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Historical aspects of botulinum toxin Justinus Kerner (1786–1862) and the “sausage poison”

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  • Klinikum Nürnberg - Paracelsus Medical University
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... After clinical follow-up of his patients, he correctly concluded that the substance 'sausage poison' or 'fatty acid' paralyzed the skeletal muscle function and the parasympathetic nervous system and proposed its use as a therapeutic agent in neurological diseases characterized by involuntary movements. [7][8][9] In 1870, the name sausage poison was replaced by botulinum toxin (from the Latin word botulus, meaning 'sausage'). 7 Kerner is remembered as the intellectual founder of modern BoNT therapy; however, BoNT was only first purified in 1945, and its therapeutic use was initiated in the 1980s by Alan B Scott in patients with strabismus. ...
... [7][8][9] In 1870, the name sausage poison was replaced by botulinum toxin (from the Latin word botulus, meaning 'sausage'). 7 Kerner is remembered as the intellectual founder of modern BoNT therapy; however, BoNT was only first purified in 1945, and its therapeutic use was initiated in the 1980s by Alan B Scott in patients with strabismus. [7][8][9][10][11] BoNT is a complex mixture of proteins that include a botulinum neurotoxin and several nontoxic proteins, produced by Clostridium botulinum. ...
... 7 Kerner is remembered as the intellectual founder of modern BoNT therapy; however, BoNT was only first purified in 1945, and its therapeutic use was initiated in the 1980s by Alan B Scott in patients with strabismus. [7][8][9][10][11] BoNT is a complex mixture of proteins that include a botulinum neurotoxin and several nontoxic proteins, produced by Clostridium botulinum. 9,11 The functional portion of the neurotoxin is a peptide composed of a 100-kDa heavy chain and a 50-kDa light chain, which blocks the release of acetylcholine at the nerve terminals, causing the denervation of the motor terminals. ...
Article
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The term “movement disorders” encompass all disorders hypokinetic and hyperkinetic, which were previously known as extra-pyramidal syndromes. With the definition of movement disorders and their diagnostic criteria and classifications, new studies for therapeutics could be performed. New drugs were launched, functional neurosurgery was developed, and the introduction of botulinum toxin (BoNT) for hyperkinesias was introduced. BoNT is an important therapy for dystonia, tics, myoclonus and tremors. The aim of this review is to present the new and well-established uses of BoNT for movement disorders.
... 13 The Wildbad outbreak was later traced to a dish of cooked pork stomach filled with blood sausage. 14 During the 19th century, doctors recognized that the Wildbad outbreak was not an isolated incident. Indeed, poor hygiene associated with the economic depression in the wake of the Napoleonic War (1795-1813) probably contributed to numerous outbreaks of fatal food poisoning, including several cases of botulism from smoked blood sausages. ...
... Indeed, poor hygiene associated with the economic depression in the wake of the Napoleonic War (1795-1813) probably contributed to numerous outbreaks of fatal food poisoning, including several cases of botulism from smoked blood sausages. 14,15 In July 1802, for example, the government in Stuttgart warned the public about eating smoked blood sausages. 14 Justinus Andreas Christian Kerner, a German physician, poet, and medical writer, published the first case studies on botulinum toxicity in 1817 and 1820. ...
... 14,15 In July 1802, for example, the government in Stuttgart warned the public about eating smoked blood sausages. 14 Justinus Andreas Christian Kerner, a German physician, poet, and medical writer, published the first case studies on botulinum toxicity in 1817 and 1820. 14- 16 Kerner was interested in these cases of food poisoning and death through his work as a medical officer in Wildbad in 1811. ...
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During the late 1960s and early 1970s, Alan Scott showed that intramuscular injections of botulinum toxin (BoNT) corrected nonaccommodative strabismus without resorting to surgery. The UK doctors who trained with Scott soon realized the significant potential offered by BoNT type A as a therapeutic option for several difficult-to-treat diseases. This led to a collaboration between these pioneering clinicians and the Centre for Applied Microbiology and Research at Porton Down, United Kingdom, and, in turn, to the development and commercialization of abobotulinumtoxinA as Dysport (Dystonia/Porton Down; Ipsen Biopharm Ltd., Wrexham, UK). Dysport was approved in Europe for the treatment of specific dystonias in December 1990 and now has marketing authorizations in 75 countries. Since then, the use of BoNT in therapeutic and aesthetic indications has grown year-on-year, and continues to expand well beyond Scott’s initial aim. For example, ongoing trials are assessing potential new indications for BoNT-A, including acne and psoriasis. Furthermore, a growing number of other BoNT products, often termed “biosimilars,” together with innovative formulations of well-established BoNT types, are likely to reach the market over the next few years. This review focuses on the history of Dysport to mark the 25th anniversary of its first launch in the United Kingdom.
... They stemmed from prussic acid which is in the sausage for those cases. [4,5] Between 1817 and 1822 local medical officer Justinus Kerner analyzed some 230 cases [1] and characterized them, which we know botulism here and now. But at that moment he termed it as ''sausage poison'' or ''fatty poison''. ...
... Experiments showed the motor system is affected by the toxin. [4] Overall, Kerner assumed that low-dose toxins could be used to control hyperextension and hyperflexion as a therapy. German physician Müller (1870) uses the term 'botulism (from the Latin word botulus, meaning ''sausage'')' to refer to sausage poison. ...
Article
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Food poisoning, in general, is unfortunate, but one type, in particular, is regarded the most dangerous: botulism. The name comes from the Latin bachelors, which means "sausage." It was first identified in processed meat. Foodborne botulism is caused by clostridial organisms that proliferate in the guts of infected people, then produce toxins that are absorbed and have systemic consequences.
... The German physician, Justinus Kerner (1786-1862) was the first who developed the idea of a possible therapeutic use of botulinum toxin. 1 In 1973, for the first time, Scott in Smith Kettewell Eye Research Center used Botulinum toxin (BTX) in human to treat strabismus. In 1989, US-FDA approved BTX for the treatment of strabismus, belpharospasm and hemifacial spasm in patients younger than 12 years old. ...
... In 2001, the United Kingdom approved Botox for axillary hyperhidrosis and Canada approach Botox for axillary hyperhidrosis, focal muscle spasticity, and cosmetic treatment of wrinkles at the brow line. 1 ...
Article
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Botulinum toxin (BTX) is also well-known as Botox is produced by a gram-positive anaerobic bacterium called Clostridium botulinum. Generally, clinical manifestations of BTX can be observed after consumption of contaminated food, from colonization of the infant gastrointestinal tract, as well as following the infection of the wound to this bacterium. There are seven types of this neurotoxin labeled as A, B, C (C1, C2), D, E, and F. Human botulinum is caused by types A, B, E and rarely F. The most common clinical symptoms of BTX in cosmetic goals are cervical dystonia, severe primary axillary hyperhidrosis, strabismus, neurogenic detrusor over-activity, chronic migraine, upper limb spasticity and blepharospasm. Botox has a wide range of therapeutic uses and occasionally patients receiving this treatment may experience botulism symptom including local and even distant and autonomic symptoms. Despite the efficacies of Botox in treatment of myriad neurologic and cosmetic conditions, it may carry some risk of sever adverse effects which may be the result of local or systemic spreading of the drug. Our patient was a 22 years old man who received Botox for axillary hyperhidrosis after two weeks, when most of generalized complications of botulinum toxin appeared. This case was introduced for being aware of dangerous complication of Botox. Pyridostigmine could relieve symptoms of the patient.
... Botulinum toxin type A (BTA) is a protein synthesized by an anaerobic bacteria, Clostridium botulinum, and is one of the strongest toxins found in nature (1,2). It is a cause of poisoning (botulism), but it also has a beneficial effect on reducing muscle spasm and has found widespread use in medicine, with indications increasing year by year. ...
... In 1978, he applied BTA for the first time in humans, in the treatment of strabismus. The tests have proven to be successful, marking the beginning of a series of studies that have examined the effects of BTA in many conditions of muscular hyperactivity over the next decade (1,2,8). The U.S. National Institutes of Health, 1990. ...
... Its potential for therapeutic use was first noticed in 1817 by physician Justinus Kerner, who coined the term botulism. 1 In 1897, bacteriologist Emile van Ermengem isolated the causative bacterium C. botulinum. 2 It was later discovered that the toxin induces muscle paralysis by inhibiting acetylcholine release from presynaptic motor neurons at the neuromuscular junction 3 and was then mainly investigated as a treatment for medical conditions involving excessive or abnormal muscular contraction. ...
... What is the advantage for them to produce a lethal toxin that can kill a host at a distance from the bacterial replication site? Since the identification of botulism as a natural poison-caused disease by Justinus Kerner [122,123], two centuries of hard work have been necessary to understand botulism's mechanisms at the molecular level. The natural history of the BoNTs and their producing bacteria is still in progress. ...
Article
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Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and chemical poisonous compounds. Although a great effort has been made to understand their mode of action, some questions are still open. Why, and for what benefit, have environmental bacteria that accidentally interact with their host engineered so diverse and so specific toxins targeting one of the most specialized physiological processes, the neuroexocytosis of higher organisms? The extreme potency of BoNT does not result from only one hyperactive step, but in contrast to other potent lethal toxins, from multi-step activity. The cumulative effects of the different steps, each having a limited effect, make BoNTs the most potent lethal toxins. This is a unique mode of evolution of a toxic compound, the high potency of which results from multiple steps driven by unknown selection pressure, targeting one of the most critical physiological process of higher organisms.
... 1980'de ilk kez insanda strabismus tedavisinde denenen ve 1989'da FDA (Food and Drug Administration) onayı alınan BT'nin kullanım alanı hızla genişlemiştir (34). İnmeli hastalarda spastisite tedavisinde BT ilk kez 1989 yılında Das ve Park tarafından yapılan çalışmada kullanılmıştır (35). ...
Chapter
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ÖZET: İnme sonrası yüksek oranda görülen üst ekstremite spastisitesi, aktif fonksiyonu etkileyerek hastaların günlük yaşamdaki bağımsızlığını etkileyen en önemli bozukluklardandır. Üst ekstremite spastisitesinin yönetiminde fizyoterapi uygulamaları, farmakolojik ve cerrahi uygulamalar kullanılmaktadır. Botulinum toksin, sahip olduğu avantajlar ile birlikte spastisite yönetiminde en yaygın kullanılan farmakolojik yöntemlerdendir. Literatürde, presinaptik terminallerde asetilkolinin salınımı engelleyerek sinir iletimini önleyen botulinum toksinin üst ekstremite spastisitesinde uygulanmasının spastisiteyi azaltarak fonksiyon gelişimini sağladığı bilinmektedir. Ancak var olan çalışmalarda botulinum toksin enjeksiyonuyla kombine uygulanan çeşitli fiziksel ajanların ve rehabilitasyon uygulamalarının üst ekstremite spastisitesinin yönetiminde sadece botulinum toksin uygulamasına göre daha etkili olduğu vurgulanmaktadır. Bu bölümde inme sonrası üst ekstremite spastisitesinde botulinum toksin ile birlikte uygulanan fizyoterapi ve rehabilitasyon uygulamaları incelenecektir. ABSTRACT: Upper extremity spasticity, which is highly seen after stroke, is one of the most important disorders affecting the active function and the independence in activities of daily living. Physiotherapy, pharmacological and surgical treatments are used in the management of upper extremity spasticity. Botulinum toxin, which prevents nerve conduction by inhibiting the release of acetylcholine in presynaptic terminals, is known to be effective in upper extremity spasticity by decreasing spasticity and improving function. However , it is emphasized that various physical modalities and rehabilitation applications combined with botulinum toxin are more effective in management of upper extremity spasticity than botulinum toxin injection alone. In this section, the physiotherapy and rehabilitation applications combined with botulinum toxin injection in upper extremity spasticity after stroke will be examined.
... In 1870, John Muller coined the term "botulism" (the Latin root botulus means "sausage") and in 1895, van Ermengem isolated the bacterium for the first time. 2,3 The discovery of the bacterium and toxin led to the investigation of its use as a treatment for strabismus. 3,4 Finally, in 1989, it was FDA approved as a therapy for strabismus, blepharospasm, and hemifacial spasm. ...
Article
Full-text available
Botulinum toxin (BoNT) is a potent biological exotoxin produced from Clostridium botulinum. Although it was first used therapeutically to treat strabismus, its clinical role has since expanded rapidly over the years to include treatment of a variety of head and neck, gastrointestinal, urogenital, musculoskeletal, neurological, dermatological, and cosmetic disorders. The main purpose of this review is to provide a brief updated overview of the history, mechanism of action, and clinical applications of BoNT therapy across multiple medical specialties, including the most common adverse effects and recommended Botox dosages. Methods: A literature review was conducted in the PubMed database limited to English language articles. Specific search terms related to botulinum toxin in combination with various subspecialty fields were used, and relevant articles were identified and analyzed. The reference section for each article was also searched to find additional articles. Results: BoNT is a powerful therapeutic tool and has a vast array of clinical uses in many specialties, including ophthalmology, neurology, plastic surgery, dermatology, orthopedic, gastrointestinal, gynecology, urology, and rheumatology. Due to its chemodenervation effects at the presynaptic nerve terminal, it is useful in treatments of disorders characterized by abnormal inappropriate muscle contractions. Conclusions: BoNT has many clinical applications in several medical specialties. Future studies should focus on any additional indications of BoNT therapy as they arise and on any novel product developments.
... Botulism, for instance, was first recorded in 1735, after the consumption of German sausages, although the etiology was not discovered until 1895; its first neurotoxin was identified in 1944. 1 Many more clostridial diseases and their etiologies have been discovered since then and, more importantly, several vaccines and other preventive methods have been developed and are today commercially available worldwide. 8 Notable progress has been made over the past 2 decades or so in fulfilling conventional and molecular Koch postulates for several clostridial diseases of humans and animals. ...
... (1) It was first described in 1820 by Justinus Kerner to be causative factor of botulism, a fatal disease causing muscle paralysis mostly by inhibition of the release of acetylcholine (motor neurotransmitter). (2)(3)(4) BoNTs set up a seven (A-G) serotypes with different antigenicity due to the difference in the Clostridium botulinum strain. (5) There are 2 more serotypes mentioned by some authors, C2 Type (6) and "H" type which possessed a hybrid-like structure with similarity to type A and F. (7) From the known serotypes, BoNT-A & BoNT-B are used as therapeutics. ...
... Botulism, which was initially coined as sausage poisoning or "Kerner's disease", was first described in a manuscript published in 1822 where Kerner summarized 155 cases of "sausage poisoning" in Germany [70]. Remarkably, he also envisioned the possibility of using this paralyzing poison to treat diseases associated with overactive nervous system symptoms, including muscle hypercontraction and the hypersecretion of body fluids. ...
Article
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Botulinum neurotoxins (BoNTs) are the most potent known toxins, and are therefore classified as extremely harmful biological weapons. However, BoNTs are therapeutic drugs that are widely used and have an increasing number of applications. BoNTs show a high diversity and are divided into multiple types and subtypes. Better understanding of the activity at the molecular and clinical levels of the natural BoNT variants as well as the development of BoNT-based chimeric molecules opens the door to novel medical applications such as silencing the sensory neurons at targeted areas and dermal restoration. This short review is focused on BoNTs’ variability and the opportunities or challenges posed for future clinical applications.
... 4,5 BTX was first used in humans to treat strabismus in 1973 and later its applications were extended to many other conditions such as neurogenic detrusor over-activity, chronic migraine, muscle spasticity, axillary hyperhidrosis and blepharospasm. 6 Furthermore, BTX has been approved in more than 50 countries and become the first-choice nonsurgical procedure for facial rejuvenation since 2000. 7 However, many adverse events have been described such as dry mouth, pain at injection site, tiredness, headache, neck pain or weakness, and eye problems including double vision, blurred vision, decreased eye sight, eyelid ptosis, eyelid swelling, brow ptosis and dry eyes. ...
... The transformation of this life frightening toxin to a medical miracle has taken a long time. Its therapeutic potential was firstly acknowledged by Justinus Kerner in 1817 (Erbguth and Naumann 1999). It was used primarily as an agent meant for musclewaning in order to correct investigational strabismus in monkeys. ...
Chapter
Microbes are ubiquitous in nature, and the tremendous potential of microbes is an unquestionable and unhidden phenomenon. The pharmaceutical aspects of microbial diversity can be judiciously explored for patronizing and safeguarding human health standards. Several studies have unveiled the remarkable wonders which target to prolong and ease the human health by treating pathogenic diseases and by curing different metabolic disorders, thereby sustaining human regime. Generally, the aim of pharmaceutical microbiology is to offer acquaintance and consider the importance of the occurrence of bacteria, yeasts, moulds, viruses and toxins in diverse pharmacological raw materials, products, intermediates and the environs advocating therapeutic construction as well as the microbial regulator of medicinal harvests, manufacturing surroundings and people. Meanwhile, the outline of this functional theme area of microbiology, above the ages, pharmacological microbiology, has advanced and stretched expressively to comprehend numerous other sides, e.g. examination and expansion of novel anti-infective representatives, the use of microbes to perceive mutagenic and oncogenic prospective in medications and the usage of microbes in the production of insulin and various other human growth hormone. An array of bioactive composites sequestered using different approaches have not only exposed prominence in diverse pharmaceutical and biotechnological solicitations but have also augmented the indulgence of mankind in exploring variety of microbiota and targeting their diverse functions and the credulous biology behind their production. The defensible and pecuniary stream of the dynamic pharmaceutical elements is often calmer to accomplish for composites fashioned through microbial fermentation attitudes versus the gardening of slower developing macroorganisms. This article stresses on microbial fabricators and their potential to engender innovative biologically active compounds and their starring role in the simplification of human life.
... The transformation of this life frightening toxin to a medical miracle has taken a long time. Its therapeutic potential was firstly acknowledged by Justinus Kerner in 1817 (Erbguth and Naumann 1999). It was used primarily as an agent meant for musclewaning in order to correct investigational strabismus in monkeys. ...
Chapter
Enzymes are biocatalysts which have a central role in the biochemical, physiological, and metabolic functioning of all the organisms from micro to macro level. These catalytic proteins or metalloproteins have wonderful applications in a number of processes for conversion of substrates to useful products and are used in pharmaceutical, nutraceutical, cosmetic, food and beverage, and other industries. Different sources of these enzymes have been explored for commercial production. The reservoir of microbial world has not been investigated to a greater extent. The microorganisms have proved as an effective source of these industrially important enzymes. The reason for exploring enzymes from microorganisms is their stability at different physiological conditions like high and low temperature, pH, salinity, and others like high catalytic activity and ease of standardization and production. In recent times, the enhancement of production of these microbial enzymes can be achieved using different genetic modulatory methodologies, physiological parameter redesigning, and protein bioengineering. These techniques are the focus of researchers for industrial-friendly hyperproduction of microbial enzymes for generating various formulations.
... Botulinum toxin (BoNT) is a potent poisonous neurotoxin, which is produced by the bacterium Clostridium botulinum and related species [3]. Ingestion of BoNT-poisoned food causes intoxication by inhibiting the release of the neurotransmitter acetylcholine from nerve fibers, thereby inhibiting muscle contractions, which was first described in the early 17th century [4]. BoNT was first isolated in 1895, and now could be classified antigenically and serologically into eight distinguishable exotoxins (A, B, C1, C2, D, E, F, and G) [5]. ...
Article
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OnabotulinumtoxinA (BoNT-A) was first used to treat neurogenic lower urinary tract dysfunction (LUTD) 30 years ago. Recently, application of BoNT-A in LUTD have become more common since the approval of intravesical BoNT-A injection for patients with both overactive bladders (OAB) and neurogenic detrusor overactivity (NDO) by regulatory agencies in many countries. Although unlicensed, BoNT-A has been recommended to treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS) under different guidelines. BoNT-A delivery with liposome-encapsulation and gelation hydrogel intravesical instillation provided a potentially less invasive and more convenient form of application for patients with OAB or IC/BPS. BoNT-A injections into the urethral sphincter for spinal cord injury patients with detrusor-sphincter dyssynergia have been used for a long time. New evidence revealed that it could also be applied to patients with non-neurogenic dysfunctional voiding. Previous studies and meta-analyses suggest that BoNT-A injections for patients with benign prostate hyperplasia do not have a better therapeutic effect than placebo. However, new randomized and placebo-controlled trials revealed intraprostatic BoNT-A injection is superior to placebo in specific patients. A recent trial also showed intraprostatic BoNT-A injection could significantly reduce pain in patients with chronic prostatitis. Both careful selection of patients and prudent use of urodynamic evaluation results to confirm diagnoses are essential for successful outcomes of BoNT-A treatment for LUTD.
... The first scientific description of botulism was made by Dr. Kerner during the Napoleonic war (1795-1813), who described following the ingestion of contaminated meat, vomiting, intestinal spasm, ptosis, strabismus, dysphagia leading to flaccid paralysis respiratory failure. Dr. Kerner even hypothesised that this toxin could be used therapeutically [6]. Botulinum toxin was not isolated until late in the 19th century by Emile Pierre-Marie van Ermengem [7]. ...
Article
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The efficacy of onabotulinumtoxinA (OnaB-A) as a preventative treatment for chronic migraine, emerging fortuitously from clinical observation is now supported by class one evidence and over two decades of real-world clinical data. There is still limited ability to predict a clinically meaningful response to OnaB-A for individual patients, however. This review summarises briefly the proposed mechanism of OnaB-A in chronic migraine, the literature of predictors of clinical response, and recent developments in the field.
... A sharp increase in food poisoning related deaths in Welzheim was attributed to the consumption of blood sausages. After conducting experiments both himself and animals, Kerner deduced that the "sausage poison" 16 and "Fatty poison" because it was observed that illness followed ingestion of spoiled sausage. ...
Book
Botulinum toxin also called “miracle poison” is one of the most poisonous biological substances known. Now a day’s Botox is used in Facial aesthetics treatment to enhance facial contours. Botox is the most effective treatment for smoothing fine lines and reducing wrinkles that appears over time. Botulinum toxin is an ingredient in the spa treatment and has found its way into beauty salons through the medical world. Botox is a powerful muscle relaxant that is used in small doses because it is potent. Botox has different medical uses for ailments such as spasticity and muscle pain. Botulinum toxin was first used clinically in the late 1970s in ophthalmology to treat strabismus, and over the last 20 years has gained widespread use in conditions requiring inhibition of excessive muscle spasm. The broad range of medical indications for Botulinum toxin include treatment of movement disorders (e.g. spasticity, cervical dystonia), urological disorders (e.g. overactive bladder), dermatological conditions (e.g. axillary hyperhidrosis), as well as cosmetic applications. Botulinum toxins usage procedures are the fastest growing area of dentistry with the most significant, minimally invasive, conservative, quick and painless approach with promising results. It provides improved therapeutic and aesthetic outcomes for many clinical situations with ramifications in various branches of dentistry including restorative, aesthetic, periodontics, orthodontics and prosthodontics. It is evident that the use of botulinum toxin in the dental profession has a great potential.
... He described this as the 'fat poison' or 'sausage poison' and even demonstrated its effect by applying on smaller animals. There was paralysis of that group of muscles but showed complete recovery in the next a few days [1]. The toxin of clostridium botulinum was later discovered by Emile Pierre van Ermengemm in 1895 [2] and coined the term Botulus (latin word for sausage). ...
Article
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Botulinum toxin is produced by Clostridium botulini bacteria. It has been increasingly used as a boon in medical practice for chemodenervation in conditions like skeletal muscle spasticity, glandular hypersecretion, neuropathic pain and smooth muscle hyperactivity. The action of Botulinum neurotoxin (BoNT) is by blocking the neurotransmission at the cholinergic nerve endings, by inhibiting the docking and fusion of Acetyl Choline (Ach) vesicles for exocytosis into the synaptic area.Botulinum toxin has been used for management of neurological disorders with great patient satisfaction and appreciation. The effect of botulinum toxin wears off in 3-6 months and may require another dose. Frequent dosing may lead to production of antibodies against BoNT with consequent irresponsiveness to therapy in a few cases. Scrupulous use of botulinum toxin in the hands of experts may help a long way in giving much needed relief and respite to neurological patients and increase their quality of life. Its use in cosmetic dermatology in reducing wrinkles, by relaxing the facial muscles is very popular
... (The word botulism is derived from the Latin botulus, which means sausage). Kerner (1) established that death from poisoning by BT was due to paralysis of muscles, and he was also the first to suggest possible therapeutic use for this toxin. A Belgian microbiologist, Emile-Pierre van Ermengem, first identified the bacterium, Clostridium botulinum, in 1895. ...
... The illness was initially observed in the 17th century in Europe specifically linked to sausages. However, the first complete description of clinical symptoms was published between 1817 and 1822 by the German physician and poet Justinus Kerner (1786-1862), who nicknamed the toxin "sausage poison botulus" based on the Latin "botulus" [7]. The disease was known in Europe during the late 18th century and later was accepted as a foodborne disease throughout the northern hemisphere [8]. ...
Article
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Objectives: The purpose of this study was to analyze epidemiological data concerning foodborne botulism in Western Romania over the last decade. Botulism, the toxin formed by the bacterium Clostridium botulinum, results in a neuroparalytic disorder capable of severe clinical progression that begins in the cranial nerves and progressively descends. Preventing progression to a severe case entails timely diagnosis since curative assets are restricted. Ingesting food containing a preformed toxin (foodborne botulism) is the most typical form. Methods: Medical records were retrospectively analyzed from 2010 to 2020 for all food botulism cases. A seroneutralization test was performed with type A, B and E anti-botulinum sera to establish the kind of toxin involved. Results: Overall, 18 cases of foodborne botulism were admitted to the hospital during this period and confirmed by laboratory analysis. Most of the participants in our study were men (61.1%), and 77.8% of the total lived in rural areas. All the participants showed classic symptoms of botulism, and dysphagia was present in all cases. The trivalent ABE antitoxin was administered by the hospital, and toxin type B was isolated in all patients. The main sources of the toxin were pork, ham and canned pork meat. Conclusions: Stronger efforts are needed to foster community awareness of foodborne botulism, particularly in home-preserved food.
... El tratamiento de un músculo con TBA da como resultado una denervación funcional en dos días y alcanza un pico de efecto después de 4-6 semanas, lo que lleva a la flacidez muscular y a la parálisis. La toxina botulínica se ha utilizado en el tratamiento de afecciones neurológicas, como el blefaroespasmo, la distonía cervical y otras formas de espasticidad miotónica 4,5 . Las indicaciones, sin embargo, se han ampliado y a día de hoy también se utiliza para tratar patologías del espectro de disautonomía nerviosa, hiperhidrosis axilar, sialorrea crónica, la dispareunia, la fisura anal o la acalasia, así como agente analgésico y cosmético. ...
... Botulinum neurotoxins (BoNTs) are produced by anaerobic bacteria of the genus Clostridium and are responsible for the deadly disease called botulism manifested by neuromuscular paralysis (Erbguth and Naumann, 1999;Schiavo et al., 2000;Montecucco and Molgó, 2005). In the last three decades, BoNTs have been utilized widely in many medical applications when injected locally and in small doses (Davletov et al., 2005;Chaddock and Marks, 2006;Foster et al., 2006). ...
Article
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Botulinum neurotoxins (BoNTs) type A and type B are commonly used as biopharmaceutics for neurological diseases, uniquely allowing months-long paralysis of target muscles. Their exquisite neuronal specificity is conferred by a multistep process of binding, internalization, cytosolic escape and cleavage of the neuron-specific proteins, SNAP-25 and vesicle-associated membrane proteins (VAMPs), ultimately to inhibit secretion of neurotransmitters. Currently the mouse lethality bioassay is the only available method for quality control testing of VAMP-cleaving botulinum products. Refined assays for botulinum product testing are urgently needed. Specifically, in vitro replacement assays which can account for all steps of BoNT intoxication are in high demand. Here, we describe a novel SiMa cell-based approach where re-engineering of the VAMP molecule allows detection of all BoNT/B intoxication steps using a luminescent enzymatic reaction with sensitivity comparable to mouse LD50 bioassay. The presented one-step enzyme-linked immunosorbent assay meets 3Rs (replacement, reduction, and refinement of the use of animals) objectives, is user-friendly and will accelerate development of new botulinum drugs. The sensitive enzymatic reporter cell line could also be adapted for the detection of toxin activity during the manufacture of botulinum and tetanus vaccines.
... It was first described in the 1820s by Kerner, who presented a study on several patients suffering from fatal poisoning after ingestion of contaminated sausages. Kerner described in these patients muscular paralysis of respiratory muscles, muscles of the upper and lower limbs, and vegetative disorders such as mydriasis, double vision, and gastrointestinal and bladder disorders [1][2][3]. "Kerner's disease" as it was originally called, later became "botulism" (from the Latin botulus, sausage). The number of cases of foodborne botulism increased around the world during the 19th century, mainly as a result of the consumption of sausages but also due to smoked fish and low-acid preserved vegetables. ...
Article
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Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.
Chapter
This chapter discusses the history of botulinum toxin as a therapeutic option in medicine starting with early observations of Kerner in 1800s on botulism outbreaks and his recognition of the toxin’s potential for medical use, the discovery of the responsible agent by Van Ermengem in late 1800’s and the major contribution of several basic scientists, Edward Schantz, Karl Lamanna, Eric Johnson and others who purified, developed and produced the toxin for clinical use. Finally, the work of Alan Scott who first introduced the toxin for clinical use and neuroscientists such as Fahn, Jankovic, Brin, Tsui, Comella and others who, through their early high quality clinical trials, found diverse indications for botulinum toxin therapy in clinical medicine are discussed.
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Foodborne botulism is a life-threatening disease caused by the ingestion of food containing preformed botulinum neurotoxins, the most potent natural poisons known to humans. On the basis of the new challenges in management of the diseases as well as considering the potential use of botulinum toxins as biological weapons, foodborne botulism is still considered a public health emergency. Each suspected case should be immediately notified to public health authorities with the aim of preparing a prompt response. With the aim of improving botulism surveillance systems, health authorities as well as governmental organizations should enhance national and international cooperation. Education and training activities devoted to operators involved in the disease management, and to general population, may significantly contribute to strengthen the system.
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Cambridge Core - Neurology and Clinical Neuroscience - Treatment of Dystonia - edited by Dirk Dressler
Chapter
Botulinum toxin is the ultimate example of the core principle in toxicology that all substances are poisons, and it is only the dose that determines if a substance is therapeutic or toxic. Two forms of pharmaceutical products, onabotulinum toxin A (Botox) and rimabotulinum toxin B (Myobloc), are used as injectable therapeutic agents to induce local muscle paralysis to treat a growing variety of disorders from dystonia to bladder spasm, as well as cosmetic enhancer to flatten facial wrinkles. More botulinum-based products for these, and other, purposes are under development. As a toxin, botulinum, when ingested, is one of the most lethal on a weight per kilogram basis with a LD50 of 0.001 ug/kg [1].
Article
Botulinum toxin has gained immense popularity since its introduction for therapeutic use. It is used in a variety of movement disorders like hemi-facial spasm, focal dystonias like blepharospasm, cervical dystonia, oromandibular dystonia, limb dystonias. It is also being used in patients with tremors, tics and for a variety of indications in Parkinson's disease as well. There are eight subtypes of toxins available, but type A and B are the ones used in movement disorder clinics. The toxin mainly acts by inhibiting the release of acetylcholine at the neuromuscular junction and causing weakness. Type B toxin has more effect over the autonomic nervous system and hence is preferred for hyper-secretory disorders. The use of electromyography and ultrasound further improve the accuracy of the procedure. It is a relatively safe therapeutic option with its effect lasting for around three months. It has very few side effects. The key is to start with the lowest possible dose and then gradually increase the dose depending upon the patient's response. Selecting the right muscles for injection is of utmost importance and is guided by the knowledge of anatomy of the muscles.
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Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in disease and their importance as a class of targets has amplified interest in the development of new strategies to develop inhibitors and ultimately useful drugs. In this Review, we provide a broad overview of several drug discovery efforts focused on metalloenzymes and attempt to map out the current landscape of high-value metalloenzyme targets.
Article
Background: Neurogenic bladder is one of the serious, disturbing problems referred to pediatric urologic clinics. The increase in bladder pressure may damage the upper urinary tract. Anticholinergic medications have been used as the first line of complementary treatment. Regardless can be omitted, botulinum toxin (BT) was introduced as an alternative method for increasing bladder compliance. BT is a neurotoxic poison that can interfere with acetylcholine release, leading to reduced external sphincter pressure and detrusor activity. This study was established to assess urodynamic changes following BT injection among Iranian pediatric population, for the first time. Methods: This clinical trial was conducted at Shahid Beheshti University of Medical Sciences (SBUM), Tehran, Iran, from November 2018 to January 2019 as a medical graduation dissertation. Twenty patients, previously as followings with a neurogenic bladder who met the eligibility criteria, underwent BT injection with general anesthesia using a rigid cystoscope and an endoscopic needle. Demographic data, history of anticholinergic consumption, side effects or intolerance, and the dosage of the injected BT were all recorded. The urodynamic variables during our study included: flow rate in second two, the flow time of diuresis, time of peak flow, average flow, discharged volume, maximum detrusor muscle filling pressure, maximum flow, acceleration, post-void residual volume, compliance, and cystometric bladder capacity. SPSS software version 22 was used to analyze data. The significance level was considered less than 0.05. Results: Twenty patients who did not respond to anticholinergic medications or could not tolerate the side effects were entered the study. The mean age was 7.7 ± 2.02 years (range 5-13), and 13 (65%) of them were male. All patients received anticholinergic medications before BT injection. Discharge volume and maximum detrusor muscle filling pressure showed the most significant changes after injection (p < 0.005). However, there was no significant effect of the baseline characteristics on post-injection improvement in urodynamic results (p > 0.05). Conclusion: In this study, maximum detrusor filling pressure and discharge volume were both significantly improved. These findings motivate additional studies towards selecting better indexes for defining the clinical improvement and its relation with specific urodynamic results. Level of evidence: Treatment study, level III.
Chapter
Botulinum Toxin (BoNT) is an exotoxin derived from Clostridium botulinum, an anaerobic Gram‐positive bacterium. In 1991, a pharmaceutical company called Allergan bought the research findings and renamed the agent as Botox. The first series of cases about BoNT poisoning was published in 1817 by J Kerner. BoNTs are biologic pharmaceuticals and can elicit an immune response like all foreign proteins. In hyperhidrosis, botox blocks the release of acetylcholine and a number of other neurotransmitters from presynaptic vesicles by deactivating SNARE proteins. BoNT appears to be an effective nonsurgical alternative for the treatment of resistant cases of Hailey‐Hailey disease involving large body surface areas. It has also been studied as a potential treatment option for headache and migraine. BoNT is emerging as a revolutionary treatment for many cosmetic and noncosmetic indications.
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Abstract Antibiotic resistance genes (ARGs) are ubiquitous among microorganisms living in a wide variety of environments and can be detected by several molecular techniques. Similarly, toxins and genes encoding toxins are also widespread among organisms. Bacteriophages are bacterial viruses found wherever bacteria exist, and their concentration is particularly high in aquatic environments. The age of the “omics” truly revolutionized this field, establishing the phylogenetic affiliation and function of phages, as well as the role they play in microbial communities and horizontal transfer of bacterial genes. Genomics, transcriptomics, proteomics, and metabolomics have highlighted the role of phages and their interaction with bacterial populations. It is now generally accepted that horizontal gene transfer regularly occurs between bacteriophages and their hosts, either by generalized or specialized transductions or possibly by controlling certain bacterial populations of donors or recipients. This means that phages not only play a major role driving bacterial evolution but also influence their own evolution. Phage infection can result in the bacterial host quickly acquiring (or loosing) novel genes and thus biochemical properties, a process otherwise extremely slow that usually requires long periods of time. This chapter will focus on the role of bacteriophages in the transfer of both antibiotic resistance genes and genes encoding novel toxins to new bacterial species. This knowledge is essential not only to understand the current challenges experienced in medicine but also to prevent, or at least lessen, future clinically relevant threats resulting from gene transfer between microorganisms
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Botulinum toxin is one of the most potent and deadliest substances on earth. Because of its unique mechanism of action at the synaptic junction and the ability to precisely deliver the toxin locally to where it is needed, botulinum toxin has been used as an effective treatment for a plethora of diseases from head to foot, from chronic migraine to ankle spasticity. Unlike systemic drugs, botulinum toxin is delivered by injection to the site of disease. As we will see from the history of botulinum toxin, the ability to deliver the drug locally to minimize the amount of botulinum toxin needed and thereby minimizing systemic exposure has been key to its medical utility. Botulinum toxin was first approved by the US Food and Drug Administration in 1989 for the treatment of blepharospasm and strabismus, but the history starts long before this, with outbreaks of food poisoning in the tenth century. Importantly, the development of botulinum toxins for medical use continues today with the engineering of novel toxins to treat disease.
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Facial aging involves volumetric change, alteration of tissue quality, and the effects of long-standing facial muscular animation. These factors lead to soft tissue ptosis and static and dynamic rhytids. The traditional conept of beauty involves the “triangle of beauty” with high cheekbones and a defined jaw, whereas the “reverse triangle” or pyramid with flattened cheeks, drooping eyes, and jowling is considered unattractive. Facial rhytids can be classified as dynamic or static. Dynamic rhytids occur with muscle action and are best treated by specifically targeting facial muscles with botulinum toxin.
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Cancer is the leading cause of deaths worldwide, though significant advances have occurred in its diagnosis and treatment. The development of resistance against chemotherapeutic agents, their side effects, and non-specific toxicity urge to screen for the novel anticancer agent. Hence, the development of novel anticancer agents with a new mechanism of action has become a major scientific challenge. Bacteria and bacterially produced bioactive compounds have recently emerged as a promising alternative for cancer therapeutics. Bacterial anticancer agents such as antibiotics, bacteriocins, non-ribosomal peptides, polyketides, toxins, etc. These are adopted different mechanisms of actions such as apoptosis, necrosis, reduced angiogenesis, inhibition of translation and splicing, and obstructing essential signaling pathways to kill cancer cells. Also, live tumor-targeting bacteria provided a unique therapeutic alternative for cancer treatment. This review summarizes the anticancer properties and mechanism of actions of the anticancer agents of bacterial origin and antitumor bacteria along with their possible future applications in cancer therapeutics.
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Botulinum toxins are a large family of proteins produced by a gram-positive anaerobic bacterium, Clostridium botulinum. They are largely used in the clinical practice to treat a number of pathologic conditions characterized by the spasticity of striated muscles. Moreover, the neurotoxin is also used, in an off label setting, in the treatment of pain related disorders, such as chronic pelvic pain. Interstitial cystitis/bladder painful syndrome, category III, nonbacterial chronic prostatitis/chronic pelvic pain syndrome, vaginismus and vulvodynia, are actually fields of application and research of botulinum toxins in the affected patients. Some robust evidences exist on the efficacy and safety of botulinum toxin type A in patients affected by interstitial cystitis/bladder painful syndrome, but no consistent data are available on the use of the neurotoxin in the other pelvic pain conditions. To date, there is the urgent need to have adequate randomized, controlled studies to definitively establish the role of botulinum toxins in treating pelvic pain conditions.
Article
Botulinum neurotoxin (BoNT) is an effective treatment for many neurologic disorders. This article gives a comprehensive overview of the clinical applications of BoNT across the field of neurology.
Article
Botulinum neurotoxins (BoNTs) produced by soil bacterium Clostridium botulinum are cause of botulism and listed as biohazard agents, thus rapid screening assays are needed for taking the correct countermeasures in a timely fashion. The gold standard method relies on the mouse lethality assay with a lengthy analysis time, i.e., 2-5 days, hindering the prompt management of food safety and medical diagnosis. Herein, we propose the first paper-based antibody-free sensor for reliable and rapid detection of BoNT/A and BoNT/C, exploiting their cleavage capability toward a synthetic peptide able to mimic the natural substrate SNAP-25. The peptide is labelled with the electroactive molecule methylene blue and immobilized on the paper-based electrode modified with gold nanoparticles. Because BoNT/A and BoNT/C can cleave the peptide with the removal of methylene blue from electrode surface, the presence of these neurotoxins in the sample leads to a signal decrease proportional to BoNT amount. The biosensor developed with the selected peptide and combined with smartphone assisted potentiostat is able to detect both BoNT/A and BoNT/C with a linearity up to 1 nM and a detection limit equal to 10 pM. The applicability of this biosensor was evaluated with spiked samples of orange juice, obtaining recovery values equal to 104 ± 6 % and 98 ± 9% for 1 nM and 0.5 nM of BoNT/A, respectively.
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Botulinum toxin is the most common cosmetic procedure performed in the United States. Botulinum toxin A is well known for its use in the cosmetic world to reduce wrinkles, but its new and emerging use in the treatment of depression offers a novel adjuvant to improve the mood of patients with major depressive disorder. In this chapter, the authors discuss the novel role of botulinum toxin injections in the treatment of depression with a case study. The behavioral theory and the facial feedback hypothesis highlight the intricate pathophysiology of depression as well as the social influence on the course of this disease. Understanding the inhibition of muscle contraction as the pathophysiologic mechanism has allowed botulinum toxin to be developed into a treatment option used in medical settings for a variety of disorders.
Chapter
Most central nervous system (CNS) pathogens infect the nervous system nonspecifically, and disease is the result of the brain’s immune response. This is exemplified by viral and bacterial meningitis, which cause extensive inflammation of the brain or its coverings. However, some pathogens show neural tropism and specifically infect certain neurons, as illustrated by motor neuron infections underlying poliomyelitis, neurosyphilis, or infection of sensory neurons by herpes simplex. Similarly, infestation of the brain by larvae (cysticerci) from intestinal tapeworms nonspecifically causes neurological disease in millions of people in the developing world, whereas rare paralytic amoeba actively invade the brain through the nasal canal and feast on brain tissue. By far the most important neurological disease caused by a pathogen is neuro-acquired immunodeficiency syndrome (AIDS), the development of cognitive decline and dementia in the late stages of AIDS due to brain infection with the human immunodeficiency virus. Given the magnitude of the global AIDS endemic, these cases will soon rival more traditional age-related dementia. Neuroscientists are unlikely to contribute to the development of more effective treatments, a task that rests on microbiologists and immunologists who do develop vaccines and antivirals. However, several neurotoxins (Botox) and neurotropic viruses (herpes simplex virus 1) are providing tools to treat neurological disease through targeted delivery of genes or paralytic therapeutics.
Chapter
Botulinum toxin is the ultimate example of the core principle in toxicology that all substances are poisons, and it is only the dose that determines if a substance is therapeutic or toxic. Two forms of pharmaceutical products, onabotulinum toxin A (Botox) and rimabotulinum toxin B (Myobloc), are used as injectable therapeutic agents to induce local muscle paralysis to treat a growing variety of disorders from dystonia to bladder spasm, as well as cosmetic enhancer to flatten facial wrinkles. More botulinum-based products for these, and other, purposes are under development. As a toxin, botulinum, when ingested, is one of the most lethal on a weight per kilogram basis with a LD50 of 0.001 ug/kg [1].
Article
Full-text available
Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a potential biological weapon and an effective therapeutic drug for involuntary muscle disorders. The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined at 3.3 Å resolution. The structure reveals that the translocation domain contains a central pair of helices 105 Å long and a ~50 residue loop or belt that wraps around the catalytic domain. This belt partially occludes a large channel leading to a buried, negative active site — a feature that calls for radically different inhibitor design strategies from those currently used. The fold of the translocation domain suggests a mechanism of pore formation different from other toxins. Lastly, the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.
Article
Full-text available
Achalasia is a disorder of swallowing in which the lower esophageal sphincter fails to relax. We report the use of botulinum toxin, a paralytic agent, for the treatment of this condition. In a double-blind trial, 21 patients with achalasia received either 80 units of botulinum toxin or placebo, injected endoscopically into the lower esophageal sphincter. One week later, the response to treatment was assessed on the basis of changes in the symptom scores (measured on a scale from 0 to 9), pharyngoesophagograms, and results of esophageal manometric and scintigraphic studies. Patients who received placebo initially were subsequently treated with botulinum toxin. After six months, esophageal scintigraphy was repeated. One week after treatment, the mean decrease in the symptom score was 5.4 points for the patients treated with botulinum toxin and 0.5 point for the placebo group (P = 0.001). The mean decrease in the pressure of the lower esophageal sphincter was 33 percent in the treatment group, as compared with a mean increase of 12 percent in the placebo group (P = 0.02), and the mean increase in the width of the opening of the lower esophageal sphincter was 204 percent in the treatment group, as compared with a mean decrease of 14 percent in the placebo group (P = 0.02). Nineteen of the 21 patients treated with botulinum toxin had symptomatic improvement initially; after six months 14 patients were still in remission. This improvement was accompanied by a decrease in esophageal retention that was sustained at six months (46 percent, as compared with a pretreatment value of 77 percent; P = 0.04). There were no serious adverse effects. Injection of botulinum toxin into the lower esophageal sphincter is an effective, safe, and simple method of treatment for achalasia, with results that are sustained for several months.
Article
Objective To evaluate the effect of intracutaneous injections of botulinum toxin type A on excessive focal hyperhidrosis.Design Therapeutic before-and-after trial over 4 months.Setting Neurological and dermatological university departments.Patients Eleven patients with excessive axillary, palmar, or plantar hyperhidrosis fulfilling the following criteria: (1) local and systemic drug therapy had failed to improve their symptoms; (2) the patients were severely disabled with respect to their occupation and social activities; and (3) a successful treatment by botulinum toxin would obviate the need for destructive surgical procedures.Interventions Three mouse units of botulinum toxin (Botox) per 4-cm2 skin area was injected intracutaneously in 16 axillae, 8 palms, and 2 soles.Main Outcome Measures Reduction of hyperhidrosis as documented by the Minor iodine-starch test and gravimetrical assessment of local spontaneous sweat production measured over 1 minute.Results In all patients, botulinum toxin completely abolished sweating in the injected areas (P<.001) within 3 to 7 days. No relevant adverse effects occurred and no clinical recurrence of hyperhidrosis was observed within the follow-up period of up to 5 months. Occasionally, subclinical reactivation of sweat gland function was observed 4 months after treatment.Conclusions Intracutaneous botulinum toxin seems preferable to any hitherto used conservative or surgical procedures and may become the therapy of choice in pathological focal hyperhidrosis.
Article
BOTULISM had been recognized by the 18th century, but the observation that a toxin produced by an anaerobic organism might be responsible for food poisoning was not made until 1897.1 Although seven immunologically distinct toxins have since been identified, only types A, B, and E have been linked to cases of botulism in humans.2 , 3 Botulinum toxin type A (hereafter referred to as botulinum toxin), one of the most lethal biologic toxins, has been found to be of therapeutic value in the treatment of a variety of neurologic and ophthalmologic disorders.4 The Food and Drug Administration recently approved botulinum toxin (Oculinum) . . .
Article
We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions.
Article
Rhesus monkeys were used to evaluate the effect of various neurotoxic agents after injection into extraocular muscles in an attempt to seek correction of strabismus. DFP was too toxic. A bungarotoxin was of too limited duration. Botulinum, Type A injected into the horizontal rectus muscles of rhesus monkeys produced prolonged paresis of the injected muscle without serious local side effects: duration extended from 2 wk to permanent, depending on the dose injected. The clinical value awaits human trial. It could be used to replace or augment surgical correction of stabismus and in reducing lid retraction in endocrine exophthalmos. (Barnshaw - Camden, N.J.).
One hundred thirty-two doses of botulinum A toxin were injected into 42 humans. The effect on horizontal strabismus was uniformly beneficial, and effect lasting up to 411 days since the last injection was documented. The effect in vertical strabismus and lid retraction was beneficial, but less strongly so. No systemic effect or local complications were encountered except for effect on adjacent muscles. The drug appears to be a safe and useful therapy for strabismus.
Article
Neurotransmitter release is potently blocked by a group of structurally related toxin proteins produced by Clostridium botulinum. Botulinum neurotoxin type B (BoNT/B) and tetanus toxin (TeTx) are zinc-dependent proteases that specifically cleave synaptobrevin (VAMP), a membrane protein of synaptic vesicles. Here we report that inhibition of transmitter release from synaptosomes caused by botulinum neurotoxin A (BoNT/A) is associated with the selective proteolysis of the synaptic protein SNAP-25. Furthermore, isolated or recombinant L chain of BoNT/A cleaves SNAP-25 in vitro. Cleavage occurred near the carboxyterminus and was sensitive to divalent cation chelators. In addition, a glutamate residue in the BoNT/A L chain, presumably required to stabilize a water molecule in the zinc-containing catalytic centre, was required for proteolytic activity. These findings demonstrate that BoNT/A acts as a zinc-dependent protease that selectively cleaves SNAP-25. Thus, a second component of the putative fusion complex mediating synaptic vesicle exocytosis is targeted by a clostridial neurotoxin.
Article
The inhibitory action of botulinum toxin is not confined to the neuromuscular junction. The toxin has long been known to block all the autonomic cholinergic fibers, including the major secretomotor parasympathetic fibers to salivary glands. The parotids are the largest of the salivary glands and their selective chemodenervation with botulinum toxin A is likely to result in substantial reduction of saliva production. Injection of the parotid glands with botulinum toxin is proposed as an new treatment for sialorrhea in patients with amyotrophic lateral sclerosis and other neurological diseases.
Article
Gustatory sweating is an autonomic disorder that frequently occurs after parotid gland surgery. We investigated the action of intracutaneous injections of botulinum toxin (BTX) (1.0-2.0 mouse units/2.25-cm2 skin area) in 45 patients (mean age, 52 years) with gustatory sweating. The area of hyperhidrosis was determined by Minor's iodine test before and up to 24 weeks after the injection. The effect of BTX was assessed by measuring the hyperhidrotic area. The maximum BTX-induced reduction of gustatory sweating was seen at 7.4 +/- 4.5 days after injection. The area of sweating decreased from 17.6 +/- 8.6 cm2 before BTX to 1.3 +/- 1.6 cm2 after BTX (p < 0.0001). Half the patients rated gustatory sweating subjectively as completely abolished, and the remainder felt pronounced improvement. No toxic effects were observed. In none of the patients did hyperhidrosis recur over a 6-month follow-up. We conclude that BTX is a safe and effective treatment that can be recommended as the therapy of choice in gustatory sweating.
Article
otulinum neurotoxin A (BoNT/A) has become a valuable tool in the treatment of neu- rological disorders associated with increased muscle tone and has revolutionized the treatment of dystonia and focal spasticity. It acts at cholinergic nerve terminals by cleav- ing SNAP-25, a protein involved in the fusion of synaptic vesicles with the presynaptic membrane. 1 Cholinergic autonomic parasympathetic and postganglionic sympathetic nerve syn- apses are also amenable to treatment with botulinum toxin. Within the last few years, an increasing number of articles have been published fo- cusing on new applications for BoNT/A. This short review gives an overview on re- cent indications of BoNT/A in the treat- ment of disorders of the autonomic ner- vous system and an outlook on possible future application.
Justinus Kerners Beitrag zur Erforschung des Botulismus
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ber einen neuen anaeroben Bacillus und seine Beziehung zum BotulismusEnglish translation: Classics in infectious diseases: a new anaerobic bacillus and its relation to botulism
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Die ersten systematischen Beschreibungen und tierexperimentellen Untersuchungen des Botulismus. Zum 200 Geburtstag von Justinus Kerner am 18 September 1986
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Wurstkerner Justinus Kerners Beitrag zur Erforschung des Botulismus
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Grü sser OJ. Der " Wurstkerner. " Justinus Kerners Beitrag zur Erforschung des Botulismus. In: Schott H, ed. Justinus Kerner als Arzt und Seelenforscher. 2nd ed. Verlag Nachrichtenblatt der Stadt Weinsberg: 1998:232–257.
Romantische Naturphilosophie in der a ¨ rztlichen Praxis
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Schott H. Romantische Naturphilosophie in der a ¨ rztlichen Praxis. In: Schott H, ed. Meilensteine der Medizin. Dortmund: Harenberg Verlag, 1996:318 –325.
Die ersten systematischen Beschreibungen und tierexperimentellen Untersuchungen des Botulismus. Zum 200. Geburtstag von Justinus Kerner am
  • Oj Grü Sser
Grü sser OJ. Die ersten systematischen Beschreibungen und tierexperimentellen Untersuchungen des Botulismus. Zum 200. Geburtstag von Justinus Kerner am 18 September 1986. Sudhoffs Arch 1987;10:167–187.