Skip to content Skip to sidebar Skip to footer
Accueil / what does botulinum toxin do to the body

what does botulinum toxin do to the body

Enregistrer un commentaire

Neurotoxic protein produced by Clostridium botulinum

Botulinum toxin A
Botulinum toxin 3BTA.png

Ribbon diagram of third structure of Flacon (P0DPI1). PDB entry 3BTA.
Clinical data
Trade names Botox, Myobloc, Jeuveau, others
AHFS/Drugs.com Monograph
MedlinePlus a619021
License data
  • US  DailyMed:Jeuveau
Pregnancy
category
  • AU: B3
Routes of
administration		 IM (approved), SC, intradermal, into glands
ATC code
  • M03AX01 (WHO)
Legal condition
Legal status
  • AU: S4 (Prescription only)
  • Usa: ℞-merely
  • EU: Rx-simply
Identifiers
CAS Number
  • 93384-43-1 ☒ N
DrugBank
  • DB00083 ☒ N
ChemSpider
  • none
UNII
  • E211KPY694
KEGG
  • D00783
  • D08957
ECHA InfoCard 100.088.372 Edit this at Wikidata
Chemical and physical data
Formula C 6760 H 10447 North 1743 O 2010 Due south 32
Molar mass 149323.05 g·mol−i
☒ N check Y  (what is this?) (verify)
Bontoxilysin
Identifiers
EC no. 3.iv.24.69
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM contour
PDB structures RCSB PDB PDBe PDBsum
Factor Ontology AmiGO / QuickGO

Botulinum toxin (BoNT), often shortened to Botox, is a neurotoxic poly peptide 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, thus causing flaccid paralysis.[2] The toxin causes the illness botulism. The toxin is besides used commercially for medical and corrective purposes.

The seven master types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and Chiliad).[3] [four] New types are occasionally plant.[five] [six] Types A and B are capable of causing disease in humans, and are also used commercially and medically.[7] [8] [9] Types C–Yard are less common; types Due east and F tin cause disease in humans, while the other types cause disease in other animals.[10] Botulinum toxin types A and B are used in medicine to treat various musculus spasms.

Botulinum toxins are the nearly potent toxins known.[xi] Intoxication tin can occur naturally as a effect of either wound or intestinal infection or past ingesting formed toxin in nutrient. The estimated human lethal dose of type A toxin is 1.iii–2.1 ng/kg intravenously or intramuscularly, x–13 ng/kg when inhaled, or 1000 ng/kg when taken by rima oris.[12] Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA), Dysport/Azzalure (abobotulinumtoxinA),[xiii] Xeomin/Bocouture (incobotulinumtoxinA),[14] and Jeuveau (prabotulinumtoxinA).[15] [16]

Medical uses [edit]

Botulinum toxin is used to care for a number of therapeutic indications, many of which are not part of the approved drug label.[ medical commendation needed ]

Muscle spasticity [edit]

Botulinum toxin is used to care for a number of disorders characterized by overactive musculus movement, including cerebral palsy,[7] [viii] post-stroke spasticity,[17] post-spinal cord injury spasticity,[xviii] spasms of the caput and neck,[19] eyelid,[twenty] vagina,[21] limbs, jaw, and song cords.[22] Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the esophagus,[23] jaw,[24] lower urinary tract and float,[25] or clenching of the anus which can exacerbate anal fissure.[26] Botulinum toxin appears to be effective for refractory overactive bladder.[27]

Other muscle disorders [edit]

Strabismus, otherwise known as improper middle alignment, is caused by imbalances in the deportment of muscles that rotate the eyes. This status tin sometimes be relieved by weakening a musculus that pulls as well strongly, or pulls against one that has been weakened by illness or trauma. Muscles weakened by toxin injection recover from paralysis afterwards several months, then injection might seem to need to be repeated, but muscles accommodate to the lengths at which they are chronically held,[28] so that if a paralyzed musculus is stretched by its adversary, it grows longer, while the antagonist shortens, yielding a permanent effect.[29] If binocular vision is good, the brain machinery of motor fusion, which aligns the eyes on a target visible to both, tin can stabilize the corrected alignment.[30]

In January 2014, botulinum toxin was canonical by United kingdom of great britain and northern ireland'southward Medicines and Healthcare products Regulatory Bureau for handling of restricted ankle movement due to lower-limb spasticity associated with stroke in adults.[31] [32]

On 29 July 2016, the U.S. Food and Drug Administration (FDA) approved abobotulinumtoxinA for injection for the treatment of lower-limb spasticity in pediatric patients two years of age and older.[33] [34] AbobotulinumtoxinA is the commencement and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity.[35] In the U.S., the FDA approves the text of the labels of prescription medicines and for which medical atmospheric condition the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known every bit off-characterization use.[36] Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.[37]

Excessive sweating [edit]

AbobotulinumtoxinA (BTX-A) has been approved for the treatment of excessive underarm sweating of unknown cause, which cannot be managed past topical agents.[22] [38]

Migraine [edit]

In 2010, the FDA canonical intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache.[39]

Cosmetic dermatology [edit]

Botulinum toxin being injected in the human face up

In cosmetic applications, botulinum toxin is considered relatively safe and effective[40] for reduction of facial wrinkles, especially in the uppermost third of the face.[41] Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, and in the U.South. only, Jeuveau from Evolus, manufactured past Daewoong.[xvi] The effects of current botulinum toxin injections for glabellar lines ('xi'south lines' betwixt the eyes) typically terminal two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect.[41] Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin.[41] Smoothing of wrinkles is usually visible three to five days later on injection, with maximum issue typically a calendar week following injection.[41] Muscles tin can be treated repeatedly to maintain the smoothed appearance.[41]

Other [edit]

Botulinum toxin is also used to treat disorders of hyperactive fretfulness including excessive sweating,[38] neuropathic pain,[42] and some allergy symptoms.[22] In addition to these uses, botulinum toxin is beingness evaluated for utilise in treating chronic pain.[43] Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion.[44] The utilise of botulinum toxin A in children with cerebral palsy is safe in the upper and lower limb muscles.[7] [8]

Side effects [edit]

While botulinum toxin is generally considered safe in a clinical setting, serious side effects from its employ can occur. About unremarkably, botulinum toxin can be injected into the wrong muscle grouping or with time spread from the injection site, causing temporary paralysis of unintended muscles.[45]

Side furnishings from cosmetic use more often than not result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and problem swallowing. Side effects are not limited to direct paralysis, however, and can likewise include headaches, flu-like symptoms, and allergic reactions.[46] Just as cosmetic treatments only final a number of months, paralysis side effects tin have the same durations.[ citation needed ] At least in some cases, these furnishings are reported to dissipate in the weeks after handling.[ citation needed ] Bruising at the site of injection is not a side event of the toxin, merely rather of the fashion of assistants, and is reported as preventable if the clinician applies force per unit area to the injection site; when information technology occurs, it is reported in specific cases to last 7–11 days.[ commendation needed ] When injecting the masseter muscle of the jaw, loss of muscle function can outcome in a loss or reduction of ability to chew solid foods.[46] With continued high doses, the muscles can cloudburst or lose force; enquiry has shown that those muscles rebuild afterward a suspension from Botox.[47]

Side furnishings from therapeutic use can exist much more than 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 utilize. These can arise from paralysis of critical muscle groups and can include arrhythmia, middle assail, and in some cases, seizures, respiratory abort, and death.[46] Additionally, side furnishings common in cosmetic use are also common in therapeutic utilize, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes.[46]

In response to the occurrence of these side effects, in 2008, the FDA notified the public of the potential dangers of the botulinum toxin every bit a therapeutic. Namely, the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating musculus spasticity in children treated for cerebral palsy.[48] In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their power to spread from the injection site.[49] Still, the clinical employ of botulinum toxin A in cerebral palsy children has been proven to be condom with minimal side effects.[7] [8] Additionally, the FDA appear name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper utilize. Botox and Botox Cosmetic were given the INN of onabotulinumtoxinA, Myobloc as rimabotulinumtoxinB, and Dysport retained its INN of abobotulinumtoxinA.[49] In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each.[fifty] A like alarm was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.[51]

Role in illness [edit]

Botulinum toxin produced past Clostridium botulinum is the crusade of botulism.[xx] Humans most ordinarily ingest the toxin from eating improperly canned foods in which C. botulinum has grown. However, the toxin can too be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin inside the intestine and can crusade a condition known as floppy babe syndrome.[52] In all cases, the toxin tin can then spread, blocking nerves and musculus function. In severe cases, the toxin tin can cake fretfulness controlling the respiratory system or center, resulting in death.[i] Botulism can be difficult to diagnose, as it may announced like to diseases such as Guillain–Barré syndrome, myasthenia gravis, and stroke. Other tests, such as encephalon scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can exist administered. In an effort to remove contaminated food that remains in the gut, enemas or induced airsickness may exist used.[53] For wound infections, infected fabric may be removed surgically.[53] Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not opposite existing nerve damage. In astringent cases, mechanical respiration may be used to support patients suffering from respiratory failure.[53] The nerve impairment heals over time, by and large over weeks to months.[10] With proper handling, the case fatality rate for botulinum poisoning can be greatly reduced.[53]

Ii preparations of botulinum antitoxins are available for handling of botulism. Trivalent (serotypes A, B, E) botulinum antidote is derived from equine sources using whole antibodies. The 2d antitoxin is heptavalent botulinum antitoxin (serotypes A, B, C, D, Due east, F, G), which is derived from equine antibodies that have been contradistinct to make them less immunogenic. This antitoxin is effective against all main strains of botulism.[54] [6]

Mechanism of activity [edit]

Target molecules of botulinum neurotoxin (abbreviated BoNT) and tetanus neurotoxin (TeNT), toxins interim inside the axon last.[55]

Botulinum toxin exerts its event past cleaving central proteins required for nerve activation. First, the toxin binds specifically to fretfulness that use the neurotransmitter acetylcholine. Once bound to the nerve last, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis.[56] As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin that triggers it to button beyond the vesicle membrane and into the cell cytoplasm.[1] BoNTs recognize distinct classes of receptors simultaneously (gangliosides, synaptotagmin and SV2).[57] One time inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular prison cell membrane,[56] 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, and so becomes activated when cleaved by its own proteases.[22] The active form consists of a ii-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bail to a 50-kDa light chain polypeptide.[58] The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, besides as the domain responsible for mediating translocation of the low-cal chain into the cell cytoplasm as the vacuole acidifies.[1] [58] The lite chain is a M27-family unit zinc metalloprotease and is the active office of the toxin. It is translocated into the host jail 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 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings.[ane] This blockage is slowly reversed equally the toxin loses action and the SNARE proteins are slowly regenerated past the afflicted prison cell.[one]

The seven toxin serotypes (A–Thou) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences.[58] [59] While the different toxin types all target members of the SNARE family, unlike toxin types target different SNARE family members.[55] The A, B, and E serotypes crusade homo botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months).[58] Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with the get-go letter indicating the lite chain type and the latter indicating the heavy chain type.[60] BoNT/FA received considerable attention under the proper noun "BoNT/H", every bit it was mistakenly thought it could not be neutralized past any existing antitoxin.[six]

Botulinum toxins are closely related to tetanus toxin; the two are collectively known as Clostridium neurotoxins and the light chain is classified by MEROPS equally family M27. Nonclassical types include BoNT/X (P0DPK1), which is toxic in mice and maybe in humans;[v] a BoNT/J (A0A242DI27) found in moo-cow Enterococcus;[61] and a BoNT/Wo (A0A069CUU9) constitute in the rice-colonizing Weissella oryzae.[60]

History [edit]

Initial descriptions and discovery of Clostridium botulinum [edit]

1 of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in the hamlet of Wildbad in what is now Baden-Württemberg, Frg. Xiii people became sick and vi died after eating pork tum filled with blood sausage, a local effeminateness. Additional cases of fatal food poisoning in Württemberg led the authorities to issue a public alert against consuming smoked blood sausages in 1802 and to collect instance reports of "sausage poisoning".[62] Betwixt 1817 and 1822, the German md Justinus Kerner published the offset consummate clarification of the symptoms of botulism, based on extensive clinical observations and animal experiments. He ended that the toxin develops in bad sausages under anaerobic conditions, is a biological substance, acts on the nervous system, and is lethal even in small amounts.[62] Kerner hypothesized that this "sausage toxin" could be used to care for a variety of diseases acquired past an overactive nervous arrangement, making him the outset to advise that it could exist used therapeutically.[63] In 1870, the High german physician Müller coined the term "botulism" to describe the disease acquired by sausage poisoning, from the Latin word botulus, meaning "sausage".[63]

In 1895 Émile van Ermengem, a Belgian microbiologist, discovered what is at present called Clostridium botulinum and confirmed that a toxin produced past the bacteria causes botulism.[64] On 14 December 1895, there was a large outbreak of botulism in the Belgian village of Ellezelles that occurred at a funeral where people ate pickled and smoked ham; 3 of them died. Past examining the contaminated ham and performing autopsies on the people who died after eating it, van Ermengem isolated an anaerobic microorganism that he called Bacillus botulinus.[62] He likewise performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from the bacteria. From these he concluded that the leaner themselves practise not cause foodborne botulism, but rather produce a toxin that causes the disease later it is ingested.[65] As a result of Kerner's and van Ermengem's research, it was thought that only contaminated meat or fish could cause botulism. This thought was refuted in 1904 when a botulism outbreak occurred in Darmstadt, Frg because of canned white beans. In 1910, the High german microbiologist J. Leuchs published a paper showing that the outbreaks in Ellezelles and Darmstadt were caused by different strains of Bacillus botulinus and that the toxins were serologically distinct.[62] In 1917, Bacillus botulinus was renamed Clostridium botulinum, as it was decided that term Bacillus should just refer to a grouping of aerobic microorganisms, while Clostridium would be only used to describe a group of anaerobic microorganisms.[64] In 1919, Georgina Shush used toxin-antitoxin reactions to identify two strains of Clostridium botulinum, which she designated A and B.[64]

Food canning [edit]

Over the next iii decades, 1895–1925, equally food canning was budgeted a billion-dollar-a-year manufacture, botulism was condign a public health hazard. Karl Friedrich Meyer, a Swiss-American veterinarian 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 product, and inactivating the toxin past heating. The California canning manufacture was thereby preserved.

Earth War Two [edit]

With the outbreak of Globe War 2, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff[66] developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army'due south Chemical Corps was disbanded, Schantz moved to the Food Research Found in Wisconsin, where he manufactured toxin for experimental use and 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-20th century,[67] and remains an important inquiry topic. Nearly all toxin treatments are based on this consequence in various body tissues.

Strabismus [edit]

Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, the electrical signal from an activated musculus, to guide injection) of local anesthetics equally a diagnostic technique for evaluating an individual muscle'due south contribution to an eye movement.[68] Considering strabismus surgery frequently needed repeating, a search was undertaken for not-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and serpent neurotoxins. Finally, inspired by Daniel B. Drachman'southward work with chicks at Johns Hopkins,[69] Alan B. Scott and colleagues injected botulinum toxin into monkey extraocular muscles.[70] 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 utilise, and began manufacturing botulinum blazon A neurotoxin in his San Francisco lab. He injected the beginning strabismus patients in 1977, reported its clinical utility in 1980,[71] and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("centre aligner").

In 1986, Oculinum Inc, Scott'southward micromanufacturer and benefactor 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 centre centers for their injections.[72]

Based on information from thousands of patients collected by 240 investigators, Oculinum Inc (which was soon acquired by Allergan) received FDA approving in 1989 to market Oculinum for clinical utilize in the United states to treat developed strabismus and blepharospasm. Allergan then began using the trademark Botox.[73] This original approval was granted under the 1983 U.s. Orphan Drug Deed.[74]

Cosmetics [edit]

The event of BTX-A on reducing and eliminating forehead wrinkles was first described and published past Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Dr. Clark was challenged with eliminating the disfigurement caused by simply the right side of the forehead muscles functioning after the left side of the brow was paralyzed during a facelift procedure. This patient had desired to wait amend from her facelift, merely was experiencing bizarre unilateral right forehead countenance height while the left countenance drooped, and she constantly demonstrated deep expressive right forehead wrinkles while the left side was perfectly shine due to the paralysis. Dr. Clark was aware that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal performance right forehead muscles to make both sides of the forehead appear the same. This study and case report of the Cosmetic use of Botulinum toxin to treat a Cosmetic complication of a Corrective surgery was the commencement study on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989.[75] Editors of the journal of the American Club of Plastic Surgeons have clearly stated "the start described apply of the toxin in artful circumstances was by Clark and Berris in 1989."[76]

Jean and Alastair 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). Alastair Carruthers reported that others at the time also noticed these effects and discussed the cosmetic potential of botulinum toxin.[77] Unlike other investigators, the Carruthers did more than just talk almost the possibility of using botulinum toxin cosmetically. They conducted a clinical study on otherwise normal individuals whose merely concern was their countenance furrow. They performed their written report during 1987-1989 and presented their results at the 1990 annual meeting of the American Society for Dermatologic Surgery. Their findings were subsequently published in 1992.[78]

Chronic pain [edit]

William J. Binder reported in 2000, that patients who had cosmetic injections around the face reported relief from chronic headache.[79] This was initially idea to be an indirect outcome of reduced musculus tension, but the toxin is now known to inhibit release of peripheral nociceptive neurotransmitters, suppressing the central pain processing systems responsible for migraine headache.[lxxx] [81]

Society and culture [edit]

Economics [edit]

As of 2018[update], botulinum toxin injections are the most common cosmetic operation, with 7.4 meg procedures in the United States, according to the American Society of Plastic Surgeons.[82] Qualifications for Botox injectors vary by county, state, and country. Botox corrective providers include dermatologists, plastic surgeons, aesthetic spa physicians, dentists, nurse practitioners, nurses, and dr. assistants.[ citation needed ]

The global marketplace for botulinum toxin products, driven past their corrective applications, was forecast to achieve $2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to accomplish $four.7 billion ($two billion in the U.S.) in the same timeframe.[83]

Global Market place
In 2019, 6,271,488 Botulinum Toxin procedures were administered worldwide.[84] The Global Botulinum Toxin market place size was US$4.83 billion in 2019 and is projected to reach US$7.71 billion by 2027.[84]
US Market
In 2020, 4,401,536 Botulinum Toxin Type A procedures were administered.[85] In 2019 the botulinum Toxin market place fabricated US$three.19 billion.[84]
Botox cost
Botox toll is generally determined by the number of units administered (avg. $ten.00 - $30.00 per unit) or by the surface area ($200–1000) and depends on expertise of a physician, clinic location, number of units, and treatment complication.
Insurance
Botox for medical purposes is unremarkably covered by insurance if deemed medically necessary past your doc and covers a plethora of medical problems including Overactive Bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in developed patients, cervical dystonia in adult patients, severe axillary hyperhidrosis (or other areas of the trunk), blepharospasm, upper or lower limb spasticity.[86] [87]
Pay per visit
In the United States and the majority of the developed world botox is usually not covered by major insurance carriers unless it's a function of sex activity reassignment surgery. Out-of-pocket botox cost is variable and depends on multiple factors including wrinkle severity, intervals between injections, physician'southward experience and many others.
Migraines
For migraine induced headaches the FDA-recommended dosage is 155 units and costs between $300 to $600 per treatment out of pocket when covered past insurance.[88]
Hyperhidrosis
Botox for excessive sweating is FDA approved.[45]
Cosmetic
Standard areas for aesthetics botox injections include facial and other areas that tin course fine lines and wrinkles due to every twenty-four hour period muscle contractions and/or facial expressions such every bit grinning, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows, horizontal lines on the forehead, crow'southward anxiety around the optics, and even circular bands that form effectually the neck secondary to platysmal hyperactivity.[89]

Bioterrorism [edit]

Botulinum toxin has been recognized as a potential agent for use in bioterrorism.[90] It can be absorbed through the eyes, mucous membranes, respiratory tract, and not-intact peel.[91] The effects of botulinum toxin are unlike from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are mostly much more rapid. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) volition increase mortality by enhancing botulinum toxin's machinery of toxicity.[92] With regard to detection, protocols using NBC detection equipment (such as One thousand-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested.[93] To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in expiry investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD50 units per milliliter accept been detected in poisoned patients.[94]

Japanese doomsday cult Aum Shinrikyo produced botulinum toxin and spread it as an aerosol in downtown Tokyo during the 1990s, merely the attacks caused no fatalities.[95]

During the early on 1980s, German and French newspapers reported that the law had raided a Baader-Meinhof gang prophylactic house in Paris and had found a makeshift laboratory that independent flasks full of Clostridium botulinum, which makes botulinum toxin. Their reports were later on establish to be wrong; no such lab was e'er found.[96]

Brand names [edit]

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

In the U.s.a., botulinum toxin products are manufactured by a variety of companies, for both therapeutic and corrective employ. A U.S. supplier reported in its visitor materials in 2011 that it could "supply the world's requirements for 25 indications approved past Government agencies around the globe" with less than 1 gram of raw botulinum toxin.[97] Myobloc or Neurobloc, a botulinum toxin type B production, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured past Galderma in the Britain, is licensed for the treatment of focal dystonias and certain cosmetic uses in the U.S. and other countries.[50]

Besides the three primary U.S. manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Deutschland by Merz, is also available for both therapeutic and cosmetic utilise in the U.S.[98] Lanzhou Constitute of Biological Products in China manufactures a BTX-A product; as of 2014, it was the just BTX-A canonical in Prc.[98] BTX-A is also sold as Lantox and Prosigne on the global market place.[99] Neuronox, a BTX-A product, was introduced by Medy-Tox Inc. of South Korea in 2009;[100]

Toxin production [edit]

Botulism toxins are produced past bacteria of the genus Clostridium, namely C. botulinum, C. butyricum, C. baratii and C. argentinense, [101] which are widely distributed, including in soil and grit. Besides, the bacteria can be found within homes on floors, carpet, and countertops fifty-fifty after cleaning.[102] Food-borne botulism results, indirectly, from ingestion of food contaminated with Clostridium spores, where exposure to an anaerobic surround allows the spores to germinate, afterward which the bacteria can multiply and produce toxin.[102] Critically, ingestion of toxin rather than spores or vegetative bacteria causes botulism.[102] Botulism is all the same known to exist transmitted through canned foods not cooked correctly earlier canning or afterward can opening, then is preventable.[102] Babe botulism arising from consumption of honey or any other food that can carry these spores tin can exist prevented by eliminating these foods from diets of children less than 12 months old.[103]

Organism and toxin susceptibilities [edit]

Proper refrigeration at temperatures below 3 °C (38 °F) retards the growth of C. botulinum. The organism is also susceptible to high salt, high oxygen, and depression pH levels.[10] The toxin itself is rapidly destroyed by estrus, such as in thorough cooking.[104] The spores that produce the toxin are heat-tolerant and will survive boiling h2o for an extended period of time.[105]

The botulinum toxin is denatured and thus deactivated at temperatures greater than 85 °C (185 °F) for five minutes.[106] As a zinc metalloprotease (see below), the toxin's activeness is too susceptible, post-exposure, to inhibition by protease inhibitors, east.1000., zinc-analogous hydroxamates.[58] [107]

Research [edit]

Blepharospasm and strabismus [edit]

University-based ophthalmologists in the United states and Canada farther refined the apply of botulinum toxin as a therapeutic amanuensis. By 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of blepharospasm and strabismus.[108] Side furnishings in treatment of this status were deemed to be rare, mild and treatable.[109] The benign furnishings of the injection lasted but 4–6 months. Thus, blepharospasm patients required re-injection ii or 3 times a yr.[ citation needed ]

In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug considering of an disability to obtain product liability insurance. Patients became drastic, 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 iv months, American blepharospasm patients had to arrange to have their injections performed past participating doctors at Canadian heart centers until the liability issues could be resolved.[72]

In Dec 1989, Botox was canonical by the U.S. FDA for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients over 12 years old.[73]

Botox has not been approved for any pediatric utilise.[fifty] Information technology 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.[50] In the case of handling of infantile esotropia in patients younger than 12 years of age, several studies have yielded differing results.[37] [ better source needed ]

Cosmetic [edit]

The effect of BTX-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, Doctor a plastic surgeon from Sacramento, California. In 1987 Dr. Clark was challenged with eliminating the disfigurement caused past only the right side of the forehead muscles functioning afterwards the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look ameliorate from her facelift, but was experiencing bizarre unilateral right brow countenance acme while the left eyebrow drooped and she emoted with deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Dr. Clark was aware that Botulinum toxin was safely beingness used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal performance right forehead muscles to brand both sides of the forehead appear the same. This study and case study of the Cosmetic utilize of Botulinum toxin to treat a Cosmetic complication of a Cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the periodical Plastic and Reconstructive Surgery in 1989.[75][76] Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the offset described use of the toxin in aesthetic circumstances was past Clark and Berris in 1989."[76]

JD and JA Carruthers too studied and reported in 1992 the apply of BTX-A as a cosmetic treatment.[78] They conducted a study of patients whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of 17 patients available for follow-up demonstrated a cosmetic improvement. This report was reported at a meeting in 1991. The study for the treatment of glabellar pout lines was published in 1992.[78] This upshot was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen.[110]). The FDA appear regulatory approval of botulinum toxin type A (Botox Corrective) to temporarily improve the appearance of moderate-to-astringent frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials.[111] Well earlier this, the cosmetic use of botulinum toxin type A became widespread.[112] The results of Botox Corrective can last up to four months and may vary with each patient.[113] The U.S. Food and Drug Administration (FDA) approved an alternative product-rubber testing method in response to increasing public business organization that LD50 testing was required for each batch sold in the market.[114] [115]

BTX-A has also been used in the handling of gummy smiles,[116] the cloth is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward motion of lip thus resulting in a smile with a less exposure of gingiva.[117] Botox is usually injected in the iii lip lift muscles that converge on the lateral side of the ala of the olfactory organ; the levator labii superioris (LLS), the levator labii superioris alaeque nasi muscle (LLSAN), and the zygomaticus minor (ZMi).[118] [119]

Upper motor neuron syndrome [edit]

BTX-A is now a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such every bit cerebral palsy,[7] for muscles with an impaired ability to effectively lengthen. Muscles afflicted by UMNS frequently are limited by weakness, loss of reciprocal inhibition, decreased move control, and hypertonicity (including spasticity). In January 2014, Botulinum toxin was canonical by United kingdom of great britain and northern ireland's Medicines and Healthcare products Regulatory Bureau (MHRA) for the treatment of talocrural joint inability due to lower limb spasticity associated with stroke in adults.[31] Joint motion may be restricted by severe muscle imbalance related to the syndrome, when some muscles are markedly hypertonic, and lack constructive active lengthening. Injecting an overactive muscle to decrease its level of contraction tin allow improved reciprocal motion, so improved power to move and exercise.[7]

Sialorrhea [edit]

Sialorrhea is a condition where oral secretions are unable to be eliminated, causing pooling of saliva in the mouth. This condition can exist acquired by various neurological syndromes such as Bell's palsy, mental retardation, and cognitive palsy. Injection of BTX-A into salivary glands is useful in reducing the secretions.[120]

Cervical dystonia [edit]

BTX-A is commonly used to care for cervical dystonia, but it can go ineffective afterward a time. Botulinum toxin blazon B (BTX-B) received FDA blessing for handling of cervical dystonia on 21 December 2000. Trade names for BTX-B are Myobloc in the United States, and Neurobloc in the European Spousal relationship.[98]

Chronic migraine [edit]

Onabotulinumtoxin A (trade proper noun Botox) received FDA approving for treatment of chronic migraines on 15 Oct 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 handling.[121] [122]

Since and 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[123] who showroom headache characteristics consistent with: pressure perceived from exterior source, shorter total duration of chronic migraines (<xxx years), "detoxification" of patients with coexisting chronic daily headache due to medication overuse, and no electric current history of other preventive headache medications.[124]

Depression [edit]

A few modest trials have found benefits in people with depression.[125] [126] Enquiry is based on the facial feedback hypothesis.[127]

Premature ejaculation [edit]

The drug for the treatment of premature ejaculation has been under evolution since August 7, 2013, and is in Phase II of the FDA trials.[126] [128]

References [edit]

  1. ^ a b c d e f grand Montecucco C, Molgó J (June 2005). "Botulinal neurotoxins: revival of an sometime killer". Current Opinion in Pharmacology. five (3): 274–279. doi:10.1016/j.coph.2004.12.006. PMID 15907915.
  2. ^ Figgitt DP, Noble S (2002). "Botulinum toxin B: a review of its therapeutic potential in the management of cervical dystonia". Drugs. 62 (iv): 705–722. doi:10.2165/00003495-200262040-00011. PMID 11893235. S2CID 46981635.
  3. ^ Janes LE, Connor LM, Moradi A, Alghoul M (April 2021). "Current Utilize of Corrective Toxins to Meliorate Facial Aesthetics". Plastic and Reconstructive Surgery. 147 (4): 644e–657e. doi:10.1097/PRS.0000000000007762. PMID 33776040. S2CID 232408799.
  4. ^ Rosales RL, Bigalke H, Dressler D (February 2006). "Pharmacology of botulinum toxin: differences betwixt blazon A preparations". European Journal of Neurology. thirteen (Suppl ane): 2–10. doi:x.1111/j.1468-1331.2006.01438.x. PMID 16417591. S2CID 32387953.
  5. ^ a b "Botulism toxin X: Time to update the textbooks, thanks to genomic sequencing". Boston Children'southward Hospital. 7 August 2017. Retrieved 28 October 2019.
  6. ^ a b c "Study: Novel botulinum toxin less dangerous than thought". CIDRAP. Academy of Minnesota. 17 June 2015. Retrieved 28 October 2019.
  7. ^ a b c d e f Farag SM, Mohammed MO, El-Sobky TA, ElKadery NA, ElZohiery AK (March 2020). "Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials". JBJS Reviews. eight (3): e0119. doi:10.2106/JBJS.RVW.19.00119. PMC7161716. PMID 32224633.
  8. ^ a b c d Blumetti FC, Belloti JC, Tamaoki MJ, Pinto JA (Oct 2019). "Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy". The Cochrane Database of Systematic Reviews. 2019 (10): CD001408. doi:x.1002/14651858.CD001408.pub2. PMC6779591. PMID 31591703.
  9. ^ American Society of Health-System Pharmacists (27 Oct 2011). "OnabotulinumtoxinA (Botulinum Toxin Type A) Monograph for Professionals". drugs.com . Retrieved iv March 2015.
  10. ^ a b c "Botulism: Cardinal facts". Earth Health Organisation.
  11. ^ Košenina Due south, Masuyer G, Zhang Due south, Dong M, Stenmark P (June 2019). "Crystal construction of the catalytic domain of the Weissella oryzae botulinum-like toxin". FEBS Letters. 593 (12): 1403–1410. doi:10.1002/1873-3468.13446. PMID 31111466.
  12. ^ Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. (February 2001). "Botulinum toxin as a biological weapon: medical and public health management". JAMA. 285 (8): 1059–1070. doi:10.1001/jama.285.8.1059. PMID 11209178.
  13. ^ "Drug Approving Package: Dysport (abobotulinumtoxin) NDA #125274s000". U.S. Food and Drug Administration (FDA). 17 August 2011. Retrieved 23 November 2019.
  14. ^ "Drug Approval Packet: Brand Name (Generic Name) NDA #". accessdata.fda.gov. 24 December 1999. Retrieved 23 Nov 2019.
  15. ^ "Drug Approval Package: Jeuveau". U.S. Nutrient and Drug Administration (FDA). five March 2019. Archived from the original on 23 November 2019. Retrieved 22 November 2019. Public Domain This article incorporates text from this source, which is in the public domain .
  16. ^ a b Krause R (10 June 2019). "Jeuveau, The Near Affordable Contraction Injectable". refinery29.com.
  17. ^ Ozcakir Due south, Sivrioglu K (June 2007). "Botulinum toxin in poststroke spasticity". Clinical Medicine & Research. 5 (2): 132–138. doi:10.3121/cmr.2007.716. PMC1905930. PMID 17607049.
  18. ^ Yan X, Lan J, Liu Y, Miao J (November 2018). "Efficacy and Safe of Botulinum Toxin Type A in Spasticity Caused past Spinal Cord Injury: A Randomized, Controlled Trial". Medical Scientific discipline Monitor. 24: 8160–8171. doi:10.12659/MSM.911296. PMC6243868. PMID 30423587.
  19. ^ "Cervical dystonia - Symptoms and causes". Mayo Clinic. 28 Jan 2014. Retrieved xiv October 2015.
  20. ^ a b Shukla HD, Sharma SK (2005). "Clostridium botulinum: a problems with beauty and weapon". Disquisitional Reviews in Microbiology. 31 (1): eleven–18. doi:ten.1080/10408410590912952. PMID 15839401. S2CID 2855356.
  21. ^ Pacik PT (December 2009). "Botox treatment for vaginismus". Plastic and Reconstructive Surgery. 124 (6): 455e–456e. doi:x.1097/PRS.0b013e3181bf7f11. PMID 19952618.
  22. ^ a b c d Felber ES (October 2006). "Botulinum toxin in primary care medicine". The Journal of the American Osteopathic Clan. 106 (10): 609–614. doi:10.7556/jaoa. PMID 17122031.
  23. ^ Stavropoulos SN, Friedel D, Modayil R, Iqbal Due south, Grendell JH (March 2013). "Endoscopic approaches to treatment of achalasia". Therapeutic Advances in Gastroenterology. six (ii): 115–135. doi:10.1177/1756283X12468039. PMC3589133. PMID 23503707.
  24. ^ Long H, Liao Z, Wang Y, Liao Fifty, Lai W (February 2012). "Efficacy of botulinum toxins on bruxism: an evidence-based review". International Dental Journal. 62 (i): i–5. doi:10.1111/j.1875-595X.2011.00085.ten. PMID 22251031.
  25. ^ Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, et al. (October 2011). "Contemporary management of lower urinary tract illness with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)". European Urology. 60 (4): 784–795. doi:x.1016/j.eururo.2011.07.001. PMID 21782318.
  26. ^ Villalba H, Villalba S, Abbas MA (2007). "Anal scissure: a common cause of anal pain". The Permanente Periodical. eleven (4): 62–65. doi:10.7812/tpp/07-072. PMC3048443. PMID 21412485.
  27. ^ Duthie JB, Vincent 1000, Herbison GP, Wilson DI, Wilson D (December 2011). Duthie JB (ed.). "Botulinum toxin injections for adults with overactive float syndrome". The Cochrane Database of Systematic Reviews (12): CD005493. doi:10.1002/14651858.CD005493.pub3. PMID 22161392.
  28. ^ Scott AB (1994). "Change of eye muscle sarcomeres according to eye position". Journal of Pediatric Ophthalmology and Strabismus. 31 (two): 85–88. doi:10.3928/0191-3913-19940301-05. PMID 8014792.
  29. ^ Simpson Fifty (2 Dec 2012). Botulinum Neurotoxin and Tetanus Toxin. Elsevier. ISBN978-0-323-14160-iv.
  30. ^ "Could my child'south crossed eye be corrected with Botox? - Boston Children's Infirmary". Thriving Blog. 14 April 2017. Archived from the original on 25 January 2021. Retrieved 13 March 2020.
  31. ^ a b UK Approves New Botox Utilize Archived 22 Feb 2014 at the Wayback Automobile. dddmag.com. iv February 2014
  32. ^ "United kingdom of great britain and northern ireland'south MHRA approves Botox for treatment of ankle inability in stroke survivors". world wide web.thepharmaletter.com . Retrieved 16 March 2020.
  33. ^ "FDA Approved Drug Products – Dysport". U.S. Nutrient and Drug Administration (FDA). Archived from the original on eight November 2016. Retrieved vii November 2016. Public Domain This commodity incorporates text from this source, which is in the public domain .
  34. ^ Pavone 5, Testa G, Restivo DA, Cannavò L, Condorelli Thou, Portinaro NM, Sessa G (xix February 2016). "Botulinum Toxin Treatment for Limb Spasticity in Babyhood Cerebral Palsy". Frontiers in Pharmacology. 7: 29. doi:10.3389/fphar.2016.00029. PMC4759702. PMID 26924985.
  35. ^ Syed YY (August 2017). "AbobotulinumtoxinA: A Review in Pediatric Lower Limb Spasticity". Paediatric Drugs. 19 (4): 367–373. doi:ten.1007/s40272-017-0242-4. PMID 28623614. S2CID 24857218.
  36. ^ Wittich CM, Burkle CM, Lanier WL (October 2012). "Ten common questions (and their answers) almost off-label drug apply". Mayo Clinic Proceedings. 87 (x): 982–990. doi:10.1016/j.mayocp.2012.04.017. PMC3538391. PMID 22877654.
  37. ^ a b Ocampo VV, Foster CS (30 May 2012). "Infantile Esotropia Handling & Management". Medscape. Retrieved 6 April 2014.
  38. ^ a b Eisenach JH, Atkinson JL, Fealey RD (May 2005). "Hyperhidrosis: evolving therapies for a well-established phenomenon". Mayo Clinic Proceedings. 80 (5): 657–666. doi:10.4065/80.5.657. PMID 15887434.
  39. ^ "FDA Approves Botox to Treat Chronic Migraines". WebMD . Retrieved 12 May 2017.
  40. ^ Satriyasa, Bagus Komang (10 April 2019). "Botulinum toxin (Botox) A for reducing the appearance of facial wrinkles: a literature review of clinical use and pharmacological aspect". Clinical, Cosmetic and Investigational Dermatology. 12: 223–228. doi:10.2147/CCID.S202919. ISSN 1178-7015. PMC6489637. PMID 31114283.
  41. ^ a b c d e Modest R (August 2014). "Botulinum toxin injection for facial wrinkles". American Family Physician. xc (3): 168–175. PMID 25077722.
  42. ^ Mittal And then, Safarpour D, Jabbari B (Feb 2016). "Botulinum Toxin Handling of Neuropathic Pain". Seminars in Neurology. 36 (ane): 73–83. doi:10.1055/southward-0036-1571953. PMID 26866499.
  43. ^ Charles PD (November 2004). "Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses". American Journal of Health-System Pharmacy. 61 (22 Suppl vi): S11–S23. doi:ten.1093/ajhp/61.suppl_6.S11. PMID 15598005.
  44. ^ Singh JA, Fitzgerald PM (September 2010). "Botulinum toxin for shoulder pain". The Cochrane Database of Systematic Reviews (9): CD008271. doi:10.1002/14651858.cd008271.pub2. PMID 20824874.
  45. ^ a b Nigam PK, Nigam A (2010). "Botulinum toxin". Indian Periodical of Dermatology. 55 (1): viii–14. doi:10.4103/0019-5154.60343. PMC2856357. PMID 20418969.
  46. ^ a b c d Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM (September 2005). "Botulinum toxin blazon A injections: agin events reported to the U.s. Nutrient and Drug Administration in therapeutic and cosmetic cases". Periodical of the American University of Dermatology. 53 (3): 407–415. doi:10.1016/j.jaad.2005.06.011. PMID 16112345.
  47. ^ Schiffer, Jessica (8 April 2021). "How Barely-There Botox Became the Norm". The New York Times. ISSN 0362-4331. Archived from the original on 28 December 2021. Retrieved 23 November 2021.
  48. ^ "FDA Notifies Public of Adverse Reactions Linked to Botox Utilise". U.S. Food and Drug Administration (FDA). viii February 2008. Archived from the original on 2 March 2012. Retrieved six May 2012. Public Domain This commodity incorporates text from this source, which is in the public domain .
  49. ^ a b "FDA Gives Update on Botulinum Toxin Safety Warnings; Established Names of Drugs Changed". Pharmaceutical Online. four August 2009. Retrieved 16 July 2019.
  50. ^ a b c d "Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed equally Myobloc)". U.S. Nutrient and Drug Administration (FDA). 13 September 2015. Archived from the original on thirteen September 2015. Retrieved ane September 2015. Public Domain This article incorporates text from this source, which is in the public domain .
  51. ^ "Botox chemic may spread, Health Canada confirms". CBC News. xiii January 2009. Archived from the original on 21 February 2009.
  52. ^ "Kinds of Botulism". Centers for Illness Command and Prevention. Retrieved 4 October 2016.
  53. ^ a b c d "Botulism – Diagnosis and Treatment". Centers for Disease Control and Prevention. Retrieved 5 October 2016.
  54. ^ Barash JR, Arnon SS (January 2014). "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. PMID 24106296.
  55. ^ a b Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, et al. (October 2005). "Botulinum neurotoxin detection and differentiation by mass spectrometry". Emerging Infectious Diseases. 11 (x): 1578–1583. doi:10.3201/eid1110.041279. PMC3366733. PMID 16318699.
  56. ^ a b Dressler D, Saberi FA, Barbosa ER (March 2005). "Botulinum toxin: mechanisms of activity". Arquivos de Neuro-Psiquiatria. 63 (1): 180–185. doi:x.1159/000083259. PMID 15830090. S2CID 16307223.
  57. ^ Dong, Min; Masuyer, Geoffrey; Stenmark, Pål (20 June 2019). "Botulinum and Tetanus Neurotoxins". Annual Review of Biochemistry. 88 (1): 811–837. doi:ten.1146/annurev-biochem-013118-111654. PMC7539302. PMID 30388027.
  58. ^ a b c d e Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL (Dec 2010). "Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication". Molecules. 16 (1): 202–220. doi:10.3390/molecules16010202. PMC6259422. PMID 21193845.
  59. ^ Loma KK, Smith TJ (2013). Rummel A, Binz T (eds.). "Genetic diversity inside Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes". Electric current Topics in Microbiology and Immunology. Springer. 364: i–20. doi:ten.1007/978-three-642-33570-9_1. ISBN978-3-642-33569-three. PMID 23239346.
  60. ^ a b Davies, Jonathan; Liu, Sai; Acharya, K. (20 October 2018). "Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics". Toxins. x (x): 421. doi:10.3390/toxins10100421. PMC6215321. PMID 30347838.
  61. ^ Brunt J, Carter AT, Stringer SC, Peck MW (February 2018). "Identification of a novel botulinum neurotoxin gene cluster in Enterococcus". FEBS Letters. 592 (3): 310–317. doi:10.1002/1873-3468.12969. PMC5838542. PMID 29323697.
  62. ^ a b c d Erbguth FJ (March 2004). "Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin". Motion Disorders. 19 (Supplement viii): S2–S6. doi:ten.1002/mds.20003. PMID 15027048. S2CID 8190807.
  63. ^ a b Erbguth FJ, Naumann Chiliad (November 1999). "Historical aspects of botulinum toxin: Justinus Kerner (1786-1862) and the "sausage poison"". Neurology. 53 (8): 1850–1853. doi:10.1212/wnl.53.8.1850. PMID 10563638. S2CID 46559225.
  64. ^ a b c Monheit GD, Pickett A (May 2017). "AbobotulinumtoxinA: A 25-Year History". Aesthetic Surgery Journal. 37 (suppl_1): S4–S11. doi:10.1093/asj/sjw284. PMC5434488. PMID 28388718.
  65. ^ Pellett S (June 2012). "Learning from the past: historical aspects of bacterial toxins as pharmaceuticals". Current Opinion in Microbiology. 15 (3): 292–299. doi:10.1016/j.mib.2012.05.005. PMID 22651975.
  66. ^ Lamanna C, McELROY OE, Eklund HW (May 1946). "The purification and crystallization of Clostridium botulinum type A toxin". Science. 103 (2681): 613–614. Bibcode:1946Sci...103..613L. doi:ten.1126/science.103.2681.613. PMID 21026141.
  67. ^ Burgen Equally, Dickens F, Zatman LJ (August 1949). "The action of botulinum toxin on the neuro-muscular junction". The Journal of Physiology. 109 (ane–2): x–24. doi:10.1113/jphysiol.1949.sp004364. PMC1392572. PMID 15394302.
  68. ^ Magoon Due east, Cruciger M, Scott AB, Jampolsky A (May 1982). "Diagnostic injection of Xylocaine into extraocular muscles". Ophthalmology. 89 (five): 489–491. doi:10.1016/s0161-6420(82)34764-viii. PMID 7099568.
  69. ^ Drachman DB (August 1964). "Atrophy of Skeletal Musculus in Chick Embryos Treated with Botulinum Toxin". Science. 145 (3633): 719–721. Bibcode:1964Sci...145..719D. doi:10.1126/science.145.3633.719. PMID 14163805. S2CID 43093912.
  70. ^ Scott AB, Rosenbaum A, Collins CC (December 1973). "Pharmacologic weakening of extraocular muscles". Investigative Ophthalmology. 12 (12): 924–927. PMID 4203467.
  71. ^ Scott AB (October 1980). "Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery". Ophthalmology. 87 (ten): 1044–1049. doi:ten.1016/s0161-6420(lxxx)35127-0. PMID 7243198.
  72. ^ a b Boffey PM (14 October 1986). "Loss Of Drug Relegates Many To Blindness Again". The New York Times . Retrieved 14 July 2010.
  73. ^ a b United States Department of Wellness and Homo Services (xxx April 2009). "Re: Docket No. FDA-2008-P-0061" (PDF). U.S. Nutrient and Drug Assistants (FDA). Archived from the original (PDF) on vi July 2010. Retrieved 26 July 2010. Public Domain This article incorporates text from this source, which is in the public domain .
  74. ^ Wellman-Labadie O, Zhou Y (May 2010). "The United states of america Orphan Drug Act: rare disease research stimulator or commercial opportunity?". Wellness Policy. 95 (ii–3): 216–228. doi:10.1016/j.healthpol.2009.12.001. PMID 20036435.
  75. ^ a b Clark RP, Berris CE (Baronial 1989). "Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis". Plastic and Reconstructive Surgery. 84 (2): 353–355. doi:x.1097/01.prs.0000205566.47797.8d. PMID 2748749.
  76. ^ a b Rohrich, Rod J.; Janis, Jeffrey E.; Fagien, Steven; Stuzin, James 1000. (October 2003). "The Cosmetic Use of Botulinum Toxin". Plastic and Reconstructive Surgery. 112 (Supplement): 177S–188S. doi:10.1097/01.prs.0000082208.37239.5b. ISSN 0032-1052. PMID 14504502.
  77. ^ Carruthers A (November–December 2003). "History of the clinical utilise of botulinum toxin A and B". Clinics in Dermatology. 21 (6): 469–472. doi:10.1016/j.clindermatol.2003.xi.003. PMID 14759577.
  78. ^ 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:x.1111/j.1524-4725.1992.tb03295.10. PMID 1740562.
  79. ^ Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM (December 2000). "Botulinum toxin blazon A (BOTOX) for treatment of migraine headaches: an open-label study". Otolaryngology–Head and Neck Surgery. 123 (6): 669–676. doi:10.1067/mhn.2000.110960. PMID 11112955. S2CID 24406607.
  80. ^ Jackson JL, Kuriyama A, Hayashino Y (April 2012). "Botulinum toxin A for prophylactic handling of migraine and tension headaches in adults: a meta-assay". JAMA. 307 (16): 1736–1745. doi:10.1001/jama.2012.505. PMID 22535858.
  81. ^ Ramachandran R, Yaksh TL (September 2014). "Therapeutic employ of botulinum toxin in migraine: mechanisms of action". British Periodical of Pharmacology. 171 (18): 4177–4192. doi:x.1111/bph.12763. PMC4241086. PMID 24819339.
  82. ^ "New plastic surgery statistics reveal trends toward torso enhancement". Plastic Surgery. eleven March 2019. Archived from the original on 12 March 2019.
  83. ^ Chapman L (ten May 2012). "The global botox market forecast to reach $2.nine billion past 2018". Archived from the original on half-dozen August 2012. Retrieved 5 Oct 2012.
  84. ^ a b c "Botulinum Toxin Market". Fortune Business Insights.
  85. ^ "2020 National Plastic Surgery Statistics: Cosmetic Surgical Procedures" (PDF). American Social club of Plastic Surgeons.
  86. ^ "Medicare Guidelines for Botox Treatments". MedicareFAQ.com. 27 September 2021.
  87. ^ "BOTOX (onabotulinumtoxinA) for injection, for intramuscular, intradetrusor, or intradermal use" (PDF). Highlights of Prescribing Information. United States Food and Drug Assistants.
  88. ^ "Botox for Migraine". The American Migraine Foundation.
  89. ^ "BOTOX® Procedures: What is BOTOX® & How Does it Work". The American University of Facial Esthetics.
  90. ^ Koirala J, Basnet South (14 July 2004). "Botulism, Botulinum Toxin, and Bioterrorism: Review and Update". Medscape. Cliggott Publishing. Archived from the original on 1 June 2011. Retrieved fourteen July 2010.
  91. ^ Public Wellness Bureau of Canada (19 Apr 2011). "Pathogen Safety Information Sheets: Infectious Substances – Clostridium botulinum".
  92. ^ Fleisher LA, Roizen MF, Roizen J (31 May 2017). Essence of Anesthesia Practice E-Volume. Elsevier Health Sciences. ISBN978-0-323-39541-0.
  93. ^ "M8 Paper" (PDF). www.wmddetectorselector.army.mil. U.S. Army. Retrieved xvi September 2020. M8 newspaper is a chemically-treated, dye-impregnated paper used to detect liquid substances for the presence of V- and 1000-blazon nerve agents and H- and L-blazon blister agents.
  94. ^ Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Ca.: Biomedical Publications. pp. 260–61. ISBN978-0-9626523-nine-4.
  95. ^ Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. (Working Grouping on Civilian Biodefense) (Feb 2001). "Botulinum toxin every bit a biological weapon: medical and public health direction". JAMA. 285 (8): 1059–1070. doi:10.1001/jama.285.8.1059. PMID 11209178.
  96. ^ McAdams D, Kornblet S (2011). "Baader-Meinhof Group (OR Baader-Meinhof Gang". In Pilch RF, Zilinskas RA (eds.). Encyclopedia of Bioterrorism Defense force. Wiley-Liss. doi:10.1002/0471686786.ebd0012.pub2. ISBN978-0-471-68678-1.
  97. ^ "2011 Allergan Annual Report" (PDF). Allergan. Retrieved 3 May 2012. Run across PDF p. 7.
  98. ^ a b c Walker TJ, Dayan SH (February 2014). "Comparing and overview of currently available neurotoxins". The Journal of Clinical and Aesthetic Dermatology. 7 (ii): 31–39. PMC3935649. PMID 24587850.
  99. ^ "Botulinum Toxin Type A". Hugh Source (International) Limited. Retrieved xiv July 2010.
  100. ^ Petrou I (Jump 2009). "Medy-Tox Introduces Neuronox to the Botulinum Toxin Arena" (PDF). The European Aesthetic Guide. Archived from the original (PDF) on xx March 2013. Retrieved 9 December 2009.
  101. ^ Schantz EJ, Johnson EA (March 1992). "Backdrop and use of botulinum toxin and other microbial neurotoxins in medicine". Microbiological Reviews. 56 (1): 80–99. doi:10.1128/MMBR.56.1.fourscore-99.1992. PMC372855. PMID 1579114.
  102. ^ a b c d "Nigh Botulism | Botulism | CDC". world wide web.cdc.gov. ix Oct 2018. Retrieved 13 May 2020.
  103. ^ "Botulism". Centers for Disease Command and Prevention (CDC). 19 Baronial 2019. Retrieved 28 August 2019.
  104. ^ Licciardello JJ, Nickerson JT, Ribich CA, Goldblith SA (March 1967). "Thermal inactivation of blazon E botulinum toxin". Applied Microbiology. 15 (2): 249–256. doi:10.1128/AEM.xv.two.249-256.1967. PMC546888. PMID 5339838.
  105. ^ Setlow P (April 2007). "I will survive: DNA protection in bacterial spores". Trends in Microbiology. 15 (4): 172–180. doi:x.1016/j.tim.2007.02.004. PMID 17336071.
  106. ^ "Fact sheets - Botulism". Globe Health Organization. 10 January 2018. Retrieved 23 March 2019.
  107. ^ Capková 1000, Salzameda NT, Janda KD (October 2009). "Investigations into pocket-size molecule not-peptidic inhibitors of the botulinum neurotoxins". Toxicon. 54 (5): 575–582. doi:10.1016/j.toxicon.2009.03.016. PMC2730986. PMID 19327377.
  108. ^ Flanders M, Tischler A, Wise J, Williams F, Beneish R, Auger Due north (June 1987). "Injection of type A botulinum toxin into extraocular muscles for correction of strabismus". Canadian Journal of Ophthalmology. 22 (4): 212–217. PMID 3607594.
  109. ^ "Botulinum toxin therapy of eye muscle disorders. Safety and effectiveness. American Academy of Ophthalmology". Ophthalmology. 96 (Suppl 37-41): 37–41. September 1989. doi:10.1016/s0161-6420(89)32989-seven. PMID 2779991.
  110. ^ 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): 141–146. doi:10.1055/s-2008-1064563. PMID 7995530.
  111. ^ "Botulinum Toxin Blazon A Product Blessing Data – Licensing Action 4/12/02". U.Due south. Food and Drug Assistants (FDA). 29 Oct 2009. Archived from the original on eight March 2010. Retrieved 26 July 2010. Public Domain This article incorporates text from this source, which is in the public domain .
  112. ^ Giesler M (2012). "How Doppelgänger Brand Images Influence the Market Creation Process: Longitudinal Insights from the Rising of Botox Cosmetic". Periodical of Marketing. 76 (vi): 55–68. doi:10.1509/jm.10.0406. S2CID 167319134.
  113. ^ "Botox Cosmetic (onabotulinumtoxinA) Product Information". Allergan. 22 January 2014.
  114. ^ "Allergan Receives FDA Approval for First-of-Its-Kind, Fully in vitro, Cell-Based Analysis for Botox and Botox Cosmetic (onabotulinumtoxinA)". Allergan. 24 June 2011. Archived from the original on 26 June 2011. Retrieved 26 June 2011.
  115. ^ "In U.South., Few Alternatives To Testing On Animals". The Washington Post. 12 April 2008. Retrieved 26 June 2011.
  116. ^ Nayyar P, Kumar P, Nayyar PV, Singh A (December 2014). "BOTOX: Broadening the Horizon of Dentistry". Journal of Clinical and Diagnostic Research. 8 (12): ZE25–ZE29. doi:10.7860/JCDR/2014/11624.5341. PMC4316364. PMID 25654058.
  117. ^ Hwang WS, Hur MS, Hu KS, Song WC, Koh KS, Baik HS, et al. (Jan 2009). "Surface anatomy of the lip lift muscles for the treatment of viscous smile using botulinum toxin". The Angle Orthodontist. 79 (1): lxx–77. doi:ten.2319/091407-437.1. PMID 19123705.
  118. ^ Gracco A, Tracey S (May 2010). "Botox and the viscid smiling". Progress in Orthodontics. eleven (one): 76–82. doi:ten.1016/j.pio.2010.04.004. PMID 20529632.
  119. ^ Mazzuco R, Hexsel D (December 2010). "Gummy smile and botulinum toxin: a new arroyo based on the gingival exposure area". Journal of the American Academy of Dermatology. 63 (6): 1042–1051. doi:10.1016/j.jaad.2010.02.053. PMID 21093661.
  120. ^ Khan WU, Campisi P, Nadarajah Southward, Shakur YA, Khan N, Semenuk D, et al. (April 2011). "Botulinum toxin A for treatment of sialorrhea in children: an effective, minimally invasive arroyo". Archives of Otolaryngology–Head & Neck Surgery. 137 (4): 339–344. doi:10.1001/archoto.2010.240. PMID 21242533.
  121. ^ "FDA approves Botox to treat chronic migraine". U.S. Food and Drug Administration (FDA) (Press release). 19 October 2010. Archived from the original on xix Oct 2010. Retrieved 23 November 2019. Public Domain This commodity incorporates text from this source, which is in the public domain .
  122. ^ Watkins T (15 October 2010). "FDA approves Botox as migraine preventative". CNN.
  123. ^ Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, et al. (June 2010). "OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program". Headache. l (6): 921–936. doi:x.1111/j.1526-4610.2010.01678.x. PMID 20487038. S2CID 9621285.
  124. ^ Ashkenazi A (March 2010). "Botulinum toxin type a for chronic migraine". Current Neurology and Neuroscience Reports. 10 (2): 140–146. doi:10.1007/s11910-010-0087-5. PMID 20425239. S2CID 32191932.
  125. ^ 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–119S. doi:10.1097/PRS.0000000000001733. PMID 26441090. S2CID 24196194.
  126. ^ a b "Onabotulinum toxin A - Allergan - AdisInsight".
  127. ^ Finzi Eastward, Rosenthal NE (May 2014). "Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial". Periodical of Psychiatric Inquiry. 52: 1–vi. doi:ten.1016/j.jpsychires.2013.11.006. PMID 24345483.
  128. ^ Allergan (21 September 2018). "An Exploratory Report of the Safe and Efficacy of Botox for the Treatment of Premature Ejaculation".

External links [edit]

  • A Poison That Tin can Heal from the U.Due south. Food and Drug Administration (FDA)
  • BotDB: all-encompassing resources on BoNT structures, inhibitors, kinetics, and literature
  • A consumer sociological investigation of Botox Cosmetic's Rise
  • Overview of all the structural information bachelor in the PDB for UniProt: P0DPI1 (Botulinum neurotoxin blazon A) at the PDBe-KB.
  • Overview of all the structural information bachelor in the PDB for UniProt: P10844 (Botulinum neurotoxin blazon B) at the PDBe-KB.
  • Overview of all the structural information bachelor in the PDB for UniProt: A0A0X1KH89 (Bontoxilysin A) at the PDBe-KB.
  • "OnabotulinumtoxinA". Drug Information Portal. U.S. National Library of Medicine.
  • "RimabotulinumtoxinB". Drug Data Portal. U.Due south. National Library of Medicine.
  • "AbobotulinumtoxinA". Drug Information Portal. U.S. National Library of Medicine.
  • "Botox prescribing information". DailyMed.
  • "Myobloc- rimabotulinumtoxinb injection, solution label prescribing data". DailyMed.
  • "Dysport prescribing data". DailyMed.
  • "AbobotulinumtoxinA Injection". MedlinePlus.
  • "IncobotulinumtoxinA Injection". MedlinePlus.
  • "OnabotulinumtoxinA Injection". MedlinePlus.
  • "PrabotulinumtoxinA-xvfs Injection". MedlinePlus.
  • "RimabotulinumtoxinB Injection". MedlinePlus.

grantpiew1971.blogspot.com

Source: https://en.wikipedia.org/wiki/Botulinum_toxin

Enregistrer un commentaire for "what does botulinum toxin do to the body"