, Johnson EA (March 1992). "Properties and use of botulinum toxin and other microbial neurotoxins in medicine". Microbiological Reviews. 56 (1): 80–99. PMC 372855. PMID 1579114.
^ Botulism, General Information – NCZVED. Cdc.gov. Retrieved on May 6, 2012.
^ Licciardello JJ, Nickerson JT, Ribich CA, Goldblith SA (March 1967). "Thermal inactivation of type E botulinum toxin". Applied Microbiology. 15 (2): 249–56. PMC 546888. PMID 5339838.
^ Setlow P (April 2007). "I will survive: DNA protection in bacterial spores". Trends in Microbiology. 15 (4): 172–80. doi:10.1016/j.tim.2007.02.004. PMID 17336071.
^ Jay JM, Loessner MJ, Golden DA (2005). "Chapter 24: Food Poisoning Caused by Gram-Positive Sporeforming Bacteria". Modern Food Microbiology: Seventh Edition. New York: Springer. p. 581. ISBN 978-0-387-23180-8.
^ Capková K, Salzameda NT, Janda KD (October 2009). "Investigations into small molecule non-peptidic inhibitors of the botulinum neurotoxins". Toxicon. 54 (5): 575–82. doi:10.1016/j.toxicon.2009.03.016. PMC 2730986. PMID 19327377.
^ Flanders M, Tischler A, Wise J, Williams F, Beneish R, Auger N (June 1987). "Injection of type A botulinum toxin into extraocular muscles for correction of strabismus". Canadian Journal of Ophthalmology. 22 (4): 212–17. PMID 3607594.
^ "Botulinum toxin therapy of eye muscle disorders. Safety and effectiveness. American Academy of Ophthalmology". Ophthalmology. Suppl: 37–41. September 1989. doi:10.1016/s0161-6420(89)32989-7. PMID 2779991.
^ Giesler M (2012). "How Doppelgänger Brand Images Influence the Market Creation Process: Longitudinal Insights from the Rise of Botox Cosmetic". Journal of Marketing. 76 (6): 55–68. doi:10.1509/jm.10.0406.
^ "BOTOX Cosmetic (onabotulinumtoxinA) Product Information". Allergan. January 22, 2014.
^ Nayyar P, Kumar P, Nayyar PV, Singh A (December 2014). "BOTOX: Broadening the Horizon of Dentistry". Journal of Clinical and Diagnostic Research : JCDR. 8 (12): ZE25–29. doi:10.7860/JCDR/2014/11624.5341. PMC 4316364. PMID 25654058.
^ Al-Fouzan AF, Mokeem LS, Al-Saqat RT, Alfalah MA, Alharbi MA, Al-Samary AE (June 2017). "Botulinum Toxin for the Treatment of Gummv Smile". The Journal of Contemporary Dental Practice. 18 (6): 474–78. doi:10.5005/jp-journals-10024-2068. PMID 28621277.
^ Hwang WS, Hur MS, Hu KS, Song WC, Koh KS, Baik HS, Kim ST, Kim HJ, Lee KJ (January 2009). "Surface anatomy of the lip elevator muscles for the treatment of gummy smile using botulinum toxin". The Angle Orthodontist. 79 (1): 70–77. doi:10.2319/091407-437.1. PMID 19123705.
^ Gracco A, Tracey S (May 2010). "Botox and the gummy smile". Progress in Orthodontics. 11 (1): 76–82. doi:10.1016/j.pio.2010.04.004. PMID 20529632.
^ Mazzuco R, Hexsel D (December 2010). "Gummy smile and botulinum toxin: a new approach based on the gingival exposure area". Journal of the American Academy of Dermatology. 63 (6): 1042–51. doi:10.1016/j.jaad.2010.02.053. PMID 21093661.
^ Walsh S (October 15, 2010). "FDA approves Botox to treat chronic migraine". FDA Press Releases. Retrieved October 15, 2010.
^ Watkins T (October 15, 2010). "FDA approves Botox as migraine preventative". CNN (US).
^ Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, Diener HC, Brin MF (June 2010). "OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program". Headache. 50 (6): 921–36. doi:10.1111/j.1526-4610.2010.01678.x. PMID 20487038.
^ Ashkenazi A (March 2010). "Botulinum toxin type a for chronic migraine". Current Neurology and Neuroscience Reports. 10 (2): 140–46. doi:10.1007/s11910-010-0087-5. PMID 20425239.
^ Magid M, Keeling BH, Reichenberg JS (November 2015). "Neurotoxins: Expanding Uses of Neuromodulators in Medicine – Major Depressive Disorder". Plastic and Reconstructive Surgery. 136 (5 Suppl): 111S–19S. doi:10.1097/PRS.0000000000001733. PMID 26441090.
^ a b "Onabotulinum toxin A - Allergan - AdisInsight".
^ Finzi E, Rosenthal NE (May 2014). "Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial". Journal of Psychiatric Research. 52: 1–6. doi:10.1016/j.jpsychires.2013.11.006. PMID 24345483.
A Poison That Can Heal from the U.S. Food and Drug Administration
BotDB: extensive resources on BoNT structures, inhibitors, kinetics, and literature
A consumer sociological investigation of Botox Cosmetic's Rise
Retrieved from "https://en.wikipedia.org/w/index.php?title=Botulinum_toxin&oldid=905905451"


Timeline by theme
Arts, Culture and Identity
Historical Figures and Acadians
Acadians
This timeline highlights events and people related to Acadian History.
Champlain's First Trip
Samuel de Champlain boarded the Bonne-Renommée at Honfleur, France, destined for New France, as a private passenger on Gravé Du Pont's expedition.
Champlain Arrives at Gaspé
Samuel de Champlain arrived at Gaspé, where he first heard about Acadia.
Arts, Culture and Identity Politics and Society
Founding of the Ordre de Bon Temps
Ordre de Bon Temps ("Order of Good Cheer"), was founded at Port-Royal by Samuel de Champlain to maintain spirits and pass the time. Members took turns providing fresh game and, as chief steward of the day, leading a ceremonial procession to the table.
Expedition to Massachusetts
Samuel de Champlain and Jean de Poutrincourt launched another expedition from Port-Royal to explore the coast of Massachusetts, hoping to establish friendly relationships with the Secoudon and Messamouet in the area. Their efforts were met with hostility and soon abandoned.
Marc Lescarbot's Theatre
Marc Lescarbot put on the first European theatrical production in Canada, or North America, called Le Théâtre de Neptune.
Port-Royal Abandoned
The Port-Royal settlement was abandoned on orders from France. On Sept 3, after skirting the Straits of Canso and mapping the Atlantic coastline from Cape Breton to the south of Cap Blanc, Samuel de Champlain and the other voyagers headed home to St Malo. Only Poutrincourt would return, in 1610.
First Black Person in Canada
The first Black person thought to have set foot on Canadian soil was Mathieu Da Costa, a free man who was hired by Europeans to act as a translator.
de Monts's Monopoly Renewed
Henri IV of France renewed de Monts's fur-trade monopoly, temporarily saving the colony at Port-Royal.
Champlain Leaves on 3rd Voyage
As lieutenant to the Sieur de Monts, Samuel de Champlain set out on his third voyage to New France. He arrived at Tadoussac on 3 June.
First Jesuits Arrive in New France
The first Jesuits to arrive in New France, Pierre Biard and Ennemond Massé, arrived at Port-Royal on May 22, 1611.
Champlain Becomes Governor
Louis XIII wrote to Samuel de Champlain, commissioning him to govern New France and to do so in accordance with the laws and customs of France. From that point, Champlain devoted himself almost exclusively to administration and his career as an explorer ended.
Treaty of Saint-Germain-en-Laye
France recovered Québec from England in the Treaty of Saint-Germain, along with compensation for goods siezed when Champlain surrendered Québec.
Historical Figures and Acadians Politics and Society
Isaac de Razilly becomes governor of Acadia
Isaac de Razilly was selected to lead an expedition to re-establish the colony of Acadia after three years of Scottish occupation. With his headquarters at La Hève and an establishment of some 300 soldiers and colonists, Razilly worked effectively to consolidate the French hold on Acadia until his unexpected death in 1635.
Champlain Recommended to Lead Colony
Asked by Cardinal Richelieu to take command of the colony, Isaac de Razilly deferred to Champlain as being more competent in colonial affairs.
Death of Champlain
Champlain died at Québec. He had suffered a stroke the previous October and signed his will November 17.
Attack on Fort La Tour
D'Aulnay de Charnisay attacked Fort La Tour. La Tour's wife surrendered on the understanding that the garrison would be spared but Charnisay executed all the men but one, who had agreed to be executioner.
Birth of Sir William Phips
Sir William Phips, adventurer, was born near Kennebec, Maine.
La Tour Made Governor
Charles de La Tour was made governor of Acadia.
Sedgwick Captures Port-Royal
Robert Sedgwick, commander-in-chief of the New England coast, captured Port-Royal.
Birth of Daniel de Subercase
Daniel d'Auger de Subercase, last governor of French Acadia, was born at Orthez, France.
Treaty of Breda
The Treaty of Breda provided for French restoration of the English part of the island of St Christopher's, West Indies, in exchange for Acadia, captured from the French in 1654.
Phips Plunders Port-Royal
Sir William Phips captured and plundered Port-Royal.
Treaty of Ryswick
The Treaty of Ryswick between England and France provided for the restoration of all Hudson's Bay Co posts seized by Pierre le Moyne d'Iberville.
England Declares War on France
England declared war on France, beginning the War of the Spanish Succession; it lasted until 1713.
Nicholson Captures Port-Royal
Francis Nicholson and an English force of 2000 men captured Port-Royal.
Treaty of Utrecht Signed
The Treaty of Utrecht was signed, ending the War of the Spanish Succession. It recognized the claim of the Hudson's Bay Co to Rupert's Land, and Acadia became a permanent English possession.
Contract for Construction of Louisbourg
A contract was signed for the building of the King’s Bastion and citadel barracks of Louisbourg. Contractor Michel-Philippe Isabeau became known for his speedy work but also for his poor bookkeeping, exploitation of contract loopholes and habit of paying workers in goods (especially liquor). Isabeau died in 1724, and the work was carried on by others for another 20 years before the great fortress was finally complete.
War of the Austrian Succession
Britain declared war on Spain, opening the hostilities that led to the War of the Austrian Succession, called King George's War in the colonies.
Louisbourg Surrenders
The fortress of Louisbourg surrendered to the English.
Ramezay's Attack on Grand Pré
Claude de Ramezay, guided by Acadians, attacked the British position at Grand Pré.
Treaty of Aix-la-Chapelle
The Treaty of Aix-la-Chapelle ended the War of the Austrian Succession. PEI, Cape Breton Island and Louisbourg were returned to France.
Expulsion of the Acadians
Acadian delegates who refused the oath of allegiance were dispersed from Minas, and over the next few months most of the Acadian population of Nova Scotia was rounded up and transported away. About one half of the Acadians perished.
The fortress of Louisbourg surrendered for the last time. The French inhabitants were returned to France.
Andrew Rollo Captures Île Saint-Jean
Brigadier-General Andrew Rollo, the 5th Lord Rollo, captured Île Saint-Jean (now Prince Edward Island) from the French at the height of the Seven Years'' War. Roughly 3,500 Acadians were swiftly repatriated to France whilst Rollo constructed Fort Amherst in honour of, and on orders from, General Jeffrey Amherst.
Treaty of Paris 1763
The Treaty of Paris was signed, ending the Seven Years' War. France ceded to Britain all North American possessions except Saint-Pierre and Miquelon off Nfld, and Louisiana (sold in 1803). The treaty authorized freedom of religion in the colony.
Royal Proclamation
The Royal Proclamation was issued by King George III, setting the western boundary of British settlement following the Seven Years War. Historic, foundational, flawed, the Proclamation stated that Aboriginal title had existed and continued to exist. All land was considered Aboriginal land until ceded by treaty, which could only be annexed by the Crown.
New Brunswick Separates
New Brunswick was established as a separate colony from Nova Scotia.
Birth of Edward Barron Chandler
Edward Barron Chandler was born in Amherst, Nova Scotia. Popular in New Brunswick’s political circles, Chandler served in the House of Assembly. A Father of Confederation, he attended the major Confederation conferences, though he did not support Sir John A. Macdonald’s push for centralization.
Aroostook War
New Brunswick and Maine clashed over lumbering in what became known as the Aroostook War (sometimes called the Pork and Beans War), over the undefined border.
Birth of Sir Pierre-Amand Landry
Sir Pierre-Amand Landry, lawyer, politician, judge, first NB Acadian Cabinet minister and Supreme Court judge, and the only knighted Acadian, born at Memramcook, NB.
Publication in Boston of Evangeline, A Tale of Acadia
Evangeline is a narrative poem (1847) by Henry Wadsworth Longfellow inspired by the expulsion of the Acadians in 1755. The poem tells of the love and wanderings of two young Acadians, Évangéline Bellefontaine and Gabriel Lajeunesse, who, the day after their betrothal, were deported from Grand Pré, NS, on different Louisiana-bound ships. The pair are reunited years later in a Philadelphia almshouse where she, now a Sister of Mercy, finds him destitute and dying.
Arts, Culture and Identity Historical Figures and Acadians Politics and Society
Birth of Pascal Poirier
Pascal Poirier, one of the leading figures of the Acadian Renaissance, was born in Shediac, NB. In 1885, he became the first Acadian appointed to the Senate.
Stanislas Poirier (Perry) elected to the PEI Assembly
Stanislas-François Poirier (Perry) became the first Acadian elected to the House of Assembly of Prince Edward Island. Twenty years later, in 1874, he became the first Acadian Member of Parliament.
Birth of Peter John Veniot
Born in Richibucto, NB, Peter John Veniot, "Pierre," is the first Acadian NB premier from 1923 to 1925 (non-elected). He succeeded W.E. Foster as premier in 1923 and supported public ownership of the provincial hydro system and the Maritime Rights Movement. He was recognized as the leader of Acadian Liberalism. Following the defeat of his party in 1925, he ran successfully as MP for Gloucester and was appointed postmaster general by PM King. He sat as an MP until his death in 1936.
Collège Saint-Joseph de Memramcook founded in NB
Father Camille Lefebvre, member of the congregation of the Fathers of Sainte-Croix, founded the Collège Saint-Joseph in Memramcook, New Brunswick. The establishment of this institution was significant because the graduates quickly began to play active roles in the Acadian community and, with the help of the clergy, started questioning their own identity and asserting their aspirations as francophones in an anglophone environment. Collège Saint-Joseph was one of three colleges that merged in 1963 to become the Université de Moncton.
Le Moniteur Acadien founded
The first Acadian newspaper, Le Moniteur Acadien, was founded by Israël Landry in Shediac, New Brunswick. The paper, whose first issue appeared on 8 July 1867, marked the beginning of the Acadian Renaissance.
Birth of Aubin-Edmond Arsenault
Premier of PEI Aubin-Edmond Arsenault was born at Egmont Bay, PEI. Arsenault was the first Acadian premier of any Canadian province.
New Brunswick Schools
The New Brunswick government passed the Common Schools Act to strengthen and reform the school system. At the same time, it abandoned an informal system of separate schools that had grown up since the 1850s.
Stanislas Poirier (Perry) elected to the House of Commons
Stanislas-François Poirier (Perry) became the first Acadian Member of Parliament, twenty years after becoming the first Acadian elected to the House of Assembly of Prince Edward Island.
Death of Edward Barron Chandler
Edward Barron Chandler, a Father of Confederation, died in Fredericton, NB. Born to a prominent family, Chandler was deeply involved in the region’s politics. He was interested in constructing a Maritime rail line to Québec City and developing ties with the United States. Chandler also fought for Acadian language and cultural rights.
First National Acadian Convention
The first National Acadian Convention was held in Memramcook, New Brunswick. Chaired by MP Pierre-Amand Landry, the convention drew over 5,000 people and saw the establishment of National Acadian Day on 15 August, Assumption Day.
Flag of Acadia adopted
In 1884, Miscouche hosted the historic second Convention nationale acadienne (National Acadian Convention), during the course of which delegates adopted all the national symbols Acadians use today: the flag (the French tricolour with a yellow star in the blue stripe), the national anthem (Ave Maris Stella), the motto (“L’Union fait la force” or “Unity makes strength”) and the crest.
Pascal Poirier appointed to the Senate
A leading figure of the Acadian Renaissance, Pascal Poirier, of Shediac, NB, became the first Acadian appointed to the Senate.
Launch of the L’Évangéline
Established by Valentin Landry in Digby, Nova Scotia, this Acadian newspaper was moved to Moncton, New Brunswick in 1905 and published until 1982.
College Sainte-Anne, NS is founded
College Sainte Anne (today Université Sainte-Anne) was founded at Church Point, Nova Scotia by the Eudist Fathers and offered instruction in French.
Édouard-A. LeBlanc becomes the first Acadian Bishop
After decades of petitions from Acadians, the Vatican appointed the first bishop of Acadian origin to the Episcopal seat of Saint John, New Brunswick.
Birth of Gilbert Finn
Born in Inkerman Ferry, NB, Gilbert Finn is an Acadian businessman. After working 37 years at the Assumption Mutual Life Assurance Co, he served on the Atlantic Provinces Economic Council and the Economic Council of Canada, was president of the Université de Moncton and was active in Acadian and New Brunswick community groups. His service to his people and province was rewarded with membership in the Order of Canada. Upon his retirement in 1987 he was appointed lieutenant-governor of New Brunswick, the second person of Acadian descent to be so honoured. He served in this capacity until 1994.
Peter John Veniot becomes NB premier
Born in Richibucto, NB, Peter John Veniot, "Pierre," was the first Acadian NB premier and served from 1923 to 1925. He succeeded W.E. Foster as premier in 1923 and supported public ownership of the provincial hydro system and the Maritime Rights Movement. He was recognized as the leader of Acadian Liberalism. Following the defeat of his party in 1925, he ran successfully as MP for Gloucester and was appointed postmaster general by Prime Minister W.L. Mackenzie King. He sat as an MP until his death in 1936.
Birth of Antonine Maillet
Celebrated Acadian novelist Antonine Maillet was born at Bouctouche, NB.
Arts, Culture and Identity Historical Figures and Acadians
Birth of Angèle Arsenault
Angèle Arsenault was a pioneering Acadian singer-songwriter. She was renowned for her catchy, upbeat melodies, playful social commentary and distinctive humour. She was perhaps best known for the songs “Évangéline, Acadian Queen,” “Je veux toute la vivre ma vie,” and the Acadian anthem “Grand-Pré.” An Officer of the Order of Canada and a Member of the Order of Prince Edward Island, she received the Ordre de la Pléiade from the Association of French-Speaking Parliamentarians for her role in promoting French language and culture.
Birth of Jacques Savoie
Jacques Savoie, Acadian musician, author, screenwriter (born 3 February 1951 in Edmundston, NB). Savoie has left his mark on French-Canadian literature, television and film. A founding member of the Acadian musical group Beausoleil Broussard, he is also the author of close to 20 novels, including Raconte-moi Massabielle and Les Portes tournantes, both of which have garnered many international awards and been made into films.
Birth of Raymonde April
Photographer Raymonde April, whose practice has influenced the development of photography in Québec and Canada, was born at Moncton, NB.
Louis J. Robichaud becomes premier of NB
Elected leader of the NB Liberal Party in 1958, Louis Joseph Robichaud led it to victory over Hugh J. Flemming in 1960, served as attorney general between 1960 and 1965, and as minister of youth in 1968. The first Acadian elected premier of NB, he introduced far-reaching social reforms through the centralizing Programme of Equal Opportunity. His government passed an Official Languages Act, established Université de Moncton, increased Acadian administrative influence, and encouraged the mining and forestry industries.
Birth of Roch Voisine
Roch Voisine, popular award winning Quebec singer, was born at St Basile, NB.
Université de Moncton is founded
Université de Moncton was founded by the New Brunswick legislature in accordance with the recommendations of a royal commission. Université de Moncton began with the amalgamation of three institutions which agreed to suspend their charters in order to become affiliated colleges: Saint-Joseph (founded 1864), Sacré-Coeur (1899) and Saint-Louis (1946). As amended in 1977, the university's charter authorized campuses in each of New Brunswick's three francophone regions: Moncton, Edmundston and Shippagan.
Kouchibouguac National Park Established
Kouchibouguac National Park was established. Situated on the eastern New Brunswick shore of Northumberland Strait, the park is a delicate blend of beaches, sand dunes and salt marshes. A 25 km long barrier-island system shelters lagoons from the often violent sea. Several rivers flowing across the park inspired its Mi'kmaq name "river of the long tides."
New Brunswick's Bilingual Acts
New Brunswick became the first province to draft statutes in both official languages.
Acadian Historical Village Opens
The Acadian Historical Village (Village historique acadien) is an ambitious living history site located on the Rivière-du-Nord near Caraquet, NB, in the heart of the Acadian Peninsula. It presents the rich tangible and intangible cultural heritage of the large Acadian population who settled in this province.
Opening of the first Jeux de l’Acadie
The first Acadian Games (Jeux de l’Acadie) were held in Moncton from 29 August to 1 September 1979.
Antonine Maillet wins Prix Goncourt
For her novel Pélagie-la-Charrette, Acadian writer Antonine Maillet became the first non-French citizen to win France's most prestigious literary prize, the Prix Goncourt.
First Congrès mondial acadien
The first Congrès mondial acadien (World Acadian Congress) was held in Moncton and various communities of southeastern New Brunswick from 12 August to 22 August 1994.
Rose-Marie Losier-Cool appointed to the Senate
Born in Tracadie-Sheila, NB, Rose-Marie Losier-Cool became the first Acadian woman appointed to the Senate.
Bastarache Named New Supreme Court Justice
PM Jean Chrétien named Justice Michel Bastarache to fill the vacancy left on the Supreme Court by Gerard LaForest. He became the first Acadian appointed to the Supreme Court of Canada.
Thériault Becomes Premier
Camille Henri Thériault was sworn in as premier of New Brunswick.
Conservatives Win in NB
The New Brunswick Progressive Conservative Party won a surprising landslide victory in the provincial election. Thirty-three-year-old Bernard Lord became premier.
Moncton becomes a bilingual city
Moncton, NB, became the first officially bilingual Canadian city.
Herménégilde Chiasson is installed as New Brunswick's lieutenant-governor
Herménégilde Chiasson was born 7 April 1946 in Saint-Simon, NB. He is an artist, poet, playwright, film director and lieutenant-governor of New Brunswick. An Officer of the Order of Canada, winner of the Governor General’s Literary Award, and New Brunswick's 29th lieutenant-governor, Chiasson is considered the father of Acadian modernism and is one of Canada's foremost advocates of Acadian culture and the arts. He is also notable for his insistence upon Acadian culture being a living culture rather than a persecuted and exiled one.
Crown acknowledges deportation of the Acadian people
In a royal proclamation, Governor General Adrienne Clarkson recognized the responsibility of the British Crown in the decision to deport the Acadian people in 1755 and its tragic consequences. Since 2005, 28 July has been designated Day of Commemoration of the Great Upheaval.
Day of Commemoration of the Great Upheaval
To mark the 250th anniversary of the deportation of the Acadian people in 1755, 28 July officially became Canada's Day of Commemoration of the Great Upheaval, as set by the Royal Proclamation of 6 December 2003.
Edith Butler receives the Governor General’s Performing Arts Award for Lifetime Achievement
Born in 1942 in Paquetville, NB, Édith Butler has popularized a number of traditional Acadian songs.
Death of Roméo A. LeBlanc
A fluently bilingual Acadian, LeBlanc was selected by PM Jean Chrétien in 1994 to succeed Ray Hnatyshyn as Governor General of Canada. Roméo LeBlanc was the first Maritimer and first Canadian of Acadian descent to hold the vice-regal office.
France Daigle wins the Governor General’s Literary Award
France Daigle, an Acadian author born 18 November 1953 in Dieppe, a suburb of Moncton, New Brunswick, is the leading representative of postmodern Acadian literature. Her work has sparked a great deal of interest in Québec, English Canada, and other parts of the Francophonie. She won the Governor General’s Literary Award for her masterpiece entitled Pour sûr (2011).
Death of Angèle Arsenault
Brian Gallant elected premier of New Brunswick
Brian Alexander Gallant was born 27 April 1982 in the Acadian community of Shediac Bridge, New Brunswick. He was a lawyer and leader of the New Brunswick Liberal Party. At 32 years of age, he became the country’s youngest premier. Gallant is the son of Pierre Gallant, who is of Acadian heritage, and Marilyn Scholten, the daughter of Dutch immigrants.
Death of Gilbert Finn
Born 3 September 1920 in Inkerman Ferry, NB, Gilbert Finn is an Acadian businessman. After working 37 years at the Assumption Mutual Life Assurance Co, he served on the Atlantic Provinces Economic Council and the Economic Council of Canada, was president of the Université de Moncton and was active in Acadian and New Brunswick community groups. His service to his people and province was rewarded with membership in the Order of Canada. Upon his retirement in 1987 he was appointed lieutenant-governor of New Brunswick, the second person of Acadian descent to be so honoured. He served in this capacity until 1994.
Related Timelines All Timelines


FATAH: India takes giant leap for mankind by decriminalizing homosexuality
Tarek Fatah
Gay rights activists hold a flag as they celebrate amid heavy downpour after the country's top court struck down a colonial-era law that made homosexual acts punishable by up to 10 years in prison, in New Delhi, India, Thursday, Sept. 6, 2018. (AP Photo/Altaf Qadri)
When the German thinker Goethe said, “I am what I am, so take me as I am,” little could he have imagined that his profound quote would centuries later be invoked to decriminalize homosexuality and end centuries of stigma faced by the LGBTQ community in the ancient civilization that has given so much to the world — India.
On September 6, the Supreme Court of India delivered a decision that will be forever remembered as one giant step forward for humanity. It decriminalized homosexuality in a 495-page decision that included references to Shakespeare, John Stuart Mill and on precedent set in other societies, including our very own Canada.
The supreme court scrapped section 377 of the Indian constitution that had banned gay sex, ending the pariah status of the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community in the world’s largest democracy.
The five judges issued four separate but concurrent judgments to seal the matter, ending a decades-long battle in which India’s religious right demonized the LGBTQ community in the most vicious and derogatory manner, but failed to pass the test of their much-touted moral and sanctimonious lecturing that brought Christian priests hugging Islamic clerics while a segment of the Hindus sulked, failing to recognize that Hinduism had never treated gay sex as a ‘sin’ or an immoral act.
Chief Justice Dipak Misra quoted Shakespeare as he read out the unanimous ruling of five judges to legalize gay sex.
“What’s in a name? That which we call a rose by any other name would smell as sweet,” Misra said, borrowing a phrase from “Romeo and Juliet,” as he overturned the homophobic Section 377 of the Indian constitution.
As I watched the LGBTQ community, their families and countless supporters dance in joy in Delhi, the reaction of the Christian churches and the Islamic institutions was one of dismay and anger.
The self-appointed All India Muslim Personal Law Board (AIMPLB) denounced the Supreme Court judgement, tweeting: “Legalizing homosexuality is against Indian values and culture. No religion allows immorality. The government must pass a bill to protect the rights of women as they are the major victims of legalised homosexuality.”
The Mullahs who run the AIPLMB were roundly denounced by even the Muslim community.
Young Muslim writer and activist from Kashmir, Irfa Jan tweeted back: “Who gave you guys [AIPLMB] the legitimacy to talk on behalf of All India Muslims? Were you elected by them as your name suggests? An oddly chosen body cannot represent 100 million diverse, multilingual, multicultural people. YOU DO NOT REPRESENT ME.”
As if the homophobic reaction by the Muslim Board was not enough, another group of India’s Islamic clerics, the Jamiat Ulema-e-Hind joined forces. The orthodox right-wing group’s General Secretary Maulana Mahmood Madani said, “Homosexuality is against nature, religion and cultural values of India. It should not have been allowed.”
At the last sitting of the court while the Muslim groups refrained from pushing forward their objections, three Christian groups continued to argue against decriminalizing gay sex, but could not sway any of the five justices.
The following words of the Indian Supreme Court can serve all of humanity as far as human rights are concerned. The justices said:
“One defines oneself. That is the glorious form of individuality. … Sans identity, the name only remains a denotative term. Therefore, the identity is pivotal to one‘s being. Life bestows honour on it and freedom of living, as a facet of life, expresses genuine desire to have it. … And the sustenance of identity is the filament of life. It is equivalent to authoring one‘s own life script where freedom broadens every day.”
“Identity is equivalent to divinity,” they declared.


Tag: pco
I Love Taxi Drivers
Ok I don’t really, the majority of my worst incidences have been with taxi drivers and they seem to be invincible! From my experience the police pass any reports to the PCO and the PCO hold their hands up and say it’s up to the police to sort it out.
The public carriage office in its current state is a bit of a shambles, I have been provided a small amount of inside knowledge from someone who was involved with the PCO from a day-to-day basis on a professional level. I won’t go into detail at present, it would be a very long post but the end result is taxi drivers in London are basically untouchable and a few of them act as if they know that.
I’ve reported various incidences of varying degrees to the PCO, in every case I’ve not had a positive response, most of them result in a ‘It’s not our job to the police the roads’ and a few result in ‘we can’t view youtube videos so it’s your word against theirs’. It normally ends there, they are very understaffed and just don’t have time to look into these cases in enough detail.
I’ve tried reporting it to the Police but the MET handed over regulation and licensing of hackney carriages to TFL in 2000 and they seem to try to push the reports on TFL/PCO.
So far I’ve gotten not a single result from anything that has happened with a black cab. If you follow what I’ve published on youtube then you will know there are some real shockers.
I have had a few incidences which I’ve been told will be put on the driver’s record, but note these where not confirmed and the information did not come from someone who worked at the PCO. So I have no way to be certain.
Transport for London have provided a handy document that outlines the laws which govern hackney carriages and it states
In this Abstract, ‘The Licensing Authority’ means Transport for London (TfL) which will exercise the duties imposed by the London Cab Order 1934 as amended by the Greater London Authority Act 1999.
So it is up to TFL/PCO to apply the laws in that document. In the document is the Standard Scale, which is the different fines that TFL/PCO are to apply to drivers when the break various laws, unfortunately the fines are maximum and do not have to be that exact amount.
Level 1 = £200
Level 3 = £1,000
Lets highlight a few of the laws and what fines should be applied to the drivers that break them.
39. Various acts of misbehaviour by taxi driver (Act of 1843 s28; Act of 1831 s 56)
(1) The following offences are punishable by penalty (Level 1) or two months imprisonment:
(a) Wanton or furious driving.
(b) Causing hurt or damage to any person by carelessness or wilful misbehaviour.
(c) Drunkenness during employment.
(d) Use of insulting or abusive language during employment.
(e) Use of insulting gestures during employment.
(f) Any misbehaviour during employment.
(2) The following offences are punishable by penalty (Level 1 )
(a) Injuring or endangering the life, limbs or property of any persons by intoxication, wanton or furious driving or any other wilful misconduct.
(b) Using abusive or insulting language or rude behaviour towards any person.
(c) Assaulting or obstructing any police officer in the execution of his duty.
(3) This type of behaviour is also contrary to laws of general application, for example the Public Order Act 1986, carrying where appropriate heavy fines and/or imprisonment.
So it is up to TFL/PCO to deal with drivers who; drive dangerously, injury someone, damage someones property, swear at someone, use insulting gestures.
In several case I have been sworn at, threatened and had people driving dangerously around me. So that would mean that several drivers should have gotten fines but instead they may have a mark on their record or they got away with it.
I guess I will have to push the PCO next time I have an incident with a taxi and get them to properly deal with the driver. At present it’s a joke and I get the feeling that taxi drivers are currently untouchable which is a problem when some of them think you shouldn’t be on the road and they are king.


Former Armenian Leader Freed From Pretrial Detention
FILE - Armenia's President Robert Kocharyan speaks to the media after casting his ballot during a parliamentary election in Yerevan, May 12, 2007.
TBILISI, GEORGIA - An Armenian court on Saturday ordered former President Robert Kocharyan freed on bail from pretrial detention, local news agencies reported.
Kocharyan, 64, was arrested last July after peaceful protests drove his former ally and successor, Serzh Sarksyan, from power and propelled opposition leader Nikol Pashinyan into the prime minister's job.
Kocharyan, who was president from 1998 to 2008, has been charged with acting unlawfully by introducing a state of emergency in March 2008, following a disputed election. At least 10 people were killed in clashes between police and protesters.
He was freed on bail of 1 million drams ($2,000). He faces up to 15 years in prison if found guilty.
Kocharyan told Reuters earlier this month that powerful opposition forces were coming together to challenge the country's new leadership soon, and that he hoped to be among them.
Experts See Russia Fingerprints on North Korea's New Missile
The three new missiles North Korean leader Kim Jong Un has tested over the past week are eerily familiar to military experts: They look just like a controversial and widely copied missile the Russian military has deployed to Syria and has been actively trying to sell abroad for years. Ending a pause in ballistic missile launches that began in late 2017, and alarming North Korea's neighbors, Kim personally supervised the launch of the first missile from the country&#39…
US-Backed Syrian Forces Form Armenian Unit
U.S.-backed Syrian Democratic Forces (SDF) this week announced the establishment of a new force made up of ethnic Armenians. The SDF is a Kurdish-led multiethnic military alliance that played a key role in the fight against the Islamic State (IS) terror group in Syria. The SDF liberated the last IS stronghold of Baghuz in eastern Syria last month and now controls more than one third of Syria's territory. "We will follow the path of our martyrs…
By Sirwan Kajjo
France Holds First 'Armenia Genocide' Remembrance Day
France held its first "national day of commemoration of the Armenian genocide" on Wednesday, provoking an angry reaction from Turkish leader Recep Tayyip Erdogan. Troops from the Ottoman Empire — which preceded modern-day Turkey — were responsible for massacres and forced deportations of Armenians from 1915, but Turkey has always denied that the killings amounted to genocide. France was the first major European country to…
Ukrainian Diaspora Voters Show Starkly Different Political Preferences for Kyiv
This story originated in VOA's Ukrainian Service. Pete Cobus contributed to this report. LONDON - Ukrainians who live abroad strongly prefer sitting President Petro Poroshenko to other candidates in last weekend’s first-round presidential election, contradicting the choice of voters who reside within the eastern European nation.According to official tallies of votes cast in Ukraine,…
By Bogdan Tsioupine


In Keynote Speech, Bennet Says New Approach Needed to Support, Reward and Retain Talented Teachers in America's Public Schools
In a Speech at Center for American Progress, Bennet Emphasizes Central Role Teachers Play in Improving Student Outcomes
Washington, DC - In a keynote speech before the Center for American Progress, Michael Bennet, U.S. Senator for Colorado and former Superintendent of the Denver Public Schools, highlighted the need for a new approach to support, reward and retain talented teachers in America's public schools and stressed the important role they will play in improving student outcomes and preparing our kids for the new economy.
"We have got to come together and design the system that's a 21st Century approach to attracting and retaining teachers to our schools," said Bennet. "It is a national conversation that we should be having because this is a national issue that we have. I think that we should be doing everything that we can to encourage the kind of innovation that we see in Denver and see in other places."
In his remarks, Bennet highlighted the need to fundamentally transform our approach to recruiting and retaining talented teachers in America's public schools, and cited steps taken by the Denver Public Schools drive student achievement and improve student outcomes.
Bennet also stated that school districts across the country have proven that improvement is possible, and that the country must continue to identify and bring to scale successful models that drive student achievement and prepare our kids for the new economy.
Click here to access the event footage. Scroll to minute 5 to watch Bennet's presentation and his answers to audience questions.
A full transcript of Bennet's remarks is included below:
Thank you all, it's great to see you this morning. I really appreciate your letting me have the chance to come. I'm going to try to be as brief as possible. Having said that, I'll break that promise. And we'll have some Q&A afterwards. I want to recognize CAP's great work here and acknowledge two people from Denver with whom I have had a very cherished relationship. My union President Kim Ursetta, who's here, who ran the Denver Classroom Teachers Association, with whom I battled, with whom we struggled, and with whom we made a huge difference together. And with Brad Jupp, who worked with me side by side from the day I became Superintendent, Brad was a union leader in the Denver Public Schools for many years. He came over to work with me and to help refine and develop Procomp, and he is one of the true educational reformers in this country now working for Arne Duncan. And it is a great pleasure to see you. Even though we work in the same town, we never ever see each other anymore.
And to CAP, I want to thank you, John, for focusing on what really matters, rather than the reform of the day, the flavor of the day. But to understand that fundamentally and at its core, education, just like almost everything else, comes down to the human beings that are actually in the class. And I'm very grateful for your focus on that and for the focus on the panels on that and the papers you are going to hear. I looked at them last night, and there's a lot of good stuff in there, so you are going to have a good conversation today.
I always start by reminding people what we are really dealing with here because not enough people in the country understand what the outcomes are for kids in our country. I'm going to give you a couple statistics, I'm not going to bore you with a bunch, but I'll give you a couple. One, when I took the job as Superintendent of the schools, one of the most alarming statistics that I read was that on the 10th grade math test administered by the state, in a school district of 75,000 children and a city of 550,000 people, 33 African-American students were proficient on our 10th grade math test, and 61 Latino students were proficient on our 10th grade math test. Fewer than four classrooms-worth of kids in that 75,000-child school district proficient on a test that measures a junior high school standard of mathematical proficiency in Europe.
We know that children in poverty by the time they get to the 4th grade are already two to three grade levels behind their middle-class peers. And we know that today's 4th graders that are living in poverty, stand a one in two chance of graduating from high school and a one in 10 chance of graduating from college. Those are the same odds by the way, their older brothers and older sisters had and the same odds their parents had - a 1 in 10 chance of graduating.
Our economy has already transformed itself. If you look at the last job creation we had in the United States of America, we created about 5 million jobs that required a four-year degree. We created somewhere in the neighborhood of 2 or 3 million jobs that required something less than that in terms of post-high school education. We lost jobs for people without high school diplomas. We lost jobs for people with a high school diploma, but not any work in college. That trend is not going to reverse itself. So these gaps that we have, that we confront today, if we do nothing different, are only going to grow. And they are going to grow exponentially.
We're not going to have time today to talk about all of the things that we need to change in our delivery of public education, which by in large owes its design to Colonial America and to the period right around World War II. We could take up the whole week talking about what we could do, but this is what I want to talk about today. In my view, there's nothing more important for us to recognize, than that we no longer live in labor market that discriminates against women and says you have two professional choices - one is being a teacher and one is being a nurse. Our entire system of training, of compensation, the way we think about retaining teachers, evaluating teachers, the way we think about inspiring teachers, maybe that's the most important thing, belongs to an era that no longer exists. And we got away with the system that used that discrimination to subsidize our public education system and to say, you know what, we are going to have the very best people in our classrooms, willing to teach Julius Caesar every year for 30 years, because nobody is going to ask them to do anything else.
This is not a political trope for me. This is the hardest job anybody can do, is teaching in one of these urban school districts. It's harder than whatever anybody else here does besides the teachers that are here. And we have got to come together and design the system that's a 21st Century approach to attracting and retaining teachers to our schools. And what I would just submit at the end of that, I'm going to say one more thing, is that the policy conversation we're having right now, is not at risk of actually dealing with the issue that we're confronting. It is too narrow, it is too small, it is a national conversation that we should be having, because this is a national issue that we have. And I think that we should be doing everything that we can to encourage the kind of innovation that we see in Denver and see in other places, encourage the kind of discussions that Kim and I had. They were tough, but they were worth it. And it shows it can be done.
The last thing I want to say is this, and this is something I really thought hard about last night before I came. One of the acquired learnings that I had, based on my time in Denver, is that there is enormous reform fatigue in this country. There's huge reform fatigue among our teachers. There's huge reform fatigue among our principals. And that's a particular problematic when you're dealing with a culture, that is defined, as much as this culture is, by mistrust and by worry. And so, while I used to say that our reform, our instructional reform, was absolutely breathtaking in its lack of originality, and I continue to believe that, our approach was different. And for reasons that I don't understand, no one else seems to be doing it.
So, let me give this to you as an idea for the people that are actually thinking about the policies and asking the question of yourself: how do we actually get this done? How do we move from a good idea, to getting it done? How do we deal with the conflict that inevitably arises in schooling? And, I think that the first piece of that is recognizing how tough the culture is and reasons why. It's hard when you've dedicated your life to teaching and your kids don't seem to make any progress and you lose all sense of your efficacy or collective efficacy, and that's tough. That's a tough starting point.
So, here were my two ideas on this and I thought they worked out well. One was, before I became Superintendent I asked Brad about this, I said that I would meet every morning, virtually every morning, with a group of 15 of our principals for two hours in their schools. Every three weeks I saw every principal in the school district for two hours, for the nearly four years that I was Superintendent of schools. And the conversations were not about who got left on the bus, or was the boiler broken, the conversations were all about teaching and learning.
I'll give you an example, it was this narrow. For three weeks, we took around the same one and half page piece of student work. It's important for people to look at student work. Here's how professional development goes in America on student work. It's important that you look at student work. Go back to your building and tell your teachers they need to look at student work. We took the same one and half page piece around with us and we would pass it out to the principals. It was a 4th grader's writing, but we did it the same writing at every level. And the same thing would happen every single time. Which is, people would look at this, and they would say I can't read this, this doesn't make any sense to me, this looks like a foreign language. And just when they would crescendo, my chief academic officer would say, based on what you've read what are Nancy's strengths as a writer. So everybody would have to dive back into the piece of paper and for an hour we would have a discussion where people would say Nancy writes from left to right, she has some sense of story structure, she spells high frequency words correctly. We'd say, why is that, and they would say, well maybe she had a vocabulary test and we'd say maybe. Or maybe her teacher has a word wall in her classroom that she's using to scaffold her instruction. The point is we don't know, but let's not make an assumption about that. And then, they would say she has stamina as a writer. Which would turn out, for reasons that I am not going to bore you today, not to be true.
Then the last part of our conversation was how do you take what you just went through and what you just learned back to your building and engage your teachers in this conversation, so that the instruction changes, not next year, not after professional development next summer, but in the next period, for Nancy and for all the Nancy's that are in every school district in our country who are writing something that our own folks are saying they can't read. That had an enormous impact on the culture because we built a principal core that understood that their job was not to keep the system the same; it was to change the system. And by in large they understood that their job was not to grind down the people that were working with our kids but to try to support them. And, I don't remember the numbers exactly but, the DCTA did a survey of its members every year and there was a question on that survey that said from the teachers. The question was, my principal supports me as a professional in the building and respects me. That went in a year from something like 35 percent yes, to something like 71 percent yes. Can you imagine how much easier it is to do the kinds of reforms you all care about and I'm thinking about when people feel like they're being respected by their principals.
The second thing I did was that I said I would meet with every faculty in the school district every single year. We had 150 schools, give or take, and we spent an hour. Five minutes at the beginning is all I took and the rest of it was completely open and completely free form. And the point of it was, the first year to be a piñata. To have people say, which they said, the first year, Kim will remember this, we were here before you got here, and we are going to be here after you leave. And you know nothing about what it is we do every day. To which I could say you're correct about that, that's why I'm here. But the next year what it allowed us to do is we were implementing the reforms, was to get feedback directly from the teachers, unmediated by the bureaucracy. And they would say things, like you must not have intended this, or you guys are completely out of your minds for doing this.
The one I remember that comes to mind today is a very simple one, we had gone to standard-based report card, no more ABC and D and F, but 1,2,3, and 4. The standard-based report card. Because of the reform that we did, because of what I did as Superintendent, teachers were no longer able to print their report cards at their desk when they needed them for their kids. The IT department was printing these things in the building downtown and then trucking them to our teachers when it was convenient. Because of their feedback, we changed that, we took that pain point away from people and we didn't, eh, other things. Except for Kim Ursetta's. But no, but there things like that, that we changed.
And in January of the second year, we cut a video that said based on the feedback you guys have given us, here are all the changes that we're making to the reform that we're engaged in. Something that had never happened in the history of the Denver Public Schools, which was people actually listening. So my final observation is this, we need to radically change the delivery of public education in this country. But we're not going to do it if we don't intend to, the cultural work that has to be done to make sure we go faster on this, rather than slower on this. Thank you.
Permalink: https://www.bennet.senate.gov/public/index.cfm/2010/3/in-keynote-speech-bennet-says-new-approach-needed-to-support-reward-and-retain-talented-teachers-in-america-039-s-public-schools