Home  ›  How Do You Know if You Have Botulism

How Do You Know if You Have Botulism

Written By Tuesday, 15 March 2022 Add Comment Edit

Neurotoxic poly peptide produced past Clostridium botulinum

Botulinum toxin A
Botulinum toxin 3BTA.png

Ribbon diagram of tertiary construction of BotA (P0DPI1). PDB entry 3BTA.
Clinical data
Trade names Botox, Myobloc, Jeuveau, others
AHFS/Drugs.com Monograph
MedlinePlus a619021
License information
  • United states of america  DailyMed:Jeuveau
Pregnancy
category
  • AU: B3
Routes of
administration		 IM (approved), SC, intradermal, into glands
ATC code
  • M03AX01 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • The states: ℞-only
  • EU: Rx-only
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 concrete data
Formula C 6760 H 10447 North 1743 O 2010 Due south 32
Molar mass 149323.05 grand·mol−1
☒ N check Y  (what is this?) (verify)
Bontoxilysin
Identifiers
EC no. 3.4.24.69
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM contour
PDB structures RCSB PDB PDBe PDBsum
Cistron Ontology AmiGO / QuickGO

Botulinum toxin (BoNT) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.[ane] Information technology 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 also used commercially for medical and cosmetic purposes.

The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and 1000).[three] [four] New types are occasionally found.[five] [6] Types A and B are capable of causing disease in humans, and are likewise used commercially and medically.[7] [viii] [9] Types C–G are less common; types Eastward and F can 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 care for various muscle spasms.

Botulinum toxins are the most stiff toxins known.[eleven] Intoxication can occur naturally as a result of either wound or abdominal infection or by ingesting formed toxin in food. The estimated human lethal dose of type A toxin is one.3–two.1 ng/kg intravenously or intramuscularly, ten–13 ng/kg when inhaled, or thousand ng/kg when taken by mouth.[12] Commercial forms are marketed under the make names Botox (onabotulinumtoxinA), Dysport/Azzalure (abobotulinumtoxinA),[13] Xeomin/Bocouture (incobotulinumtoxinA),[14] and Jeuveau (prabotulinumtoxinA).[xv] [sixteen]

Medical uses [edit]

Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the canonical drug label.[ medical citation needed ]

Muscle spasticity [edit]

Botulinum toxin is used to treat a number of disorders characterized by overactive muscle motion, including cerebral palsy,[7] [8] post-stroke spasticity,[17] post-spinal cord injury spasticity,[18] spasms of the head and cervix,[19] eyelid,[20] vagina,[21] limbs, jaw, and vocal 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 bladder,[25] or clenching of the anus which tin exacerbate anal fissure.[26] Botulinum toxin appears to exist effective for refractory overactive float.[27]

Other musculus disorders [edit]

Strabismus, otherwise known every bit improper centre alignment, is acquired by imbalances in the actions of muscles that rotate the optics. This condition tin can sometimes be relieved by weakening a musculus that pulls as well strongly, or pulls confronting i that has been weakened past disease or trauma. Muscles weakened past toxin injection recover from paralysis after several months, so injection might seem to need to exist repeated, but muscles adjust to the lengths at which they are chronically held,[28] and then that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the adversary shortens, yielding a permanent effect.[29] If binocular vision is good, the brain mechanism of motor fusion, which aligns the eyes on a target visible to both, can stabilize the corrected alignment.[30]

In January 2014, botulinum toxin was canonical past UK's Medicines and Healthcare products Regulatory Bureau for treatment of restricted talocrural joint move due to lower-limb spasticity associated with stroke in adults.[31] [32]

On 29 July 2016, the U.Due south. Food and Drug Administration (FDA) canonical abobotulinumtoxinA for injection for the treatment of lower-limb spasticity in pediatric patients ii years of age and older.[33] [34] AbobotulinumtoxinA is the first and but 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 conditions the drug manufacturer may sell the drug. Withal, prescribers may freely prescribe them for any condition they wish, also known equally off-characterization utilise.[36] Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.[37]

Excessive sweating [edit]

AbobotulinumtoxinA (BTX-A) has been canonical for the handling of excessive underarm sweating of unknown crusade, which cannot exist managed past topical agents.[22] [38]

Migraine [edit]

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

Cosmetic dermatology [edit]

Botulinum toxin being injected in the human confront

In corrective applications, botulinum toxin is considered relatively safe and effective[xl] for reduction of facial wrinkles, especially in the uppermost third of the face.[41] Commercial forms are marketed nether the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, and in the U.S. only, Jeuveau from Evolus, manufactured by Daewoong.[16] The effects of current botulinum toxin injections for glabellar lines ('11'south lines' betwixt the optics) typically last ii to four months and in some cases, product-dependent, with some patients experiencing a longer elapsing of consequence.[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 5 days after injection, with maximum result typically a week following injection.[41] Muscles can be treated repeatedly to maintain the smoothed advent.[41]

Other [edit]

Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,[38] neuropathic pain,[42] and some allergy symptoms.[22] In improver to these uses, botulinum toxin is being evaluated for use in treating chronic hurting.[43] Studies testify that botulinum toxin may exist injected into arthritic shoulder joints to reduce chronic pain and ameliorate range of movement.[44] The use 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 use can occur. Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles.[45]

Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include fractional facial paralysis, musculus weakness, and problem swallowing. Side furnishings are not limited to straight paralysis, however, and can besides include headaches, flu-like symptoms, and allergic reactions.[46] Simply as cosmetic treatments only terminal a number of months, paralysis side effects can have the same durations.[ commendation needed ] At least in some cases, these effects are reported to dissipate in the weeks subsequently treatment.[ citation needed ] Bruising at the site of injection is not a side effect of the toxin, only rather of the manner of administration, and is reported as preventable if the clinician applies force per unit area to the injection site; when it occurs, it is reported in specific cases to terminal 7–11 days.[ citation needed ] When injecting the masseter muscle of the jaw, loss of muscle function can event in a loss or reduction of ability to chew solid foods.[46] With continued loftier doses, the muscles tin can cloudburst or lose strength; enquiry has shown that those muscles rebuild subsequently a break from Botox.[47]

Side effects from therapeutic apply can be much more varied depending on the location of injection and the dose of toxin injected. In general, side effects from therapeutic employ can be more than serious than those that ascend during cosmetic use. These can arise from paralysis of disquisitional musculus groups and tin can include arrhythmia, heart assault, and in some cases, seizures, respiratory arrest, and death.[46] Additionally, side effects mutual in cosmetic apply are also common in therapeutic use, 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 musculus groups, especially when used for treating muscle spasticity in children treated for cerebral palsy.[48] In 2009, the FDA announced that boxed warnings would exist added to bachelor botulinum toxin products, warning of their ability to spread from the injection site.[49] However, the clinical utilize of botulinum toxin A in cognitive palsy children has been proven to be safe with minimal side furnishings.[7] [8] Additionally, the FDA announced name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were given the 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 canonical uses for each.[50] A like alert was issued by Wellness Canada in 2009, warning that botulinum toxin products can spread to other parts of the torso.[51]

Role in affliction [edit]

Botulinum toxin produced by Clostridium botulinum is the cause of botulism.[20] Humans nearly commonly ingest the toxin from eating improperly canned foods in which C. botulinum has grown. Notwithstanding, the toxin can besides be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and tin can cause a status known every bit floppy baby syndrome.[52] In all cases, the toxin can and then spread, blocking nerves and musculus function. In astringent cases, the toxin tin block nerves controlling the respiratory arrangement 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 exam, may help to rule out other causes. If the symptoms of botulism are diagnosed early on, diverse treatments can be administered. In an effort to remove contaminated food that remains in the gut, enemas or induced vomiting may be used.[53] For wound infections, infected material may be removed surgically.[53] Botulinum antitoxin is bachelor and may be used to foreclose the worsening of symptoms, though it volition not opposite existing nerve damage. In astringent cases, mechanical respiration may be used to back up patients suffering from respiratory failure.[53] The nerve damage heals over time, generally over weeks to months.[10] With proper handling, the case fatality charge per unit for botulinum poisoning can be profoundly reduced.[53]

Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (serotypes A, B, East) botulinum antitoxin is derived from equine sources using whole antibodies. The 2d antidote is heptavalent botulinum antitoxin (serotypes A, B, C, D, East, F, G), which is derived from equine antibodies that take been altered to make them less immunogenic. This antidote is effective against all master strains of botulism.[54] [6]

Machinery of action [edit]

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

Botulinum toxin exerts its consequence by cleaving cardinal proteins required for nerve activation. First, the toxin binds specifically to nerves that utilize 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 further into the cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell cytoplasm.[1] BoNTs recognize distinct classes of receptors simultaneously (gangliosides, synaptotagmin and SV2).[57] Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) pregnant that the acetylcholine vesicles cannot demark to the intracellular 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 concatenation, then becomes activated when cleaved by its own proteases.[22] The agile form consists of a ii-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa low-cal concatenation polypeptide.[58] The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, likewise as the domain responsible for mediating translocation of the light concatenation into the jail cell cytoplasm as the vacuole acidifies.[1] [58] The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where information technology 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 jail 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 past the affected cell.[one]

The seven toxin serotypes (A–Yard) are traditionally separated past 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 dissimilar SNARE family unit members.[55] The A, B, and Due east serotypes cause human botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months).[58] Existing toxin types tin recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with the first letter indicating the light chain type and the latter indicating the heavy chain type.[sixty] BoNT/FA received considerable attending under the proper noun "BoNT/H", as it was mistakenly thought information technology could not be neutralized by any existing antitoxin.[six]

Botulinum toxins are closely related to tetanus toxin; the ii are collectively known every bit Clostridium neurotoxins and the low-cal concatenation is classified by MEROPS as family M27. Nonclassical types include BoNT/X (P0DPK1), which is toxic in mice and mayhap in humans;[5] a BoNT/J (A0A242DI27) found in cow Enterococcus;[61] and a BoNT/Wo (A0A069CUU9) found in the rice-colonizing Weissella oryzae.[threescore]

History [edit]

Initial descriptions and discovery of Clostridium botulinum [edit]

I of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in the village of Wildbad in what is now Baden-Württemberg, Deutschland. Thirteen people became sick and vi died afterwards eating pork stomach filled with claret sausage, a local effeminateness. Boosted 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 case reports of "sausage poisoning".[62] Between 1817 and 1822, the German physician Justinus Kerner published the outset complete clarification of the symptoms of botulism, based on all-encompassing clinical observations and animal experiments. He concluded that the toxin develops in bad sausages under anaerobic weather, is a biological substance, acts on the nervous arrangement, and is lethal even in small amounts.[62] Kerner hypothesized that this "sausage toxin" could be used to treat a variety of diseases caused past an overactive nervous system, making him the showtime to suggest that it could be used therapeutically.[63] In 1870, the German language physician Müller coined the term "botulism" to draw the illness caused by sausage poisoning, from the Latin word botulus, pregnant "sausage".[63]

In 1895 Émile van Ermengem, a Belgian microbiologist, discovered what is now chosen Clostridium botulinum and confirmed that a toxin produced past the bacteria causes botulism.[64] On fourteen 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; three of them died. By examining the contaminated ham and performing autopsies on the people who died after eating information technology, van Ermengem isolated an anaerobic microorganism that he called Bacillus botulinus.[62] He also performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from the bacteria. From these he concluded that the bacteria themselves practice not cause foodborne botulism, merely rather produce a toxin that causes the illness subsequently information technology is ingested.[65] As a consequence of Kerner'south and van Ermengem's research, information technology was thought that only contaminated meat or fish could cause botulism. This idea was refuted in 1904 when a botulism outbreak occurred in Darmstadt, Frg because of canned white beans. In 1910, the German microbiologist J. Leuchs published a paper showing that the outbreaks in Ellezelles and Darmstadt were caused by different strains of Bacillus botulinus and that the toxins were serologically singled-out.[62] In 1917, Bacillus botulinus was renamed Clostridium botulinum, as it was decided that term Bacillus should simply refer to a group of aerobic microorganisms, while Clostridium would be but used to describe a group of anaerobic microorganisms.[64] In 1919, Georgina Burke used toxin-antitoxin reactions to identify two strains of Clostridium botulinum, which she designated A and B.[64]

Food canning [edit]

Over the next three decades, 1895–1925, as food canning was approaching a billion-dollar-a-year manufacture, botulism was becoming a public health take a chance. Karl Friedrich Meyer, a Swiss-American veterinary scientist, created a center at the Hooper Foundation in San Francisco, where he adult 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.

Earth War Ii [edit]

With the outbreak of Earth State of war II, 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 starting time clinical product. When the Army's Chemical Corps was disbanded, Schantz moved to the Food Inquiry Plant in Wisconsin, where he manufactured toxin for experimental use and provided information technology 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 enquiry topic. Virtually all toxin treatments are based on this effect 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 bespeak from an activated musculus, to guide injection) of local anesthetics equally a diagnostic technique for evaluating an individual muscle'southward contribution to an eye motion.[68] Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and serpent neurotoxins. Finally, inspired by Daniel B. Drachman's 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.

Afterwards working out techniques for freeze-drying, buffering with albumin, and assuring sterility, say-so, and safety, Scott applied to the FDA for investigational drug utilize, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the commencement strabismus patients in 1977, reported its clinical utility in 1980,[71] and had shortly 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, every bit liability problems were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.[72]

Based on data from thousands of patients collected by 240 investigators, Oculinum Inc (which was before long acquired past Allergan) received FDA approval in 1989 to market place Oculinum for clinical use in the The states to treat adult strabismus and blepharospasm. Allergan and so began using the trademark Botox.[73] This original approval was granted under the 1983 United states Orphan Drug Act.[74]

Cosmetics [edit]

The issue of BTX-A on reducing and eliminating forehead wrinkles was get-go described and published by Richard Clark, Doctor, a plastic surgeon from Sacramento, California. In 1987 Dr. Clark was challenged with eliminating the disfigurement acquired past only the right side of the forehead muscles performance afterward the left side of the forehead was paralyzed during a facelift process. This patient had desired to look ameliorate from her facelift, merely was experiencing bizarre unilateral right forehead countenance elevation while the left countenance drooped, and she constantly demonstrated deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Dr. Clark was enlightened that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the brow announced the same. This report and case report of the Cosmetic apply of Botulinum toxin to treat a Cosmetic complexity of a Cosmetic surgery was the first written report 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 Society of Plastic Surgeons have conspicuously stated "the first described use of the toxin in aesthetic 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 likewise enjoyed diminished facial glabellar lines ("pout lines" betwixt the eyebrows). Alastair Carruthers reported that others at the fourth dimension also noticed these effects and discussed the corrective potential of botulinum toxin.[77] Unlike other investigators, the Carruthers did more just talk about the possibility of using botulinum toxin cosmetically. They conducted a clinical study on otherwise normal individuals whose only concern was their eyebrow furrow. They performed their study during 1987-1989 and presented their results at the 1990 annual meeting of the American Club for Dermatologic Surgery. Their findings were afterwards published in 1992.[78]

Chronic pain [edit]

William J. Binder reported in 2000, that patients who had cosmetic injections around the confront reported relief from chronic headache.[79] This was initially thought to be an indirect issue of reduced muscle tension, simply the toxin is at present known to inhibit release of peripheral nociceptive neurotransmitters, suppressing the key pain processing systems responsible for migraine headache.[80] [81]

Society and civilization [edit]

Economics [edit]

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

The global marketplace for botulinum toxin products, driven by their corrective applications, was forecast to attain $2.ix billion by 2018. The facial aesthetics market place, of which they are a component, was forecast to reach $four.vii billion ($2 billion in the U.S.) in the aforementioned timeframe.[83]

Global Marketplace
In 2019, 6,271,488 Botulinum Toxin procedures were administered worldwide.[84] The Global Botulinum Toxin market size was US$iv.83 billion in 2019 and is projected to reach US$7.71 billion by 2027.[84]
US Market place
In 2020, 4,401,536 Botulinum Toxin Type A procedures were administered.[85] In 2019 the botulinum Toxin market made United states$3.nineteen billion.[84]
Botox cost
Botox toll is by and large determined by the number of units administered (avg. $10.00 - $30.00 per unit of measurement) or by the area ($200–1000) and depends on expertise of a doc, clinic location, number of units, and handling complexity.
Insurance
Botox for medical purposes is usually covered by insurance if deemed medically necessary by your doctor and covers a plethora of medical issues including Overactive Bladder (OAB), urinary incontinence due to neurologic weather, headaches and migraines, TMJ, spasticity in adult patients, cervical dystonia in adult patients, severe axillary hyperhidrosis (or other areas of the body), 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 part of sex activity reassignment surgery. Out-of-pocket botox cost is variable and depends on multiple factors including contraction severity, intervals between injections, doctor'south 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 by insurance.[88]
Hyperhidrosis
Botox for excessive sweating is FDA approved.[45]
Cosmetic
Standard areas for aesthetics botox injections include facial and other areas that can form fine lines and wrinkles due to every mean solar day muscle contractions and/or facial expressions such every bit grinning, frowning, squinting, and raising eyebrows. These areas include the glabellar region betwixt the eyebrows, horizontal lines on the forehead, crow'southward feet around the eyes, and fifty-fifty round bands that grade 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 exist captivated through the eyes, mucous membranes, respiratory tract, and non-intact skin.[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 by and large much more rapid. Evidence suggests that nerve exposure (false by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity.[92] With regard to detection, protocols using NBC detection equipment (such every bit Thou-eight newspaper 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 show in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LDfifty units per milliliter have 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, but the attacks caused no fatalities.[95]

During the early 1980s, German and French newspapers reported that the police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that independent flasks full of Clostridium botulinum, which makes botulinum toxin. Their reports were later on constitute to be incorrect; no such lab was ever institute.[96]

Make names [edit]

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 The states, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and corrective apply. A U.Southward. supplier reported in its visitor materials in 2011 that information technology could "supply the world'south requirements for 25 indications canonical by Government agencies effectually the world" with less than one gram of raw botulinum toxin.[97] Myobloc or Neurobloc, a botulinum toxin type B production, is produced by Solstice Neurosciences, a subsidiary of United states of america 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 corrective uses in the U.Due south. and other countries.[50]

Besides the three primary U.Due south. manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Federal republic of germany by Merz, is too available for both therapeutic and cosmetic utilise in the U.Due south.[98] Lanzhou Institute of Biological Products in China manufactures a BTX-A product; as of 2014, information technology was the merely BTX-A approved in China.[98] BTX-A is also sold equally Lantox and Prosigne on the global market.[99] Neuronox, a BTX-A production, was introduced by Medy-Tox Inc. of S Korea in 2009;[100]

Toxin production [edit]

Botulism toxins are produced by bacteria of the genus Clostridium, namely C. botulinum, C. butyricum, C. baratii and C. argentinense, [101] which are widely distributed, including in soil and dust. Too, the bacteria can be constitute inside 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 environment allows the spores to germinate, after which the bacteria can multiply and produce toxin.[102] Critically, ingestion of toxin rather than spores or vegetative bacteria causes botulism.[102] Botulism is nevertheless known to be transmitted through canned foods not cooked correctly earlier canning or afterwards can opening, so is preventable.[102] Infant botulism arising from consumption of honey or whatever other food that can acquit these spores can be prevented by eliminating these foods from diets of children less than 12 months old.[103]

Organism and toxin susceptibilities [edit]

Proper refrigeration at temperatures beneath 3 °C (38 °F) retards the growth of C. botulinum. The organism is likewise susceptible to high salt, high oxygen, and low pH levels.[10] The toxin itself is apace destroyed past heat, such every bit in thorough cooking.[104] The spores that produce the toxin are estrus-tolerant and volition survive boiling water for an extended period of fourth dimension.[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 beneath), the toxin's activity is also susceptible, post-exposure, to inhibition by protease inhibitors, e.g., zinc-coordinating hydroxamates.[58] [107]

Enquiry [edit]

Blepharospasm and strabismus [edit]

University-based ophthalmologists in the US and Canada further refined the use of botulinum toxin as a therapeutic agent. Past 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of blepharospasm and strabismus.[108] Side effects in handling of this status were deemed to be rare, mild and treatable.[109] The beneficial effects of the injection lasted only 4–six months. Thus, blepharospasm patients required re-injection two or three times a year.[ commendation needed ]

In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug considering of an inability to obtain production liability insurance. Patients became drastic, as supplies of Botox were gradually consumed, forcing him to abandon patients who would accept been due for their next injection. For a period of four months, American blepharospasm patients had to adapt to take their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.[72]

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

Botox has non been approved for whatever pediatric use.[50] It has, however, been used off-label past physicians for several weather, including spastic conditions in pediatric patients with cerebral palsy, a therapeutic form that has resulted in patient deaths.[l] In the case of treatment of infantile esotropia in patients younger than 12 years of age, several studies take yielded differing results.[37] [ better source needed ]

Corrective [edit]

The effect of BTX-A on reducing and eliminating brow 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 acquired by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift process. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow acme while the left eyebrow drooped and she emoted with deep expressive correct forehead wrinkles while the left side was perfectly smooth 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 aforementioned. This study and instance report of the Cosmetic utilise of Botulinum toxin to treat a Cosmetic complication of a Cosmetic surgery was the outset study on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989.[75][76] Editors of the periodical of the American Gild of Plastic Surgeons have clearly stated "the beginning described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."[76]

JD and JA Carruthers also studied and reported in 1992 the use of BTX-A equally a cosmetic treatment.[78] They conducted a report of patients whose only concern was their glabellar forehead wrinkle or furrow. Written report participants were otherwise normal. Sixteen of 17 patients available for follow-upwardly demonstrated a cosmetic improvement. This study was reported at a coming together in 1991. The study for the handling of glabellar frown lines was published in 1992.[78] This outcome was after confirmed by other groups (Brin, and the Columbia University group nether Monte Dandy.[110]). The FDA announced regulatory blessing of botulinum toxin type A (Botox Cosmetic) to temporarily improve the advent of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials.[111] Well before this, the cosmetic apply of botulinum toxin type A became widespread.[112] The results of Botox Cosmetic tin can terminal up to 4 months and may vary with each patient.[113] The U.South. Nutrient and Drug Assistants (FDA) approved an alternative production-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.[114] [115]

BTX-A has also been used in the treatment of glutinous smiles,[116] 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.[117] Botox is usually injected in the three lip elevator 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 pocket-sized (ZMi).[118] [119]

Upper motor neuron syndrome [edit]

BTX-A is at present a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such every bit cerebral palsy,[vii] for muscles with an impaired ability to effectively lengthen. Muscles affected by UMNS frequently are limited past weakness, loss of reciprocal inhibition, decreased movement control, and hypertonicity (including spasticity). In Jan 2014, Botulinum toxin was approved past Great britain'southward Medicines and Healthcare products Regulatory Agency (MHRA) for the handling of ankle disability due to lower limb spasticity associated with stroke in adults.[31] Joint motion may be restricted by severe musculus 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 can let improved reciprocal motion, so improved power to move and exercise.[7]

Sialorrhea [edit]

Sialorrhea is a status where oral secretions are unable to be eliminated, causing pooling of saliva in the mouth. This condition tin can be caused past diverse neurological syndromes such equally Bell'due south palsy, mental retardation, and cerebral palsy. Injection of BTX-A into salivary glands is useful in reducing the secretions.[120]

Cervical dystonia [edit]

BTX-A is usually used to treat cervical dystonia, only it can go ineffective afterwards a time. Botulinum toxin blazon B (BTX-B) received FDA approval for treatment of cervical dystonia on 21 Dec 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 name Botox) received FDA approval for handling of chronic migraines on 15 October 2010. The toxin is injected into the head and neck to treat these chronic headaches. Approving followed evidence presented to the agency from ii studies funded by Allergan showing a very slight improvement in incidence of chronic migraines for migraine sufferers undergoing the Botox handling.[121] [122]

Since then, several randomized control trials accept shown botulinum toxin blazon A to improve headache symptoms and quality of life when used prophylactically for patients with chronic migraine[123] who exhibit headache characteristics consistent with: pressure perceived from exterior source, shorter total elapsing of chronic migraines (<xxx years), "detoxification" of patients with coexisting chronic daily headache due to medication overuse, and no current history of other preventive headache medications.[124]

Low [edit]

A few small-scale trials accept institute benefits in people with low.[125] [126] Research is based on the facial feedback hypothesis.[127]

Premature ejaculation [edit]

The drug for the treatment of premature ejaculation has been under development since Baronial vii, 2013, and is in Stage II of the FDA trials.[126] [128]

References [edit]

  1. ^ 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): 274–279. 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 direction of cervical dystonia". Drugs. 62 (4): 705–722. doi:10.2165/00003495-200262040-00011. PMID 11893235. S2CID 46981635.
  3. ^ Janes LE, Connor LM, Moradi A, Alghoul M (April 2021). "Current Employ of Corrective Toxins to Improve Facial Aesthetics". Plastic and Reconstructive Surgery. 147 (four): 644e–657e. doi:x.1097/PRS.0000000000007762. PMID 33776040. S2CID 232408799.
  4. ^ Rosales RL, Bigalke H, Dressler D (February 2006). "Pharmacology of botulinum toxin: differences between type A preparations". European Journal of Neurology. 13 (Suppl 1): 2–x. doi:x.1111/j.1468-1331.2006.01438.10. PMID 16417591. S2CID 32387953.
  5. ^ a b "Botulism toxin X: Time to update the textbooks, thanks to genomic sequencing". Boston Children'south Hospital. 7 Baronial 2017. Retrieved 28 October 2019.
  6. ^ a b c "Study: Novel botulinum toxin less dangerous than thought". CIDRAP. University 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. 8 (3): e0119. doi:ten.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 (x): CD001408. doi:10.1002/14651858.CD001408.pub2. PMC6779591. PMID 31591703.
  9. ^ American Society of Health-System Pharmacists (27 October 2011). "OnabotulinumtoxinA (Botulinum Toxin Type A) Monograph for Professionals". drugs.com . Retrieved iv March 2015.
  10. ^ a b c "Botulism: Cardinal facts". Earth Health System.
  11. ^ Košenina South, Masuyer 1000, Zhang S, Dong M, Stenmark P (June 2019). "Crystal structure of the catalytic domain of the Weissella oryzae botulinum-similar toxin". FEBS Letters. 593 (12): 1403–1410. doi:10.1002/1873-3468.13446. PMID 31111466.
  12. ^ Arnon SS, Schechter R, Inglesby Telly, Henderson DA, Bartlett JG, Ascher MS, et al. (Feb 2001). "Botulinum toxin every bit a biological weapon: medical and public health management". JAMA. 285 (8): 1059–1070. doi:10.1001/jama.285.eight.1059. PMID 11209178.
  13. ^ "Drug Approval Parcel: Dysport (abobotulinumtoxin) NDA #125274s000". U.S. Nutrient and Drug Assistants (FDA). 17 Baronial 2011. Retrieved 23 Nov 2019.
  14. ^ "Drug Approval Package: Brand Name (Generic Name) NDA #". accessdata.fda.gov. 24 Dec 1999. Retrieved 23 Nov 2019.
  15. ^ "Drug Approval Package: Jeuveau". U.S. Food and Drug Administration (FDA). 5 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 Most Affordable Contraction Injectable". refinery29.com.
  17. ^ Ozcakir S, Sivrioglu Yard (June 2007). "Botulinum toxin in poststroke spasticity". Clinical Medicine & Research. 5 (two): 132–138. doi:x.3121/cmr.2007.716. PMC1905930. PMID 17607049.
  18. ^ Yan X, Lan J, Liu Y, Miao J (November 2018). "Efficacy and Safety of Botulinum Toxin Blazon A in Spasticity Caused by Spinal String Injury: A Randomized, Controlled Trial". Medical Science Monitor. 24: 8160–8171. doi:10.12659/MSM.911296. PMC6243868. PMID 30423587.
  19. ^ "Cervical dystonia - Symptoms and causes". Mayo Clinic. 28 January 2014. Retrieved 14 Oct 2015.
  20. ^ a b Shukla HD, Sharma SK (2005). "Clostridium botulinum: a bug with beauty and weapon". Disquisitional Reviews in Microbiology. 31 (1): 11–18. doi:10.1080/10408410590912952. PMID 15839401. S2CID 2855356.
  21. ^ Pacik PT (Dec 2009). "Botox treatment for vaginismus". Plastic and Reconstructive Surgery. 124 (6): 455e–456e. doi:10.1097/PRS.0b013e3181bf7f11. PMID 19952618.
  22. ^ a b c d Felber ES (October 2006). "Botulinum toxin in primary intendance 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 S, Grendell JH (March 2013). "Endoscopic approaches to treatment of achalasia". Therapeutic Advances in Gastroenterology. 6 (two): 115–135. doi:10.1177/1756283X12468039. PMC3589133. PMID 23503707.
  24. ^ Long H, Liao Z, Wang Y, Liao L, Lai W (Feb 2012). "Efficacy of botulinum toxins on bruxism: an testify-based review". International Dental Journal. 62 (ane): 1–5. doi:10.1111/j.1875-595X.2011.00085.x. PMID 22251031.
  25. ^ Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, et al. (October 2011). "Gimmicky management of lower urinary tract affliction 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 Southward, Abbas MA (2007). "Anal crack: a mutual cause of anal hurting". The Permanente Journal. xi (4): 62–65. doi:10.7812/tpp/07-072. PMC3048443. PMID 21412485.
  27. ^ Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D (December 2011). Duthie JB (ed.). "Botulinum toxin injections for adults with overactive bladder syndrome". The Cochrane Database of Systematic Reviews (12): CD005493. doi:ten.1002/14651858.CD005493.pub3. PMID 22161392.
  28. ^ Scott AB (1994). "Change of eye muscle sarcomeres according to heart position". Journal of Pediatric Ophthalmology and Strabismus. 31 (2): 85–88. doi:x.3928/0191-3913-19940301-05. PMID 8014792.
  29. ^ Simpson L (2 December 2012). Botulinum Neurotoxin and Tetanus Toxin. Elsevier. ISBN978-0-323-14160-4.
  30. ^ "Could my child's crossed center exist 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 Use Archived 22 Feb 2014 at the Wayback Machine. dddmag.com. 4 February 2014
  32. ^ "UK's MHRA approves Botox for treatment of ankle disability in stroke survivors". world wide web.thepharmaletter.com . Retrieved 16 March 2020.
  33. ^ "FDA Approved Drug Products – Dysport". U.South. Food and Drug Assistants (FDA). Archived from the original on 8 November 2016. Retrieved 7 November 2016. Public Domain This commodity incorporates text from this source, which is in the public domain .
  34. ^ Pavone V, Testa G, Restivo DA, Cannavò L, Condorelli G, Portinaro NM, Sessa G (xix February 2016). "Botulinum Toxin Treatment for Limb Spasticity in Childhood Cerebral Palsy". Frontiers in Pharmacology. seven: 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 (four): 367–373. doi:10.1007/s40272-017-0242-four. PMID 28623614. S2CID 24857218.
  36. ^ Wittich CM, Burkle CM, Lanier WL (October 2012). "Ten mutual questions (and their answers) about off-label drug employ". Mayo Clinic Proceedings. 87 (10): 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 Treatment & Management". Medscape. Retrieved vi 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 (v): 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 Small R (August 2014). "Botulinum toxin injection for facial wrinkles". American Family Physician. 90 (three): 168–175. PMID 25077722.
  42. ^ Mittal So, Safarpour D, Jabbari B (February 2016). "Botulinum Toxin Handling of Neuropathic Pain". Seminars in Neurology. 36 (1): 73–83. doi:10.1055/s-0036-1571953. PMID 26866499.
  43. ^ Charles PD (November 2004). "Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses". American Journal of Wellness-System Chemist's shop. 61 (22 Suppl 6): S11–S23. doi:10.1093/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:ten.1002/14651858.cd008271.pub2. PMID 20824874.
  45. ^ a b Nigam PK, Nigam A (2010). "Botulinum toxin". Indian Journal of Dermatology. 55 (1): eight–14. doi:x.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 type A injections: adverse events reported to the Us Nutrient and Drug Administration in therapeutic and corrective cases". Journal of the American Academy of Dermatology. 53 (3): 407–415. doi:x.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 Use". U.S. Food and Drug Assistants (FDA). 8 February 2008. Archived from the original on 2 March 2012. Retrieved half dozen 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 Inverse". Pharmaceutical Online. iv August 2009. Retrieved 16 July 2019.
  50. ^ a b c d "Information for Healthcare Professionals: OnabotulinumtoxinA (marketed every bit Botox/Botox Corrective), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed every bit Myobloc)". U.S. Food and Drug Administration (FDA). 13 September 2015. Archived from the original on xiii September 2015. Retrieved 1 September 2015. Public Domain This commodity incorporates text from this source, which is in the public domain .
  51. ^ "Botox chemical may spread, Health Canada confirms". CBC News. 13 Jan 2009. Archived from the original on 21 February 2009.
  52. ^ "Kinds of Botulism". Centers for Disease 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 (Jan 2014). "A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins". The Periodical 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 (ten): 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 action". Arquivos de Neuro-Psiquiatria. 63 (1): 180–185. doi:10.1159/000083259. PMID 15830090. S2CID 16307223.
  57. ^ Dong, Min; Masuyer, Geoffrey; Stenmark, Pål (20 June 2019). "Botulinum and Tetanus Neurotoxins". Annual Review of Biochemistry. 88 (ane): 811–837. doi:10.1146/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 (December 2010). "Small molecule inhibitors every bit countermeasures for botulinum neurotoxin intoxication". Molecules. sixteen (ane): 202–220. doi:10.3390/molecules16010202. PMC6259422. PMID 21193845.
  59. ^ Hill KK, Smith TJ (2013). Rummel A, Binz T (eds.). "Genetic diverseness within Clostridium botulinum serotypes, botulinum neurotoxin factor clusters and toxin subtypes". Current Topics in Microbiology and Immunology. Springer. 364: 1–20. doi:10.1007/978-3-642-33570-9_1. ISBN978-3-642-33569-3. 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. 10 (10): 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 (three): 310–317. doi:x.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 thought of the therapeutic use of the toxin". Movement Disorders. 19 (Supplement viii): S2–S6. doi:10.1002/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:ten.1093/asj/sjw284. PMC5434488. PMID 28388718.
  65. ^ Pellett S (June 2012). "Learning from the by: historical aspects of bacterial toxins equally pharmaceuticals". Current Opinion in Microbiology. 15 (3): 292–299. doi:ten.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:x.1126/science.103.2681.613. PMID 21026141.
  67. ^ Burgen AS, Dickens F, Zatman LJ (Baronial 1949). "The action of botulinum toxin on the neuro-muscular junction". The Journal of Physiology. 109 (one–two): 10–24. doi:x.1113/jphysiol.1949.sp004364. PMC1392572. PMID 15394302.
  68. ^ Magoon E, Cruciger Yard, Scott AB, Jampolsky A (May 1982). "Diagnostic injection of Xylocaine into extraocular muscles". Ophthalmology. 89 (5): 489–491. doi:10.1016/s0161-6420(82)34764-8. 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:x.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 equally an culling to strabismus surgery". Ophthalmology. 87 (10): 1044–1049. doi:10.1016/s0161-6420(80)35127-0. PMID 7243198.
  72. ^ a b Boffey PM (xiv 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 Health and Human being Services (xxx April 2009). "Re: Docket No. FDA-2008-P-0061" (PDF). U.S. Food and Drug Assistants (FDA). Archived from the original (PDF) on 6 July 2010. Retrieved 26 July 2010. Public Domain This commodity incorporates text from this source, which is in the public domain .
  74. ^ Wellman-Labadie O, Zhou Y (May 2010). "The United states Orphan Drug Act: rare disease research stimulator or commercial opportunity?". Health Policy. 95 (2–3): 216–228. doi:x.1016/j.healthpol.2009.12.001. PMID 20036435.
  75. ^ a b Clark RP, Berris CE (August 1989). "Botulinum toxin: a treatment for facial asymmetry caused by facial nervus paralysis". Plastic and Reconstructive Surgery. 84 (two): 353–355. doi:10.1097/01.prs.0000205566.47797.8d. PMID 2748749.
  76. ^ a b Rohrich, Rod J.; Janis, Jeffrey E.; Fagien, Steven; Stuzin, James M. (October 2003). "The Cosmetic Utilize 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 use of botulinum toxin A and B". Clinics in Dermatology. 21 (6): 469–472. doi:ten.1016/j.clindermatol.2003.11.003. PMID 14759577.
  78. ^ a b Carruthers JD, Carruthers JA (Jan 1992). "Treatment of glabellar frown lines with C. botulinum-A exotoxin". The Journal of Dermatologic Surgery and Oncology. xviii (one): 17–21. doi:10.1111/j.1524-4725.1992.tb03295.x. PMID 1740562.
  79. ^ Folder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM (December 2000). "Botulinum toxin blazon A (BOTOX) for treatment of migraine headaches: an open-label written report". Otolaryngology–Head and Cervix Surgery. 123 (half dozen): 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 treatment of migraine and tension headaches in adults: a meta-analysis". JAMA. 307 (xvi): 1736–1745. doi:10.1001/jama.2012.505. PMID 22535858.
  81. ^ Ramachandran R, Yaksh TL (September 2014). "Therapeutic utilise of botulinum toxin in migraine: mechanisms of activeness". British Periodical of Pharmacology. 171 (18): 4177–4192. doi:x.1111/bph.12763. PMC4241086. PMID 24819339.
  82. ^ "New plastic surgery statistics reveal trends toward trunk enhancement". Plastic Surgery. 11 March 2019. Archived from the original on 12 March 2019.
  83. ^ Chapman Fifty (10 May 2012). "The global botox market forecast to reach $2.9 billion by 2018". Archived from the original on vi August 2012. Retrieved v October 2012.
  84. ^ a b c "Botulinum Toxin Market". Fortune Business Insights.
  85. ^ "2020 National Plastic Surgery Statistics: Corrective 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 utilize" (PDF). Highlights of Prescribing Information. United states of america Food and Drug Administration.
  88. ^ "Botox for Migraine". The American Migraine Foundation.
  89. ^ "BOTOX® Procedures: What is BOTOX® & How Does information technology Work". The American Academy of Facial Esthetics.
  90. ^ Koirala J, Basnet S (xiv July 2004). "Botulism, Botulinum Toxin, and Bioterrorism: Review and Update". Medscape. Cliggott Publishing. Archived from the original on 1 June 2011. Retrieved 14 July 2010.
  91. ^ Public Health Agency of Canada (xix 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 sixteen September 2020. M8 paper is a chemically-treated, dye-impregnated paper used to detect liquid substances for the presence of V- and K-type nervus agents and H- and Fifty-type blister agents.
  94. ^ Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Ca.: Biomedical Publications. pp. 260–61. ISBN978-0-9626523-9-4.
  95. ^ Arnon SS, Schechter R, Inglesby Television set, Henderson DA, Bartlett JG, Ascher MS, et al. (Working Group on Civilian Biodefense) (February 2001). "Botulinum toxin equally a biological weapon: medical and public health management". JAMA. 285 (8): 1059–1070. doi:ten.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. Wiley-Liss. doi:10.1002/0471686786.ebd0012.pub2. ISBN978-0-471-68678-one.
  97. ^ "2011 Allergan Almanac Study" (PDF). Allergan. Retrieved 3 May 2012. Run into PDF p. seven.
  98. ^ a b c Walker TJ, Dayan SH (Feb 2014). "Comparison and overview of currently available neurotoxins". The Periodical of Clinical and Aesthetic Dermatology. 7 (2): 31–39. PMC3935649. PMID 24587850.
  99. ^ "Botulinum Toxin Type A". Hugh Source (International) Limited. Retrieved fourteen July 2010.
  100. ^ Petrou I (Bound 2009). "Medy-Tox Introduces Neuronox to the Botulinum Toxin Arena" (PDF). The European Aesthetic Guide. Archived from the original (PDF) on 20 March 2013. Retrieved 9 December 2009.
  101. ^ Schantz EJ, Johnson EA (March 1992). "Properties and apply of botulinum toxin and other microbial neurotoxins in medicine". Microbiological Reviews. 56 (1): eighty–99. doi:10.1128/MMBR.56.1.80-99.1992. PMC372855. PMID 1579114.
  102. ^ a b c d "About Botulism | Botulism | CDC". world wide web.cdc.gov. nine October 2018. Retrieved thirteen May 2020.
  103. ^ "Botulism". Centers for Disease Control and Prevention (CDC). 19 August 2019. Retrieved 28 Baronial 2019.
  104. ^ Licciardello JJ, Nickerson JT, Ribich CA, Goldblith SA (March 1967). "Thermal inactivation of type Due east botulinum toxin". Applied Microbiology. 15 (2): 249–256. doi:x.1128/AEM.fifteen.2.249-256.1967. PMC546888. PMID 5339838.
  105. ^ Setlow P (April 2007). "I volition survive: DNA protection in bacterial spores". Trends in Microbiology. 15 (4): 172–180. doi:10.1016/j.tim.2007.02.004. PMID 17336071.
  106. ^ "Fact sheets - Botulism". World Health Organisation. ten January 2018. Retrieved 23 March 2019.
  107. ^ Capková K, Salzameda NT, Janda KD (October 2009). "Investigations into small molecule non-peptidic inhibitors of the botulinum neurotoxins". Toxicon. 54 (5): 575–582. doi:x.1016/j.toxicon.2009.03.016. PMC2730986. PMID 19327377.
  108. ^ Flemish region M, Tischler A, Wise J, Williams F, Beneish R, Auger 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 center 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 Chiliad, Blitzer A (April 1994). "Botulinum toxin A: a novel method to remove periorbital wrinkles". Facial Plastic Surgery. ten (ii): 141–146. doi:10.1055/southward-2008-1064563. PMID 7995530.
  111. ^ "Botulinum Toxin Blazon A Production Approval Information – Licensing Activeness 4/12/02". U.Due south. Food and Drug Administration (FDA). 29 Oct 2009. Archived from the original on 8 March 2010. Retrieved 26 July 2010. Public Domain This article incorporates text from this source, which is in the public domain .
  112. ^ Giesler One thousand (2012). "How Doppelgänger Brand Images Influence the Market place Creation Process: Longitudinal Insights from the Ascension of Botox Cosmetic". Journal of Marketing. 76 (half-dozen): 55–68. doi:10.1509/jm.10.0406. S2CID 167319134.
  113. ^ "Botox Corrective (onabotulinumtoxinA) Product Information". Allergan. 22 January 2014.
  114. ^ "Allergan Receives FDA Blessing for Starting time-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.S., 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 (Dec 2014). "BOTOX: Broadening the Horizon of Dentistry". Periodical 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. (January 2009). "Surface anatomy of the lip lift muscles for the treatment of gummy grin using botulinum toxin". The Bending Orthodontist. 79 (1): 70–77. doi:10.2319/091407-437.1. PMID 19123705.
  118. ^ Gracco A, Tracey S (May 2010). "Botox and the gummy grinning". Progress in Orthodontics. xi (ane): 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 approach based on the gingival exposure area". Journal of the American Academy of Dermatology. 63 (6): 1042–1051. doi:ten.1016/j.jaad.2010.02.053. PMID 21093661.
  120. ^ Khan WU, Campisi P, Nadarajah S, Shakur YA, Khan N, Semenuk D, et al. (April 2011). "Botulinum toxin A for treatment of sialorrhea in children: an constructive, minimally invasive approach". Archives of Otolaryngology–Head & Cervix Surgery. 137 (4): 339–344. doi:10.1001/archoto.2010.240. PMID 21242533.
  121. ^ "FDA approves Botox to care for chronic migraine". U.Due south. Food and Drug Administration (FDA) (Press release). 19 October 2010. Archived from the original on nineteen October 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 programme". Headache. l (6): 921–936. doi:10.1111/j.1526-4610.2010.01678.10. 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-v. PMID 20425239. S2CID 32191932.
  125. ^ Magid 1000, 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 E, Rosenthal NE (May 2014). "Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial". Periodical of Psychiatric Research. 52: 1–6. doi:10.1016/j.jpsychires.2013.eleven.006. PMID 24345483.
  128. ^ Allergan (21 September 2018). "An Exploratory Report of the Safety and Efficacy of Botox for the Treatment of Premature Ejaculation".

External links [edit]

  • A Toxicant That Can Heal from the U.S. Food and Drug Assistants (FDA)
  • BotDB: extensive resources on BoNT structures, inhibitors, kinetics, and literature
  • A consumer sociological investigation of Botox Corrective'south Rise
  • Overview of all the structural data bachelor in the PDB for UniProt: P0DPI1 (Botulinum neurotoxin type A) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: P10844 (Botulinum neurotoxin blazon B) at the PDBe-KB.
  • Overview of all the structural data 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 Information Portal. U.Due south. National Library of Medicine.
  • "AbobotulinumtoxinA". Drug Information Portal. U.S. National Library of Medicine.
  • "Botox prescribing data". DailyMed.
  • "Myobloc- rimabotulinumtoxinb injection, solution characterization prescribing information". DailyMed.
  • "Dysport prescribing information". DailyMed.
  • "AbobotulinumtoxinA Injection". MedlinePlus.
  • "IncobotulinumtoxinA Injection". MedlinePlus.
  • "OnabotulinumtoxinA Injection". MedlinePlus.
  • "PrabotulinumtoxinA-xvfs Injection". MedlinePlus.
  • "RimabotulinumtoxinB Injection". MedlinePlus.

johnsonsuccionoth.blogspot.com

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

0 Response to "How Do You Know if You Have Botulism"

Post a Comment

Subscribe to: Post Comments (Atom)

Iklan Atas Artikel

Iklan Tengah Artikel 1

Iklan Tengah Artikel 2

Iklan Bawah Artikel